Clinical trial NCT00937274: Antibacterial Treatment Against Diarrhea in Oral Rehydration Solution
Official title: Randomized, Double Blind Placebo-controlled Studies to Evaluate the Effect of an Orally-fed Escherichia Coli (E. Coli) Phage in the Management of ETEC and EPEC Induced Diarrhea in Children
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Diarrhea
Keywords: ETEC EPEC diarrhoea
phage therapy
ORS
Lead sponsor: Société des Produits Nestlé (SPN)
Sponsor class: INDUSTRY
First posted: 2009-07-10
Enrollment: 120
Sex: MALE
Minimum age (years): 6
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study hopes to demonstrate the potentials of a new form of therapy for childhood diarrhea, a major cause of morbidity and deaths in Bangladesh and other developing countries, and thus a priority for improving child health.

Detailed description: This randomized double-blind, placebo controlled trial (RCT) aims to evaluate the effect of oral administered E. coli phage in children aged 4-60 months of age with proven ETEC and EPEC diarrhea. Children will be screened to exclude V. cholerae infections by dark field microscopy, rotavirus by stool ELISA, and invasive diarrhoea clinically as well as by stool microscopy, to identify children with possible ETEC and EPEC diarrhoea. Enrolled children will be randomly assigned, in equal numbers, to receive either: (i) a new T4 phage cocktail or (ii) Russian anti-E. coli phage cocktail (Microgen) at the dose recommended by the manufacturer or (iii) only oral rehydration solution (placebo) for 5 days in addition to management of dehydration and continued feeding in accordance with WHO guidelines. Duration of diarrhea, daily and cumulative stool output, volume of oral rehydration solution intake, stool frequency, time to recovery and weight gain will be the main outcome measures. As the dose of phage we intend to use in this therapeutic trial is higher than the dose administered to young children in earlier safety trial, we plan to initially conduct a safety study with these three study products in 45 children with non cholera, non rotavirus and non invasive diarrhea, to randomize equally in the three intervention groups, as for the final study mentioned above. The outcome measures in this safety part will include assessment of laboratory parameters including renal and liver function tests, haematological indices, and microbiological efficacy of phage by measuring phage and E. coli titre in daily stool samples. If the higher dose is found safe, tolerable, and not associated with any significant adverse event, we will proceed to the clinical efficacy trial.

We believe if T4 coli phage is assessed to be effective in the overall diarrhea management, this might lead to development of an affordable and sustainable adjunct to the currently available case management of E. coli diarrhea, benefiting millions of children worldwide.

Eligibility criteria: Inclusion Criteria:

1. Sex: male
2. Age: 6 - 24 months
3. Better nourished (weight for age \> 60 NCHS median)
4. H/o. diarrhea of less than 48 hours
5. Written informed consent from either parents/guardian (thumb impression for those who are not literate) for children
6. Negative test results for dark field microscopy of Vibrio cholerae and ELISA test for rotavirus in initial stool samples

Exclusion Criteria:

1. Systemic infection requiring antibiotic treatment
2. Severe malnutrition (W/A \< 60%)
3. Unwilling to comply with study procedures
4. Currently participating or have participated in another clinical trial within the last 4 weeks at screening
5. Clinically significant abnormalities from medical history, physical examination, vital signs, haematology, clinical chemistry results, or other laboratory abnormalities
6. Clinically suggestive of invasive diarrhea

Primary outcomes:
measure: Assessment of safety, tolerability and efficacy (reduce severity of diarrhea assessed by reduced stool volume and stool frequency) of oral administration of T4 phages in young children with diarrhea due to ETEC and/or EPEC infections
timeFrame: 5 days
Secondary outcomes:
measure: Clinical assessment, blood tests, morbidity, duration of hospitalization
timeFrame: 5 days
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: Clinical Sciences Division, ICDDR,B, Mohakhali,
Study officials:
affiliation: Clinical Sciences Division, ICDDR,B, Mohakhali, Dhaka 1212, Bangladesh
name: Shafiqul A Sarker, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sarker SA, Sultana S, Reuteler G, Moine D, Descombes P, Charton F, Bourdin G, McCallin S, Ngom-Bru C, Neville T, Akter M, Huq S, Qadri F, Talukdar K, Kassam M, Delley M, Loiseau C, Deng Y, El Aidy S, Berger B, Brussow H. Oral Phage Therapy of Acute Bacterial Diarrhea With Two Coliphage Preparations: A Randomized Trial in Children From Bangladesh. EBioMedicine. 2016 Jan 5;4:124-37. doi: 10.1016/j.ebiom.2015.12.023. eCollection 2016 Feb.