Safety of VSL#3 in Adult Asthmatics

• Sponsor: University of Maryland, Baltimore (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00852124
• Collaborator: National Center for Complementary and Integrative Health (NCCIH) (NIH)
• Enrollment: 3
• Location: 1
• Arms: 2
• Duration (Months): 71
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

We are proposing to test the safety of the probiotic, VSL#3, in a placebo controlled double blind safety study in 30 asthmatic adults. This adult safety trial was requested by the FDA IND review of a pediatric asthma protocol.

Adults with a doctor diagnosis of persistent asthma will take VSL#3 or placebo twice daily for 3 months. Data will be collected, including age, race, height, and weight, present medications, past medical history with emphasis on signs/symptoms of asthma.

On visits to the clinic we will evaluate

• Changes in lung function

• Intestinal permeability

• Intestinal bacteria

• Levels of inflammation in the blood

• Women will have repeat urine pregnancy testing at each clinic visit

Condition or Disease	Intervention/Treatment	Phase
Asthma	Biological: VSL#3; Biological: VSL#3 or placebo	Phase 1/Phase 2

Detailed Description

The monitored parameters that will be assessed at each clinic visit or phone call include:

1. the number of days with asthma related symptoms of cough, wheeze, dyspnea, awakening at night, and exercise limitation.

2. the number of asthma-related missed school/work days

3. the amount of use of asthma rescue medications

4. use of non-inhaled steroids

5. change in medications from baseline visit

6. diarrhea/liquid stools (> 2/day)

7. constipation

8. gas/bloating

9. fever/chills

10. scheduled or unscheduled visits for health care

To monitor for increased risk of safety concerns, we will also inquire on follow up visits and phone calls about the following:

1. household member with immunosuppression such as HIV or chemotherapy.

On visits to the clinic we will evaluate lung function by spirometry:

1. change in lung function with spirometry.

2. women of childbearing potential will have repeat urine pregnancy testing at each clinic visit.

3. intestinal barrier function

4. intestinal flora

5. serum inflammatory cytokines and IgE

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Safety of VSL#3 for Adult Asthmatics
• Study Start Date: Feb 1, 2007
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Jan 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Packets similar to VSL#3 will be taken 2 X daily but not containing active bacteria	Biological: VSL#3 or placebo; 1 packet 2 x daily of placebo
Active Comparator: VSL#3 Packets of VSL#3 (powder containing 8 bacteria believed to be beneficial) will be taken 2 x daily in food or a cool beverage.	Biological: VSL#3; VSL#3 2 times daily

Outcome Measures

Primary Outcome Measures

1. Safety of VSL#3 in Adults Asthmatics [3 months]

   Change in FEV in adult asthmatics receiving VSL3# as compared to controls receiving placebo.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Adults age 18-64 years old.

2. Doctor diagnosis of mild persistent asthma. Persistent asthma is defined by NAEPP guidelines as asthma symptoms (cough/wheeze/dyspnea/exercise limitation)of greater than 2 times/week daytime or greater than 2 times/month at night over the previous month but less than continual and less than 5 nights/week.

3. FEV1 greater than 60% predicted for age/gender/race/height based on normative data.

4. No unscheduled asthma related health visit in the 1 month prior to enrollment

5. School or work days missed less than or equal to 2 in the previous month for asthma.

6. Albuterol use less than 8 doses (2 puffs or one neb) in past week.

7. Ability to speak and understand English.

8. Telephone access.

9. Women of childbearing potential must confirm that they will use birth control while in the study and have a negative urine pregnancy screen at baseline.

Exclusion Criteria:

1. Pregnant women, prisoners.

2. Chronic illness (other than asthma, allergic rhinitis and eczema) such as renal disease, diabetes, hypertension or terminal disease or abnormal vital signs: T> 100.3F, HR>130 bpm, SBP>155 mmHg, or DBP>100 mmHg, RR>25 bpm, or pox<93% room air.

3. Unable to perform spirometry, necessary for lung function assessment.

4. Received probiotic in past 6 months.

5. Subject or household member has immunosuppression such as HIV, history of organ transplantation, present cancer or chemotherapy, primary immune disease, or is taking an immune modulating drug.

6. Severe persistent asthmatics who have continual daily or frequent (greater than 5 nights/week) asthma symptoms and/or FEV1 less than 60% predicted .

7. Diarrhea or constipation (symptoms more than once in the past week)

8. Unable to feed orally or to consume cornstarch

9. Lung disease other than asthma (e.g. COPD, cystic fibrosis, lung cancer, bronchiectasis, interstitial lung disease).

10. Subjects at increased risk of developing infective endocarditis such as those with a history of cardiac surgery, IV drug abuse, recent invasive medical procedures or dental work (recent = last month).

11. Allergy to Vancomycin or Cefepime. The parameters of intestinal barrier function, intestinal flora, serum inflammatory cytokines, IgE, will have no exclusion ranges as these will be collected over time on product as a way of describing the population characteristics of study participants.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Maryland Baltimore	Baltimore	Maryland	United States	21201

Sponsors and Collaborators

• University of Maryland, Baltimore
• National Center for Complementary and Integrative Health (NCCIH)

Investigators

• Principal Investigator: Alessio Fasano, M. D., MBRC

Study Documents (Full-Text)

None provided.

More Information

Publications

• Bienenstock J, Wiley RE, Neigh GS, Waserman S, Keith P. Probiotics in the management and prevention of atopy. Clin Rev Allergy Immunol. 2002 Jun;22(3):275-85. Review.
• Björkstén B, Naaber P, Sepp E, Mikelsaar M. The intestinal microflora in allergic Estonian and Swedish 2-year-old children. Clin Exp Allergy. 1999 Mar;29(3):342-6. Erratum in: Clin Exp Allergy 2000 Jul;30(7):1047.
• Cannon JP, Lee TA, Bolanos JT, Danziger LH. Pathogenic relevance of Lactobacillus: a retrospective review of over 200 cases. Eur J Clin Microbiol Infect Dis. 2005 Jan;24(1):31-40. Review.
• Hijazi N, Abalkhail B, Seaton A. Diet and childhood asthma in a society in transition: a study in urban and rural Saudi Arabia. Thorax. 2000 Sep;55(9):775-9.
• Hijazi Z, Molla AM, Al-Habashi H, Muawad WM, Molla AM, Sharma PN. Intestinal permeability is increased in bronchial asthma. Arch Dis Child. 2004 Mar;89(3):227-9.
• Isolauri E, Salminen S; Nutrition, Allergy, Mucosal Immunology, and Intestinal Microbiota (NAMI) Research Group Report. Probiotics: use in allergic disorders: a Nutrition, Allergy, Mucosal Immunology, and Intestinal Microbiota (NAMI) Research Group Report. J Clin Gastroenterol. 2008 Jul;42 Suppl 2:S91-6. doi: 10.1097/MCG.0b013e3181639a98. Review.
• Isolauri E, Sütas Y, Kankaanpää P, Arvilommi H, Salminen S. Probiotics: effects on immunity. Am J Clin Nutr. 2001 Feb;73(2 Suppl):444S-450S. doi: 10.1093/ajcn/73.2.444s. Review.
• Kalliomäki M, Isolauri E. Role of intestinal flora in the development of allergy. Curr Opin Allergy Clin Immunol. 2003 Feb;3(1):15-20. Review.
• Kalliomäki M, Salminen S, Arvilommi H, Kero P, Koskinen P, Isolauri E. Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet. 2001 Apr 7;357(9262):1076-9.
• Kalliomäki M, Salminen S, Poussa T, Isolauri E. Probiotics during the first 7 years of life: a cumulative risk reduction of eczema in a randomized, placebo-controlled trial. J Allergy Clin Immunol. 2007 Apr;119(4):1019-21. Epub 2007 Feb 7.
• Laitinen K, Kalliomäki M, Poussa T, Lagström H, Isolauri E. Evaluation of diet and growth in children with and without atopic eczema: follow-up study from birth to 4 years. Br J Nutr. 2005 Oct;94(4):565-74.
• Land MH, Rouster-Stevens K, Woods CR, Cannon ML, Cnota J, Shetty AK. Lactobacillus sepsis associated with probiotic therapy. Pediatrics. 2005 Jan;115(1):178-81.
• Noverr MC, Noggle RM, Toews GB, Huffnagle GB. Role of antibiotics and fungal microbiota in driving pulmonary allergic responses. Infect Immun. 2004 Sep;72(9):4996-5003.
• Pessi T, Sütas Y, Hurme M, Isolauri E. Interleukin-10 generation in atopic children following oral Lactobacillus rhamnosus GG. Clin Exp Allergy. 2000 Dec;30(12):1804-8.
• Rinne M, Kalliomaki M, Arvilommi H, Salminen S, Isolauri E. Effect of probiotics and breastfeeding on the bifidobacterium and lactobacillus/enterococcus microbiota and humoral immune responses. J Pediatr. 2005 Aug;147(2):186-91.
• Von Ehrenstein OS, Von Mutius E, Illi S, Baumann L, Böhm O, von Kries R. Reduced risk of hay fever and asthma among children of farmers. Clin Exp Allergy. 2000 Feb;30(2):187-93.
• Weizman Z, Asli G, Alsheikh A. Effect of a probiotic infant formula on infections in child care centers: comparison of two probiotic agents. Pediatrics. 2005 Jan;115(1):5-9.

• Responsible Party: Mucosal Biology Research Center, Director Mucosal Biology Research Center, University of Maryland, College Park
• ClinicalTrials.gov Identifier: NCT00852124
• Other Study ID Numbers: HP-00040151; 1R21AT004089-01A1
• First Posted: Feb 26, 2009
• Last Update Posted: Jul 20, 2021
• Last Verified: Jun 1, 2021

• Keywords provided by Mucosal Biology Research Center, Director Mucosal Biology Research Center, University of Maryland, College Park: Asthma; Probiotic; VSL#3
• Additional relevant MeSH terms: Asthma

Study Results

Participant Flow

Recruitment Details	Participants were recruited between December 2010 and November 2012. Participants were recruited via flyers and newsletters.

Arm/Group Title	Placebo	VSL#3
Arm/Group Description	Packets similar to VSL#3 taken 2 X daily but not containing active bacteria VSL#3 or placebo : 1 packet 2 x daily of placebo	Packets of VSL#3 (powder containing 8 bacteria believed to be beneficial)taken 2 x daily in food or a cool beverage. VSL#3 : VSL#3 2 times daily
Period Title: Overall Study
STARTED	3	0
COMPLETED	3	0
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo	VSL#3	Total
Arm/Group Description	Packets similar to VSL#3 taken 2 X daily but not containing active bacteria VSL#3 or placebo : 1 packet 2 x daily of placebo	Packets of VSL#3 (powder containing 8 bacteria believed to be beneficial)taken 2 x daily in food or a cool beverage. VSL#3 : VSL#3 2 times daily	Total of all reporting groups
Overall Participants	3	0	3
Age (Count of Participants)
<=18 years	0 0%	0 NaN
Between 18 and 65 years	3 100%	3 Infinity
>=65 years	0 0%	0 NaN
Sex: Female, Male (Count of Participants)
Female	2 66.7%	2 Infinity
Male	1 33.3%	1 Infinity
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 NaN
Asian	0 0%	0 NaN
Native Hawaiian or Other Pacific Islander	0 0%	0 NaN
Black or African American	0 0%	0 NaN
White	3 100%	3 Infinity
More than one race	0 0%	0 NaN
Unknown or Not Reported	0 0%	0 NaN
Region of Enrollment (participants) [Number]
United States	3 100%	3 Infinity

Outcome Measures

1. Primary Outcome

Title	Safety of VSL#3 in Adults Asthmatics
Description	Change in FEV in adult asthmatics receiving VSL3# as compared to controls receiving placebo.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

3 people were randomized to placebo arm but no data were analyzed due to early termination of study and small number of patients enrolled.

Arm/Group Title	Placebo
Arm/Group Description	Packets similar to VSL#3 taken 2 X daily but not containing active bacteria VSL#3 or placebo : 1 packet 2 x daily of placebo
Measure Participants	0

Adverse Events

Time Frame	6 months
Adverse Event Reporting Description	No participants received Investigational Product. All thre particpants randomized to placebo arm. Recruitment was ended due to failure to recruit when PI relocated.
Arm/Group Title	Placebo		VSL#3
Arm/Group Description	Packets similar to VSL#3 taken 2 X daily but not containing active bacteria VSL#3 or placebo : 1 packet 2 x daily of placebo		Packets of VSL#3 (powder containing 8 bacteria believed to be beneficial)taken 2 x daily in food or a cool beverage. VSL#3 : VSL#3 2 times daily
All Cause Mortality
	Placebo		VSL#3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		VSL#3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Placebo		VSL#3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		0/0 (NaN)
Gastrointestinal disorders
Diarrhea	1/3 (33.3%)	2	0/0 (NaN)	0
Vomiting	1/3 (33.3%)	1	0/0 (NaN)	0
Infections and infestations
Fever	1/3 (33.3%)	1	0/0 (NaN)	0
Sinus Infection	2/3 (66.7%)	2	0/0 (NaN)	0
Viral illness	1/3 (33.3%)	1	0/0 (NaN)	0
Respiratory, thoracic and mediastinal disorders
Asthma exacerbation	3/3 (100%)	12	0/0 (NaN)	0

Limitations/Caveats

Early termination due to small number of persons recruited before PI relocated.

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.