Supplementation of Oral Reduced Glutathione in Pediatric Cystic Fibrosis Patients

• Sponsor: Clark Bishop (Other)
• Overall Status: Completed
• CT.gov ID: NCT02029521
• Collaborator: (none)
• Enrollment: 47
• Location: 1
• Arms: 2
• Duration (Months): 16
• Patients Per Site Per Month: 2.9

Study Details

Study Description

Brief Summary

Many individuals with cystic fibrosis experience growth failure. The reasons are not clear, but inflammation of the gut in these patients seems to be one important reason. Glutathione is important to normal function of the intestine and lungs. Glutathione functions to decrease inflammation and to thin mucus. However, in cystic fibrosis, glutathione gets trapped inside of cells, so it cannot travel to the surface of the cells and perform its proper function. Moreover, glutathione has been shown to improve nutritional status in patients with AIDS and cancer.

Investigators hypothesize that supplementation of oral glutathione to pediatric individuals with cystic fibrosis could improve growth failure.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Dietary Supplement: Oral reduced l-glutathione; Dietary Supplement: Placebo	N/A

Detailed Description

Cystic fibrosis (CF) is known principally for its pulmonary consequences. However, for most individuals with CF, the earliest manifestations are not pulmonary, but gastro-intestinal. Many children experience growth failure. Chronic gut inflammation also develops. Research has also established that lung function scores are significantly correlated with Body Mass Index (BMI) and weight percentile in CF. Therefore, interventions to improve the gastro-intestinal dimension of CF in early childhood have the potential to ameliorate the course of the disease over the life span of the patient. Both Cochrane Database reviews and a recent review commissioned by the Cystic Fibrosis Foundation found only fair evidence for current nutritional guidelines.Therefore, there is a pressing need for a treatment for CF growth failure that is more effective and less invasive than current treatments.

The discovery that CF is associated with significantly diminished efflux of reduced glutathione (GSH) from most cells in the body offers a new perspective on the pathophysiology of this disease. GSH plays several important roles; among the most important are the following: 1) primary water-soluble antioxidant; 2) mucolytic capable of cleaving disulfide bonds; and 3) regulator of immune system function. The relationship between redox ratio (GSH:GSSG) and total glutathione (GSH+GSSG) and the initiation of inflammation is well established in the research literature.

GSH is also an important component of the epithelial lining fluid of the intestines, helping to keep intestinal mucus thin, serving to defend the intestinal system against reactive oxygen species, and keeping inflammation in check under normal circumstances. GSH is an FDA-approved treatment for AIDS-related cachexia. The growing recognition of GSH system dysfunction in CF, coupled with an established research literature on the role of GSH in gastro-intestinal function and weight gain in non-CF contexts, suggest a new intervention for growth failure in early childhood in CF patients. Specifically, investigators hypothesized that oral glutathione could effectively treat CF growth failure in pediatric patients.

Study Design

• Study Type: Interventional
• Actual Enrollment: 47 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Supplementation of Oral Reduced Glutathione in Pediatric Cystic Fibrosis for Growth Failure
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Mar 1, 2012
• Actual Study Completion Date: Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oral reduced l-glutathione The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg.	Dietary Supplement: Oral reduced l-glutathione; The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Placebo Comparator: Placebo Calcium Citrate The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	Dietary Supplement: Placebo; calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.

Outcome Measures

Primary Outcome Measures

1. Weight Percentile at 3 Months [3 months]

   Weight Percentile at 3 months adjusted for sex and age

2. Height Percentile [3 months]

   Height Percentile adjusted for sex and age

3. BMI Percentile [3 months]

   Body Mass Index percentile adjusted for sex and age. Standard BMI are not available for participants under 2 years of age

4. BMI Percentile [6 months]

   Body Mass Index percentile adjusted for sex and age. Not available for participants under 2 years of age.

5. Weight Percentile [6 months]

   Weight percentile, adjusted for sex and age

6. Height Percentile [6 Months]

   The subjects were measured over the course of the study to determine if treatment improved height percentile.

7. Fecal Calprotectin [6 months]

   Fecal Calprotectin, a measure of gut inflammation, was measured to see if the treatment decreased this outcome.

Secondary Outcome Measures

1. Forced Vital Capacity [3 months]

   Forced vital capacity percent predicted

2. FEV1 [3 months]

   Forced expiratory volume at one second, percent predicted

3. Bacteriology [3 months]

   Expectorated sputum or throat swab

4. Forced Vital Capacity [6 months]

   Percent predicted of forced vital capacity.

5. FEV1 [6 months]

   Forced expiratory volume at one second, percent predicted.

6. C-Reactive Protein (CRP) [6 months]

   CRP was measured to determine if this test fell during the course of treatment.

7. White Blood Cell Count [6 months]

   White blood cell count was measure at the beginning and end of the study to determine if treatment affected this test.

8. Vitamin E [6 months]

   Serum Vitamin E levels were measured to determine if treatment affected this test.

9. Alanine Aminotransferase (ALT) [6 Months]

   ALT was measured to determine if liver function was affected by treatment over the course of the study.

10. Bacteriology [6 Months]

    Expectorated sputum or throat swab

11. Frequency of Abdominal Pain [6 months]

    Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent

12. Severity of Abdominal Pain [6 months]

    Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe

13. Frequency of Belching [6 months]

    Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent

14. Severity of Belching [6 months]

    Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe

15. Frequency of Flatulence [6 months]

    Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent

16. Severity of Flatulence [6 months]

    Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe

17. Frequency of Lack of Appetite [6 months]

    Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent

18. Severity of Lack of Appetite [6 months]

    Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe

19. Frequency of Bloating [6 months]

    Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent

20. Severity of Bloating [6 months]

    Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe

21. Frequency of Nausea [6 months]

    Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent

22. Severity of Nausea [6 months]

    Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe

23. Frequency of Vomiting [6 months]

    Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent

24. Severity of Vomiting [6 months]

    Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe

25. Frequency of Heart Burn [6 months]

    Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent

26. Severity of Heart Burn [6 months]

    Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe

27. Frequency of Diarrhea [6 months]

    Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent

28. Severity of Diarrhea [6 months]

    Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe

29. Frequency of More Than 2 Bowel Movements Per Day [6 months]

    Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent

30. Severity of More Than 2 Bowel Movements Per Day [6 months]

    Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe

31. Frequency of Less Than 2 Bowel Movements Per Week [6 months]

    Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent

32. Severity of Less Than 2 Bowel Movements Per Week [6 months]

    Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Months to 10 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

-Diagnosis of Cystic Fibrosis by either of the following criteria: >60 sweat chloride test or paired deleterious DNA cystic fibrosis transmembrane conductance regulator (CFTR) mutations (Ambry genetics, Genetech or ARUP);

-Pancreatic insufficient as defined by doctor's prescription of pancreatic enzymes.

Exclusion Criteria:

• Hospitalized for bowel obstruction or surgery in the six months prior to enrollment;

• had had a pulmonary exacerbation or oral steroid use or IV antibiotics within one month of enrollment,

• who had been taking either GSH or N-acetyl cysteine (NAC) within the 12 month period immediately prior to the trial,

• chronically infected with Burkholderia cepacia.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Turin		Italy

Sponsors and Collaborators

• Clark Bishop

Investigators

• Study Director: Clark T Bishop, MD, Intermountain Health Care

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Clark Bishop, Co investigator, Brigham Young University
• ClinicalTrials.gov Identifier: NCT02029521
• Other Study ID Numbers: FIMP/clin.stud/2010/1.
• First Posted: Jan 8, 2014
• Last Update Posted: Feb 8, 2016
• Last Verified: Jan 1, 2016

• Keywords provided by Clark Bishop, Co investigator, Brigham Young University: cystic fibrosis; growth Failure; glutathione
• Additional relevant MeSH terms: Cystic Fibrosis; Fibrosis

Study Results

Participant Flow

Arm/Group Title	Oral Reduced L-glutathione	Placebo Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. Oral reduced l-glutathione: The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Period Title: Overall Study
STARTED	24	23
COMPLETED	22	22
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	Oral Reduced L-glutathione	Placebo Oral Calcium Citrate	Total
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	Total of all reporting groups
Overall Participants	22	22	44
Age, Customized (participants) [Number]
15 months to 3 years	6 27.3%	6 27.3%	12 27.3%
3 years to 10 years	16 72.7%	16 72.7%	32 72.7%
Sex: Female, Male (Count of Participants)
Female	14 63.6%	10 45.5%	24 54.5%
Male	8 36.4%	12 54.5%	20 45.5%
Region of Enrollment (participants) [Number]
Italy	22 100%	22 100%	44 100%
Body Mass Index Percentile (Percentile adjusted for age and sex) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentile adjusted for age and sex]	25.1 (15.9)	31.1 (14.1)	28.3 (15.1)
Weight Percentile (Percentile adjusted for sex and age) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentile adjusted for sex and age]	24.2 (13.7)	33.5 (13.4)	26.9 (13.6)
Height Percentile (Percentile adjusted for weight and heigh) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentile adjusted for weight and heigh]	36.3 (14.4)	39.3 (13.5)	37.7 (13.9)
Fecal Calprotectin (micrograms/gram feces) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [micrograms/gram feces]	113.2 (52.5)	76.1 (32.2)	94.6 (47)
Forced Expiratory Volume at one second. (Percent predicted) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percent predicted]	63.5 (4.8)	71 (7.8)	66.9 (7.3)
Forced Vital Capacity (Percent Predicted) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percent Predicted]	81.8 (8.7)	88.2 (9.6)	84.7 (9.4)
Gene Mutations (participants) [Number]
G551D/1303K	1 4.5%	0 0%	1 2.3%
DelF508/R117H	1 4.5%	0 0%	1 2.3%
R117H/G542X	1 4.5%	2 9.1%	3 6.8%
DelF508/DelF508	4 18.2%	5 22.7%	9 20.5%
DelF508/R553X	2 9.1%	0 0%	2 4.5%
W1282X/R347P	1 4.5%	0 0%	1 2.3%
DelF508/N1303K	1 4.5%	1 4.5%	2 4.5%
DelF508/3849+10KBCT	1 4.5%	1 4.5%	2 4.5%
G551D/621+1GT	1 4.5%	0 0%	1 2.3%
W1282X/DelF508	2 9.1%	1 4.5%	3 6.8%
R117H/R347P	1 4.5%	1 4.5%	2 4.5%
R117H/W1282X	1 4.5%	0 0%	1 2.3%
DelF508/G542X	1 4.5%	2 9.1%	3 6.8%
3849+10kb/N1303k	1 4.5%	0 0%	1 2.3%
N1303K/R553X	1 4.5%	0 0%	1 2.3%
G551D/DelF508	1 4.5%	2 9.1%	3 6.8%
R117H/1466delAATT	1 4.5%	0 0%	1 2.3%
DelF508/G576X	0 0%	1 4.5%	1 2.3%
DelF508/S489X	0 0%	1 4.5%	1 2.3%
G542X/G542X	0 0%	1 4.5%	1 2.3%
DelF508/R347P	0 0%	1 4.5%	1 2.3%
R117H/R117H	0 0%	1 4.5%	1 2.3%
N1303k/G542X	0 0%	2 9.1%	2 4.5%
Sweat Chloride Test (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	87.7 (15.8)	85.0 (15.6)	86.3 (15.6)
Participants' Lipase Intake in Units Per Day (units of lipase) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units of lipase]	130909.1 (54590.2)	123181.8 (47044.7)	127045.5 (50512.7)
Bacteriology (participants) [Number]
A. xylososidans	3 13.6%	1 4.5%	4 9.1%
MRSA	0 0%	1 4.5%	1 2.3%
PA	2 9.1%	3 13.6%	5 11.4%
Staph	7 31.8%	9 40.9%	16 36.4%
Normal flora	3 13.6%	2 9.1%	5 11.4%
PA and S. maltophilia	1 4.5%	0 0%	1 2.3%
PA and Staph	5 22.7%	6 27.3%	11 25%
Staph and A. xylososidans	1 4.5%	0 0%	1 2.3%
White Blood Cell Count (1000 cells/mm^3) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [1000 cells/mm^3]	9.1 (2.0)	8.9 (2.7)	9.0 (2.4)
ALT (units per liter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units per liter]	23.2 (9.3)	22.6 (11.4)	22.9 (10.3)
Vitamin E (micrograms per ml.) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [micrograms per ml.]	7.7 (1.6)	7.5 (1.6)	7.6 (1.6)
C-Reactive Protein (miligrams per liter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [miligrams per liter]	13.3 (7.7)	12.1 (6.6)	12.7 (7.1)
Frequency of Abdominal Pain (participants) [Number]
1- never	7 31.8%	11 50%	18 40.9%
2- rare	10 45.5%	4 18.2%	14 31.8%
3- frequently	4 18.2%	6 27.3%	10 22.7%
4- constantly	1 4.5%	1 4.5%	2 4.5%
Severity of Abdominal Pain (participants) [Number]
1- absent	6 27.3%	11 50%	17 38.6%
2- light	12 54.5%	4 18.2%	16 36.4%
3- moderate	3 13.6%	7 31.8%	10 22.7%
4- serious	1 4.5%	0 0%	1 2.3%
Frequency of Belching (participants) [Number]
1- never	14 63.6%	15 68.2%	29 65.9%
2- rare	3 13.6%	3 13.6%	6 13.6%
3- frequently	5 22.7%	4 18.2%	9 20.5%
4- constantly	0 0%	0 0%	0 0%
Severity of Belching (participants) [Number]
1- absent	14 63.6%	3 13.6%	17 38.6%
2- light	5 22.7%	10 45.5%	15 34.1%
3- moderate	3 13.6%	8 36.4%	11 25%
4- serious	0 0%	1 4.5%	1 2.3%
Frequency of Flatulence (participants) [Number]
1- never	3 13.6%	4 18.2%	7 15.9%
2- rare	10 45.5%	9 40.9%	19 43.2%
3- frequently	8 36.4%	9 40.9%	17 38.6%
4- constantly	1 4.5%	0 0%	1 2.3%
Severity of Flatulence (participants) [Number]
1- absent	3 13.6%	4 18.2%	7 15.9%
2- light	11 50%	10 45.5%	21 47.7%
3- moderate	8 36.4%	8 36.4%	16 36.4%
4- serious	0 0%	0 0%	0 0%
Frequency of Lack of Appetite (participants) [Number]
1- never	1 4.5%	5 22.7%	6 13.6%
2- rare	10 45.5%	13 59.1%	23 52.3%
3- frequently	8 36.4%	4 18.2%	12 27.3%
4- constantly	3 13.6%	0 0%	3 6.8%
Severity of Lack of Appetite (participants) [Number]
1- absent	1 4.5%	5 22.7%	6 13.6%
2- light	11 50%	13 59.1%	24 54.5%
3- moderate	7 31.8%	4 18.2%	11 25%
4- serious	3 13.6%	0 0%	3 6.8%
Frequency of Bloating (participants) [Number]
1- never	2 9.1%	4 18.2%	6 13.6%
2- rare	7 31.8%	7 31.8%	14 31.8%
3- frequently	12 54.5%	10 45.5%	22 50%
4- constantly	1 4.5%	1 4.5%	2 4.5%
Severity of Bloating (participants) [Number]
1- absent	2 9.1%	4 18.2%	6 13.6%
2- light	7 31.8%	7 31.8%	14 31.8%
3- moderate	13 59.1%	10 45.5%	23 52.3%
4- serious	0 0%	1 4.5%	1 2.3%
Frequency of Nausea (participants) [Number]
1- never	11 50%	15 68.2%	26 59.1%
2- rare	8 36.4%	7 31.8%	15 34.1%
3- frequently	3 13.6%	0 0%	3 6.8%
4- constantly	0 0%	0 0%	0 0%
Severity of Nausea (participants) [Number]
1- absent	11 50%	15 68.2%	26 59.1%
2- light	9 40.9%	6 27.3%	15 34.1%
3- moderate	2 9.1%	1 4.5%	3 6.8%
4- serious	0 0%	0 0%	0 0%
Frequency of Vomiting (participants) [Number]
1- never	16 72.7%	18 81.8%	34 77.3%
2- rare	6 27.3%	4 18.2%	10 22.7%
3- frequently	0 0%	0 0%	0 0%
4- constantly	0 0%	0 0%	0 0%
Severity of Vomiting (participants) [Number]
1- absent	16 72.7%	18 81.8%	34 77.3%
2- light	6 27.3%	4 18.2%	10 22.7%
3- moderate	0 0%	0 0%	0 0%
4- serious	0 0%	0 0%	0 0%
Frequency of Heart Burn (participants) [Number]
1- never	17 77.3%	18 81.8%	35 79.5%
2- rare	1 4.5%	2 9.1%	3 6.8%
3- frequently	4 18.2%	2 9.1%	6 13.6%
4- constantly	0 0%	0 0%	0 0%
Severity of Heart Burn (participants) [Number]
1- absent	17 77.3%	18 81.8%	35 79.5%
2- light	1 4.5%	1 4.5%	2 4.5%
3- moderate	4 18.2%	3 13.6%	7 15.9%
4- serious	0 0%	0 0%	0 0%
Frequency of Diarrhea (participants) [Number]
1- never	9 40.9%	9 40.9%	18 40.9%
2- rare	9 40.9%	11 50%	20 45.5%
3- frequently	4 18.2%	2 9.1%	6 13.6%
4- constantly	0 0%	0 0%	0 0%
Severity of Diarrhea (participants) [Number]
1- absent	9 40.9%	10 45.5%	19 43.2%
2- light	10 45.5%	10 45.5%	20 45.5%
3- moderate	3 13.6%	2 9.1%	5 11.4%
4- serious	0 0%	0 0%	0 0%
Frequency of More than 2 Bowel Movements Per Day (participants) [Number]
1- never	4 18.2%	10 45.5%	14 31.8%
2- rare	12 54.5%	6 27.3%	18 40.9%
3- frequently	5 22.7%	6 27.3%	11 25%
4- constantly	1 4.5%	0 0%	1 2.3%
Severity of More Than 2 Bowel Movements Per Day (participants) [Number]
1- absent	4 18.2%	10 45.5%	14 31.8%
2- light	12 54.5%	8 36.4%	20 45.5%
3- moderate	5 22.7%	4 18.2%	9 20.5%
4- serious	1 4.5%	0 0%	1 2.3%
Frequency of Less Than 2 Bowel Movements Per Week (participants) [Number]
1- never	18 81.8%	17 77.3%	35 79.5%
2- rare	0 0%	2 9.1%	2 4.5%
3- frequently	4 18.2%	3 13.6%	7 15.9%
4- constantly	0 0%	0 0%	0 0%
Severity of Less Than 2 Bowel Movements Per Week (participants) [Number]
1- absent	18 81.8%	17 77.3%	35 79.5%
2- light	0 0%	3 13.6%	3 6.8%
3- moderate	4 18.2%	2 9.1%	6 13.6%
4- serious	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Weight Percentile at 3 Months
Description	Weight Percentile at 3 months adjusted for sex and age
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

All participants.

Arm/Group Title	Oral Reduced L-glutathione	Placebo Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. Oral reduced l-glutathione: The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
Mean (Standard Deviation) [Weight Percentile, sex and age adjusted]	33.5 (14.9)	31.0 (13.4)

2. Primary Outcome

Title	Height Percentile
Description	Height Percentile adjusted for sex and age
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

All participants.

Arm/Group Title	Oral Reduced L-glutathione	Placebo Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. Oral reduced l-glutathione: The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
Mean (Standard Deviation) [Percentile adjusted for age and sex]	39.3 (11.9)	38.0 (13.8)

3. Primary Outcome

Title	BMI Percentile
Description	Body Mass Index percentile adjusted for sex and age. Standard BMI are not available for participants under 2 years of age
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

BMI percentile not available for children under 2 years of age.

Arm/Group Title	Oral Reduced L-glutathione	Placebo Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. Oral reduced l-glutathione: The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	20	20
Mean (Standard Deviation) [Percentile adjusted for age and sex]	37.1 (33.6)	47.5 (17.0)

4. Secondary Outcome

Title	Forced Vital Capacity
Description	Forced vital capacity percent predicted
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Pulmonary function tests not performed on children under the age of 5

Arm/Group Title	Oral Reduced L-glutathione	Placebo Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. Oral reduced l-glutathione: The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	11	9
Mean (Standard Deviation) [percent predicted]	87.2 (7.2)	88.8 (10.3)

5. Secondary Outcome

Title	FEV1
Description	Forced expiratory volume at one second, percent predicted
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Pulmonary function tests not performed on children under the age of 5

Arm/Group Title	Oral Reduced L-glutathione	Placebo Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. Oral reduced l-glutathione: The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	11	9
Mean (Standard Deviation) [Percent predicted]	73.2 (5.6)	73.0 (11.1)

6. Secondary Outcome

Title	Bacteriology
Description	Expectorated sputum or throat swab
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Reduced L-glutathione	Placebo Oral Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
A. xylososidans	1 4.5%	0 0%
MRSA	0 0%	0 0%
PA	0 0%	4 18.2%
Staph	12 54.5%	9 40.9%
Normal flora	4 18.2%	2 9.1%
PA and S. maltophilia	0 0%	0 0%
PA and Staph	4 18.2%	7 31.8%
Staph and A. xylososidans	0 0%	0 0%
S. maltophilia	1 4.5%	0 0%

7. Secondary Outcome

Title	Forced Vital Capacity
Description	Percent predicted of forced vital capacity.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

PFT's not done on children under age of 5.

Arm/Group Title	Oral Reduced L-glutathione	Placebo Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. Oral reduced l-glutathione: The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	11	9
Mean (Standard Deviation) [Percent Predicted]	92.3 (7.3)	83.9 (8.2)

8. Secondary Outcome

Title	FEV1
Description	Forced expiratory volume at one second, percent predicted.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

PFT's not done on children under age of 5.

Arm/Group Title	Oral Reduced L-glutathione	Placebo Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. Oral reduced l-glutathione: The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	11	9
Mean (Standard Deviation) [Percent predicted]	81.5 (4.9)	71.6 (8.3)

9. Secondary Outcome

Title	C-Reactive Protein (CRP)
Description	CRP was measured to determine if this test fell during the course of treatment.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

All participants.

Arm/Group Title	Oral Reduced L-glutathione	Placebo Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. Oral reduced l-glutathione: The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
Mean (Standard Deviation) [milligrams per liter]	10.9 (5.6)	14.7 (6.5)

10. Primary Outcome

Title	BMI Percentile
Description	Body Mass Index percentile adjusted for sex and age. Not available for participants under 2 years of age.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

All old enough to have BMI percentile calculated. BMI percentile not available for children under 2 years of age

Arm/Group Title	Oral Reduced L-glutathione	Placebo Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. Oral reduced l-glutathione: The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	20	20
Mean (Standard Deviation) [Percentile adjusted for age and sex]	47.5 (14.0)	36.0 (17.0)

11. Secondary Outcome

Title	White Blood Cell Count
Description	White blood cell count was measure at the beginning and end of the study to determine if treatment affected this test.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

All participants.

Arm/Group Title	Oral Reduced L-glutathione	Placebo Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. Oral reduced l-glutathione: The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
Mean (Standard Deviation) [1000 cells/mm^3]	8.4 (1.5)	9.5 (2.4)

12. Secondary Outcome

Title	Vitamin E
Description	Serum Vitamin E levels were measured to determine if treatment affected this test.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

All participants.

Arm/Group Title	Oral Reduced L-glutathione	Placebo Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. Oral reduced l-glutathione: The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
Mean (Standard Deviation) [milligrams per liter]	8.6 (1.6)	6.8 (1.4)

13. Primary Outcome

Title	Weight Percentile
Description	Weight percentile, adjusted for sex and age
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

All participants.

Arm/Group Title	Oral Reduced L-glutathione	Placebo Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. Oral reduced l-glutathione: The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
Mean (Standard Deviation) [Percentile adjusted for age and sex]	43.2 (12.3)	31.8 (14.0)

14. Primary Outcome

Title	Height Percentile
Description	The subjects were measured over the course of the study to determine if treatment improved height percentile.
Time Frame	6 Months

Outcome Measure Data

Analysis Population Description

All participants.

Arm/Group Title	Oral Reduced L-glutathione	Placebo Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. Oral reduced l-glutathione: The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
Mean (Standard Deviation) [Percentile adjusted for age and sex]	43.3 (12.5)	36.5 (13.2)

15. Primary Outcome

Title	Fecal Calprotectin
Description	Fecal Calprotectin, a measure of gut inflammation, was measured to see if the treatment decreased this outcome.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

All participants.

Arm/Group Title	Oral Reduced L-glutathione	Placebo Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. Oral reduced l-glutathione: The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
Mean (Standard Deviation) [Micrograms/gram feces]	61.2 (26.4)	76.6 (30.7)

16. Secondary Outcome

Title	Alanine Aminotransferase (ALT)
Description	ALT was measured to determine if liver function was affected by treatment over the course of the study.
Time Frame	6 Months

Outcome Measure Data

Analysis Population Description

All participants.

Arm/Group Title	Oral Reduced L-glutathione	Placebo Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. Oral reduced l-glutathione: The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
Mean (Standard Deviation) [units per liter]	18.1 (7.0)	25.8 (10.9)

17. Secondary Outcome

Title	Bacteriology
Description	Expectorated sputum or throat swab
Time Frame	6 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Reduced L-glutathione	Placebo Oral Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
A. xylososidans	0 0%	0 0%
MRSA	0 0%	1 4.5%
PA	1 4.5%	7 31.8%
Staph	12 54.5%	8 36.4%
Noraml flora	6 27.3%	0 0%
PA and S. maltophilia	0 0%	0 0%
PA and Staph	1 4.5%	5 22.7%
Staph and A. xylososidans	0 0%	0 0%
S. maltophilia	1 4.5%	1 4.5%
Strep B	1 4.5%	0 0%

18. Secondary Outcome

Title	Frequency of Abdominal Pain
Description	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Reduced L-glutathione	Placebo Oral Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
1- never	15 68.2%	9 40.9%
2- rare	6 27.3%	7 31.8%
3- frequently	1 4.5%	6 27.3%
4- constantly	0 0%	0 0%
Did Not Answer	0 0%	0 0%

19. Secondary Outcome

Title	Severity of Abdominal Pain
Description	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Reduced L-glutathione	Placebo Oral Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
1- absent	14 63.6%	9 40.9%
2- light	7 31.8%	9 40.9%
3- moderate	0 0%	3 13.6%
4- serious	0 0%	0 0%
Did Not Answer	1 4.5%	1 4.5%

20. Secondary Outcome

Title	Frequency of Belching
Description	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Reduced L-glutathione	Placebo Oral Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
1- never	18 81.8%	11 50%
2- rare	4 18.2%	6 27.3%
3- frequently	0 0%	5 22.7%
4- constantly	0 0%	0 0%
Did Not Answer	0 0%	0 0%

21. Secondary Outcome

Title	Severity of Belching
Description	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Reduced L-glutathione	Placebo Oral Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
1- absent	18 81.8%	11 50%
2- light	3 13.6%	6 27.3%
3- moderate	0 0%	4 18.2%
4- serious	0 0%	0 0%
Did Not Answer	1 4.5%	1 4.5%

22. Secondary Outcome

Title	Frequency of Flatulence
Description	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Reduced L-glutathione	Placebo Oral Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
1- never	7 31.8%	3 13.6%
2- rare	14 63.6%	10 45.5%
3- frequently	1 4.5%	9 40.9%
4- constantly	0 0%	0 0%
Did Not Answer	0 0%	0 0%

23. Secondary Outcome

Title	Severity of Flatulence
Description	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Reduced L-glutathione	Placebo Oral Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
1- absent	7 31.8%	3 13.6%
2- light	13 59.1%	11 50%
3- moderate	1 4.5%	7 31.8%
4- serious	0 0%	0 0%
Did Not Answer	1 4.5%	1 4.5%

24. Secondary Outcome

Title	Frequency of Lack of Appetite
Description	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Reduced L-glutathione	Placebo Oral Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
1- never	11 50%	4 18.2%
2- rare	11 50%	14 63.6%
3- frequently	0 0%	4 18.2%
4- constantly	0 0%	0 0%
Did Not Answer	0 0%	0 0%

25. Secondary Outcome

Title	Severity of Lack of Appetite
Description	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Reduced L-glutathione	Placebo Oral Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
1- absent	11 50%	3 13.6%
2- light	10 45.5%	14 63.6%
3- moderate	0 0%	4 18.2%
4- serious	0 0%	0 0%
Did Not Answer	1 4.5%	1 4.5%

26. Secondary Outcome

Title	Frequency of Bloating
Description	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Reduced L-glutathione	Placebo Oral Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
1- never	6 27.3%	2 9.1%
2- rare	14 63.6%	9 40.9%
3- frequently	2 9.1%	10 45.5%
4- constantly	0 0%	1 4.5%
Did Not Answer	0 0%	0 0%

27. Secondary Outcome

Title	Severity of Bloating
Description	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Reduced L-glutathione	Placebo Oral Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
1- absent	6 27.3%	2 9.1%
2- light	14 63.6%	11 50%
3- moderate	1 4.5%	7 31.8%
4- serious	0 0%	1 4.5%
Did Not Answer	1 4.5%	1 4.5%

28. Secondary Outcome

Title	Frequency of Nausea
Description	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Reduced L-glutathione	Placebo Oral Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
1- never	14 63.6%	14 63.6%
2- rare	8 36.4%	7 31.8%
3- frequently	0 0%	1 4.5%
4- constantly	0 0%	0 0%
Did Not Answer	0 0%	0 0%

29. Secondary Outcome

Title	Severity of Nausea
Description	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Reduced L-glutathione	Placebo Oral Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
1- absent	13 59.1%	13 59.1%
2- light	8 36.4%	7 31.8%
3- moderate	0 0%	1 4.5%
4- serious	0 0%	0 0%
Did Not Answer	1 4.5%	1 4.5%

30. Secondary Outcome

Title	Frequency of Vomiting
Description	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Reduced L-glutathione	Placebo Oral Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
1- never	21 95.5%	15 68.2%
2- rare	1 4.5%	7 31.8%
3- frequently	0 0%	0 0%
4- constantly	0 0%	0 0%
Did Not Answer	0 0%	0 0%

31. Secondary Outcome

Title	Severity of Vomiting
Description	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Reduced L-glutathione	Placebo Oral Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
1- absent	20 90.9%	14 63.6%
2- light	1 4.5%	7 31.8%
3- moderate	0 0%	0 0%
4- serious	0 0%	0 0%
Did Not Answer	1 4.5%	1 4.5%

32. Secondary Outcome

Title	Frequency of Heart Burn
Description	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Reduced L-glutathione	Placebo Oral Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
1- never	17 77.3%	18 81.8%
2- rare	5 22.7%	3 13.6%
3- frequently	0 0%	1 4.5%
4- constantly	0 0%	0 0%
Did Not Answer	0 0%	0 0%

33. Secondary Outcome

Title	Severity of Heart Burn
Description	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Reduced L-glutathione	Placebo Oral Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
1- absent	17 77.3%	18 81.8%
2- light	4 18.2%	2 9.1%
3- moderate	0 0%	1 4.5%
4- serious	0 0%	0 0%
Did Not Answer	1 4.5%	1 4.5%

34. Secondary Outcome

Title	Frequency of Diarrhea
Description	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Reduced L-glutathione	Placebo Oral Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
1- never	18 81.8%	11 50%
2- rare	4 18.2%	8 36.4%
3- frequently	0 0%	3 13.6%
4- constantly	0 0%	0 0%
Did Not Answer	0 0%	0 0%

35. Secondary Outcome

Title	Severity of Diarrhea
Description	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Reduced L-glutathione	Placebo Oral Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
1- absent	17 77.3%	10 45.5%
2- light	4 18.2%	8 36.4%
3- moderate	0 0%	3 13.6%
4- serious	0 0%	0 0%
Did Not Answer	1 4.5%	1 4.5%

36. Secondary Outcome

Title	Frequency of More Than 2 Bowel Movements Per Day
Description	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Reduced L-glutathione	Placebo Oral Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
1- never	15 68.2%	12 54.5%
2- rare	6 27.3%	3 13.6%
3- frequently	1 4.5%	7 31.8%
4- constantly	0 0%	0 0%
Did Not Answer	0 0%	0 0%

37. Secondary Outcome

Title	Severity of More Than 2 Bowel Movements Per Day
Description	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Reduced L-glutathione	Placebo Oral Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
1- absent	14 63.6%	12 54.5%
2- light	7 31.8%	4 18.2%
3- moderate	0 0%	5 22.7%
4- serious	0 0%	0 0%
Did Not Answer	1 4.5%	1 4.5%

38. Secondary Outcome

Title	Frequency of Less Than 2 Bowel Movements Per Week
Description	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most frequent
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Reduced L-glutathione	Placebo Oral Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
1- never	19 86.4%	16 72.7%
2- rare	3 13.6%	5 22.7%
3- frequently	0 0%	1 4.5%
4- constantly	0 0%	0 0%
Did Not Answer	0 0%	0 0%

39. Secondary Outcome

Title	Severity of Less Than 2 Bowel Movements Per Week
Description	Part of the Qualitative Symptom Assessment; scaled from 1-4 with 4 being the most severe
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oral Reduced L-glutathione	Placebo Oral Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.	The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
Measure Participants	22	22
1- absent	17 77.3%	15 68.2%
2- light	4 18.2%	4 18.2%
3- moderate	0 0%	2 9.1%
4- serious	0 0%	0 0%
Did Not Answer	1 4.5%	1 4.5%

Adverse Events

Time Frame	6 months of the trial
Adverse Event Reporting Description	Patients kept a daily journal. They reported change in symptoms such as bloating, abdominal pain, as well as anorexia and hunger.
Arm/Group Title	Oral Reduced L-glutathione		Placebo Calcium Citrate
Arm/Group Description	The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. Oral reduced l-glutathione: The treatment was pharmaceutical-grade Reduced L-Glutathione (GSH) with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.		The placebo was calcium citrate with a daily dose of 65 mg/kg. The daily dose of each substance was divided into three doses given at mealtime.
All Cause Mortality
	Oral Reduced L-glutathione		Placebo Calcium Citrate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Oral Reduced L-glutathione		Placebo Calcium Citrate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/22 (0%)
Other (Not Including Serious) Adverse Events
	Oral Reduced L-glutathione		Placebo Calcium Citrate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/22 (0%)

Limitations/Caveats

This trial was limited to one site. The number was relatively small. Since PFT's were not done on children under the age of 5, there is even smaller number of participants contributing PFT data.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.