Impact of KUVAN® on Gastric Relaxation in Women With Diabetic Gastroparesis.

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01135186
• Collaborator: (none)
• Enrollment: 9
• Location: 1
• Arm: 1
• Duration (Months): 30.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Kuvan® (sapropterin dihydrochloride) for Improving Gastric Accommodation in Women with Diabetic Gastroparesis (KIGA-DG)

Condition or Disease	Intervention/Treatment	Phase
Gastroparesis	Drug: sapropterin dihydrochloride	N/A

Detailed Description

Patients are invited to participate in a research study of Kuvan® (sapropterin dihydrochloride). We hope to learn whether treatment with Kuvan® is safe and effective in improving the ability of the stomach to relax after eating and improving the symptoms of diabetic gastroparesis. Women are selected as a possible participant in this study because they have diabetes and moderate to severe gastroparesis (meaning stomach empties slowly).

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Kuvan® (Sapropterin Dihydrochloride) for Improving Gastric Accommodation in Women With Diabetic Gastroparesis (KIGA-DG)
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Nov 1, 2012
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Other: Sapropterin open label study of sapropterin dihydrochloride	Drug: sapropterin dihydrochloride; sapropterin dihydrochloride: 10mg/kg/day; Other Names: KUVAN

Outcome Measures

Primary Outcome Measures

1. Gastric Accommodation [Baseline, 4 Weeks, 8 Weeks]

   Gastric Accommodation refers to the reflexive relaxation of the upper stomach after swallowing as measured by the Satiety Test at baseline, 4 weeks, and 8 weeks. Increased gastric accommodation is considered a positive outcome.

Secondary Outcome Measures

1. Secondary Outcome Measures Will Include Change in Symptom Severity. [Baseline, 4 Weeks, 8 Weeks]

   Change in symptom severity over the past 2 weeks as measured by the patient reported Gastroparesis Cardinal Symptom Index (GCSI) The GCSI is composed of 9 questions. Each question asks about symptom severity on a scale of 1-5 listed below. 0=None 1= Very mild 2= Mild 3=Moderate 4=Severe 5= Very severe The 9 scores are summed together for cumulative GCSI score. The minimum cumulative score is '"0" and the maximum cumulative score is "45." Once we calculated the cumulative score for each participant, we took the average of all participants cumulative scores giving us the sample mean. This was done at baseline, week 4, and week 8. Higher total scores indicate higher symptom severity. Lower total scores indicate lower symptom severity.

2. Secondary Outcome Measures Will Include Change in Quality of Life. [Baseline, 4 Weeks, 8 Weeks]

   Quality of life as impacted by patients with upper gastrointestinal disorders (PAGI-QOL) The PAGI-QOl is composed of 30 questions. Each question asks about the degree to which a patient's quality of life is impacted by upper gastrointestinal disorders. Questions measure quality of life impact on a scale of 1-5 listed below. 0=none of the time, 1=a little of the time, 2=some of the time, 3=a good bit of the time, 4= most of the time, 5= all of time The 30 items are summed together for a cumulative PAGI-QOL score. The minimum cumulative score is "0" and the maximum score is "150." Once we calculated the cumulative score for each participant, we took the average of all participants cumulative scores giving us the sample mean. This was done at baseline, week 4, and week 8. Lower scores indicate an improved overall quality of life. Higher scores indicate a diminished overall quality of life.

3. Secondary Outcome Measures Will Include Change in Symptom Severity as Measured by the Patient Assessment of Gastrointestinal Disorder-Symptom Severity Index Disorders Symptom Severity Index (PAGI-SYM) [Baseline, 4 Weeks, 8 Weeks]

   Symptom severity as measured by the Patient Assessment of Upper Gastrointestinal Disorder- Symptom Severity Index. (PAGI-SYM) The PAGI-SYM is compose of 20 questions. Each question can be answered on a scale of 1-5 (below) 0 = none, 1=very mild, 2=mild, 3=moderate, 4=severe, 5=very severe Cumulative scores were calculated by summing all 20 questions. The minimum cumulative scores would be "0" while the maximum cumulative score would be "100" Once we calculated the cumulative score for each participant, we took the average of all the cumulative scores giving us the sample mean. This was done at baseline, week 4, and week 8. Lower score indicates decreased symptom severity. Higher score indicates increased symptom severity.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:Inclusion Criteria

Patients with moderate to severe symptoms of diabetic gastroparesis will be studied (GCSI

21). Patients should not have post-surgical gastroparesis or dyspeptic symptoms with normal gastric emptying. In order to qualify for inclusion in the trial, patients must satisfy the following inclusion criteria:

1. Diagnosis of diabetes mellitus > 5 years requiring medical therapy

2. Female gender

3. Ages 18-65 years

4. Documentation of delayed gastric emptying on gastric emptying scintigraphy (within 2 years of enrollment)

5. Symptoms of gastroparesis for at least 6 months with Gastroparesis Cardinal Symptom Index (GCSI) score > 21 indicating moderate to severe symptoms

6. Recent negative upper endoscopy or upper GI series within 2 years of enrollment (no evidence of mechanical obstruction or peptic ulcer disease)

Exclusion Criteria:Exclusion Criteria

Patients who satisfy any of the following exclusion criteria will be ineligible for enrollment in the study:

1. Diabetes diagnosed < 5 years prior to the study

2. Male gender

3. Normal gastric emptying

4. Gastroparesis from post-surgical etiologies

5. Another active disorder, which could explain symptoms in the opinion of the investigator

6. Pregnancy

7. History of significant cardiac arrhythmias and/or prolonged QTc

8. Daily use of narcotic analgesics for abdominal pain

9. Contraindications to gastric emptying breath test: patients with a known allergy to egg, wheat, or algae.

10. Underlying seizure disorder

11. Known history of cardiac ischemia

12. Recent clinically significant gastrointestinal bleeding

13. Patients taking Levodopa

14. Any other condition, which in the opinion of the investigator would impede compliance or hinder the completion of the study

15. Failure to give informed consent

16. Surgery for placement of a gastric stimulator within the past 6 months (patients > 6 months post-op with persistent symptoms and delayed gastric emptying are eligible).

17. A normal upper endoscopy not performed within 2 year of study entry.

18. Patients taking phosphodiesterase inhibitors such as sildenafil, vardenafil, tadalafil

19. Patients with renal impairment (i.e. Creatinine > 2.5 mg/dL)

20. Patients with hepatic dysfunction (i.e. ALT and AST values > 2.5x ULN and T. bilirubin

1.5x ULN)

1. Patients with uncontrolled diabetes, such as HbA1c > 10 mg/dl at screening/baseline will be excluded.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Linda A Nguyen, Stanford University
• Principal Investigator: Pankaj Jay Pasricha, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

• Bell RA, Jones-Vessey K, Summerson JH. Hospitalizations and outcomes for diabetic gastroparesis in North Carolina. South Med J. 2002 Nov;95(11):1297-9.
• Gangula PR, Maner WL, Micci MA, Garfield RE, Pasricha PJ. Diabetes induces sex-dependent changes in neuronal nitric oxide synthase dimerization and function in the rat gastric antrum. Am J Physiol Gastrointest Liver Physiol. 2007 Mar;292(3):G725-33.
• Smirnova VI, Gridchik IE, Tregubenko AD, Khachaturova EA. [Analgesia and intensive therapy during hemicorporectomy]. Anesteziol Reanimatol. 1991 Sep-Oct;(5):46-8. Russian.
• Soykan I, Sivri B, Sarosiek I, Kiernan B, McCallum RW. Demography, clinical characteristics, psychological and abuse profiles, treatment, and long-term follow-up of patients with gastroparesis. Dig Dis Sci. 1998 Nov;43(11):2398-404.
• Stacher G. Diabetes mellitus and the stomach. Diabetologia. 2001 Sep;44(9):1080-93. Review. Erratum in: Diabetologia 2002 Feb;45(2):293.
• Werner ER, Gorren AC, Heller R, Werner-Felmayer G, Mayer B. Tetrahydrobiopterin and nitric oxide: mechanistic and pharmacological aspects. Exp Biol Med (Maywood). 2003 Dec;228(11):1291-302. Review.

• Responsible Party: Linda Nguyen, Principle Investigator, Stanford University
• ClinicalTrials.gov Identifier: NCT01135186
• Other Study ID Numbers: SU-03252010-5462
• First Posted: Jun 2, 2010
• Last Update Posted: Sep 10, 2019
• Last Verified: Sep 1, 2019

• Additional relevant MeSH terms: Gastroparesis; Verapamil

Study Results

Participant Flow

Recruitment Details	9 women with moderate to severe gastroparesis were enrolled at medical clinic.

Arm/Group Title	Open Label Study
Arm/Group Description	sapropterin dihydrochloride sapropterin dihydrochloride: sapropterin dihydrochloride: 10mg/kg/day
Period Title: Overall Study
STARTED	9
COMPLETED	9
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Open Label Study
Arm/Group Description	sapropterin dihydrochloride sapropterin dihydrochloride: sapropterin dihydrochloride: 10mg/kg/day (week 1 through week 4) sapropterin dihydrochloride: sapropterin dihydrochloride: 20mg/kg/day (week 5 through week 8)
Overall Participants	9
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	9 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.56 (15.03)
Sex: Female, Male (Count of Participants)
Female	9 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	9 100%

Outcome Measures

1. Primary Outcome

Title	Gastric Accommodation
Description	Gastric Accommodation refers to the reflexive relaxation of the upper stomach after swallowing as measured by the Satiety Test at baseline, 4 weeks, and 8 weeks. Increased gastric accommodation is considered a positive outcome.
Time Frame	Baseline, 4 Weeks, 8 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Open Label Study
Arm/Group Description	sapropterin dihydrochloride sapropterin dihydrochloride: sapropterin dihydrochloride: 10mg/kg/day
Measure Participants	9
Baseline	322.22 (137.18)
4 Weeks	402.78 (197.03)
8 Weeks	450.63 (301.50)

2. Secondary Outcome

Title	Secondary Outcome Measures Will Include Change in Symptom Severity.
Description	Change in symptom severity over the past 2 weeks as measured by the patient reported Gastroparesis Cardinal Symptom Index (GCSI) The GCSI is composed of 9 questions. Each question asks about symptom severity on a scale of 1-5 listed below. 0=None 1= Very mild 2= Mild 3=Moderate 4=Severe 5= Very severe The 9 scores are summed together for cumulative GCSI score. The minimum cumulative score is '"0" and the maximum cumulative score is "45." Once we calculated the cumulative score for each participant, we took the average of all participants cumulative scores giving us the sample mean. This was done at baseline, week 4, and week 8. Higher total scores indicate higher symptom severity. Lower total scores indicate lower symptom severity.
Time Frame	Baseline, 4 Weeks, 8 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Open Label Study
Arm/Group Description	sapropterin dihydrochloride sapropterin dihydrochloride: sapropterin dihydrochloride: 10mg/kg/day week 1-4, 20mg/kg/day week 5-8.
Measure Participants	9
Baseline	32.00 (8.67)
4 Weeks	23.25 (13.91)
8 Weeks	23.67 (13.91)

3. Secondary Outcome

Title	Secondary Outcome Measures Will Include Change in Quality of Life.
Description	Quality of life as impacted by patients with upper gastrointestinal disorders (PAGI-QOL) The PAGI-QOl is composed of 30 questions. Each question asks about the degree to which a patient's quality of life is impacted by upper gastrointestinal disorders. Questions measure quality of life impact on a scale of 1-5 listed below. 0=none of the time, 1=a little of the time, 2=some of the time, 3=a good bit of the time, 4= most of the time, 5= all of time The 30 items are summed together for a cumulative PAGI-QOL score. The minimum cumulative score is "0" and the maximum score is "150." Once we calculated the cumulative score for each participant, we took the average of all participants cumulative scores giving us the sample mean. This was done at baseline, week 4, and week 8. Lower scores indicate an improved overall quality of life. Higher scores indicate a diminished overall quality of life.
Time Frame	Baseline, 4 Weeks, 8 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Open Label Study
Arm/Group Description	sapropterin dihydrochloride sapropterin dihydrochloride: sapropterin dihydrochloride: 10mg/kg/day weeks (1-4) and 20mg/kg/days weeks (week 5-8)
Measure Participants	9
Baseline	91.22 (28.27)
4 Weeks	61.29 (37.83)
8 Weeks	60.50 (40.90)

4. Secondary Outcome

Title	Secondary Outcome Measures Will Include Change in Symptom Severity as Measured by the Patient Assessment of Gastrointestinal Disorder-Symptom Severity Index Disorders Symptom Severity Index (PAGI-SYM)
Description	Symptom severity as measured by the Patient Assessment of Upper Gastrointestinal Disorder- Symptom Severity Index. (PAGI-SYM) The PAGI-SYM is compose of 20 questions. Each question can be answered on a scale of 1-5 (below) 0 = none, 1=very mild, 2=mild, 3=moderate, 4=severe, 5=very severe Cumulative scores were calculated by summing all 20 questions. The minimum cumulative scores would be "0" while the maximum cumulative score would be "100" Once we calculated the cumulative score for each participant, we took the average of all the cumulative scores giving us the sample mean. This was done at baseline, week 4, and week 8. Lower score indicates decreased symptom severity. Higher score indicates increased symptom severity.
Time Frame	Baseline, 4 Weeks, 8 Weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Open Label Study
Arm/Group Description	sapropterin dihydrochloride sapropterin dihydrochloride: sapropterin dihydrochloride: 10mg/kg/day week 1-4, 20mg/kg/day week 5-8.
Measure Participants	9
Baseline	54.89 (17.14)
4 Weeks	41.50 (23.08)
8 Weeks	34.50 (19.71)

Adverse Events

Arm/Group Title	Open Label Study
Arm/Group Description	sapropterin dihydrochloride sapropterin dihydrochloride: sapropterin dihydrochloride: 10mg/kg/day (week 1-4) 20 mg/kg/day (week 5-8)
All Cause Mortality
	Open Label Study
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Open Label Study
	Affected / at Risk (%)	# Events
Total	1/9 (11.1%)
Gastrointestinal disorders
Hospitalization for gastroparesis flareup	1/9 (11.1%)	1
Other (Not Including Serious) Adverse Events
	Open Label Study
	Affected / at Risk (%)	# Events
Total	0/9 (0%)

Limitations/Caveats

A larger sample size is required to confirm the efficacy of saproptetin in increasing gastric accommodation and decreasing gastroparesis symptoms. This would assist in optimal dosing and duration of therapy.

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.