Clinical trial NCT01130792: Probiotics for Infectious Diarrhea in Children in South India
Official title: Probiotics for Infectious Diarrhea in Children in South India
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Infectious Gastroenteritis
Keywords: rotavirus
cryptosporidium
probiotics
intestinal function
immune response
Lead sponsor: Christian Medical College, Vellore, India
Sponsor class: OTHER
Collaborators: name: Indian Council of Medical Research
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Tufts Medical Center
First posted: 2010-05-26
Enrollment: 124
Sex: ALL
Minimum age (years): 6
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: The overall goal of this study is to investigate whether the modulatory effects of probiotics, which are used as food supplements (Lactobacillus GG marketed as Culturelle or yoghurt) in the gastrointestinal tract promote restoration of intestinal function and enhance the specific immune response in children with cryptosporidial or rotaviral infections in South India. Rotavirus and Cryptosporidium spp. are the most important viral and parasitic causes of gastroenteritis in children in south India. Both infections can lead to severe dehydrating gastroenteritis in young children and have no specific treatment. Repeated episodes of diarrhea can result in long term deleterious effects on nutritional status, possibly due to intestinal damage. Most episodes of infectious gastroenteritis resolve without specific therapy, the mainstay of treatment being rehydration. However, oral rehydration remains under-utilized, in part due to the lack of effect on frequency of bowel movements and duration of illness. Due to the interest in simple, safe and effective measures to ameliorate the long-term effects of diarrheal illness, there is a growing appreciation for the potential of certain microorganisms to offer direct benefits to the health of a host. Probiotics are known to beneficially modulate several host functions, the most important of which are immune responses and intestinal barrier integrity. The investigators propose to build on the investigators previous collaborative efforts to conduct pilot studies to provide a mechanistic understanding of the effect of probiotic supplementation in children with rotaviral and cryptosporidial diarrhea.

Based on the established efficacy of LGG for the treatment of a variety of diarrheal diseases and the documented modulation of immune responses and strengthening of intestinal epithelial barrier function by probiotics, the investigators propose to conduct a Phase I/II double-blind randomized placebo controlled clinical trial to assess the preliminary efficacy and safety of LGG vs. placebo in the resolution of symptoms and restoration of intestinal function in children with either rotaviral or cryptosporidial diarrhea and no other detected enteric infection. Promising results in this Phase I/II study will provide preliminary data to power a future randomized trial on these critical outcomes following rotaviral or cryptosporidial infection.


Eligibility criteria: Inclusion Criteria:

* Male and female children aged 6 months to 5 years
* Diagnosis of rotaviral or cryptosporidial gastroenteritis (Rotavirus or
* Cryptosporidium EIA positive and three or more watery stools within a 24-hour period)
* No other enteric pathogen isolated from the stool at the time of enrollment
* Able to take the contents of study capsules mixed into food or milk
* No need for antibiotics for current illness
* No use of LGG/other probiotics within 30 days (yogurt consumption is not an exclusion criterion)
* HIV negative
* No severe malnutrition (WAZ score \< 3SD below the median)
* No evidence of active bowel leak, acute abdomen or colitis
* No history of allergy
* Parent/guardian willing to report on compliance and side effects during the study period
* Families willing to provide informed consent, participate in study and have study personnel visit their home.

Exclusion criteria

* Other enteric pathogens isolated from the stool at the time of enrollment
* Not willing or able to take the contents of study capsules mixed into food or milk
* Need for antibiotics for current illness
* HIV positive
* Severe malnutrition (WAZ score \< 3SD below the median)
* Presence of active bowel leak, acute abdomen or colitis
* History of allergy
* Parent/guardian not willing to report on compliance and side effects during the study period
* Families not willing to provide informed consent, participate in study or have study personnel visit their home.

Primary outcomes:
measure: IgG To Rotavirus VP6 Or Cryptosporidial Gp15
timeFrame: 4 weeks
Secondary outcomes:
measure: lactulose:mannitol test
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Vellore
country: India
facility: Christian Medical College
state: Tamil Nadu
Study officials:
affiliation: Christian Medical College, Vellore, India
name: Gagandeep Kang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tufts Medical Center
name: Honorine D Ward, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sindhu KN, Sowmyanarayanan TV, Paul A, Babji S, Ajjampur SS, Priyadarshini S, Sarkar R, Balasubramanian KA, Wanke CA, Ward HD, Kang G. Immune response and intestinal permeability in children with acute gastroenteritis treated with Lactobacillus rhamnosus GG: a randomized, double-blind, placebo-controlled trial. Clin Infect Dis. 2014 Apr;58(8):1107-15. doi: 10.1093/cid/ciu065. Epub 2014 Feb 5.