Clinical trial NCT00852124: Safety of VSL#3 in Adult Asthmatics
Official title: Safety of VSL#3 for Adult Asthmatics
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Asthma
Keywords: Asthma
Probiotic
VSL#3
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: National Center for Complementary and Integrative Health (NCCIH)
First posted: 2009-02-26
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Eligibility criteria: 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.

Primary outcomes:
measure: Safety of VSL#3 in Adults Asthmatics
timeFrame: 3 months
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: University of Maryland Baltimore
state: Maryland
Study officials:
affiliation: MBRC
name: Alessio Fasano, M. D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1007/s12016-002-0012-z. No abstract available.
citation: 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. doi: 10.1136/thorax.55.9.775.
citation: Kalliomaki M, Isolauri E. Role of intestinal flora in the development of allergy. Curr Opin Allergy Clin Immunol. 2003 Feb;3(1):15-20. doi: 10.1097/00130832-200302000-00003.
citation: Bjorksten 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. doi: 10.1046/j.1365-2222.1999.00560.x.
citation: 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. doi: 10.1136/adc.2003.027680.
citation: 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.
citation: Kalliomaki 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. doi: 10.1016/j.jaci.2006.12.608. Epub 2007 Feb 7. No abstract available.
citation: Laitinen K, Kalliomaki M, Poussa T, Lagstrom 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. doi: 10.1079/bjn20051503.
citation: Von Ehrenstein OS, Von Mutius E, Illi S, Baumann L, Bohm O, von Kries R. Reduced risk of hay fever and asthma among children of farmers. Clin Exp Allergy. 2000 Feb;30(2):187-93. doi: 10.1046/j.1365-2222.2000.00801.x.
citation: 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. doi: 10.1128/IAI.72.9.4996-5003.2004.
citation: Kalliomaki 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. doi: 10.1016/S0140-6736(00)04259-8.
citation: Pessi T, Sutas 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. doi: 10.1046/j.1365-2222.2000.00948.x.
citation: Isolauri E, Sutas Y, Kankaanpaa 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.
citation: 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. doi: 10.1542/peds.2004-1815.
citation: 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. doi: 10.1542/peds.2004-2137.
citation: 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. doi: 10.1007/s10096-004-1253-y.
citation: 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. doi: 10.1016/j.jpeds.2005.03.053.