'Pre-Proof of Concept (Pre-POC)' Clinical Trials to Optimize Lead Microbiota-directed Complementary Food (MDCF) Prototypes for Their Ability to Repair Microbiota Immaturity and Establish Their Organoleptic Acceptability

NCT03084731 | Unknown

• 1 other identifier: PR-16099
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

Burden: According to Bangladesh Demographic Health Survey 2014, prevalence of stunting in under-five children is 36%. Severe acute malnutrition (SAM) is prevalent in about 3% of them. In absolute numbers, about 450,000 children suffer from SAM while several million children suffer from moderate acute malnutrition (MAM). Knowledge gap: Investigators have already demonstrated that children with SAM have immature gut microbiota that is partially corrected with treatment. Through our earlier studies conducted in Bangladesh,investigators now also have idea about beneficial microbiota and food ingredients that support proliferation of these beneficial microbiota. Which composite food is better for children with SAM and MAM is not known. Hypothesis (if any): The central hypothesis of our ongoing Breast Milk, Gut Microbiome and Immunity (BMMI) initiative proof of concept phase is that healthy growth in infancy and early childhood requires normal functional maturation of the gut microbiota. Related hypotheses are that (i) persistent defects in the development of this microbial 'organ' are causally related to stunting as well as the metabolic, immunologic and cognitive manifestations of undernutrition; and (ii) new approaches for durable repair of this microbiota immaturity including Microbiota-Directed Complementary Foods (MDCF) will provide a way to improve clinical outcomes. Objectives:

1. 1.Test 5 MDCF prototypes and nominate a lead MDCF formulation that has the greatest effect in promoting the representation of a broad range of age-discriminatory taxa and that has acceptable organoleptic properties. This nominated lead will be advanced to a fully powered clinical POC study in children with post-SAM MAM in 2018.
2. 2.Determine whether once daily administration is as effective as twice daily administration of the lead MDCF in repairing microbiota immaturity.
3. 3.Assess the durability of repair of immaturity by the lead MDCF by including a 4 week post-intervention phase in the final pre-POC study design.
4. 4.Determine what effect enteropathogen burden (determined by PCR-based analysis of fecal samples) has on responses of age-discriminatory taxa to MDCFs, and reciprocally, the effect of MDCFs on enteropathogen burden.

Conditions

Pre Proof of Concept Clinical Trial

Keywords

Microbiota; Complementary Food

Outcome Measures

Primary Outcomes (3)

• Study 1 under main study : Treatment -induced change in MAZ score

  MAZ Score=(microbiota age-median microbiota age of healthy children of same chronologic age)/(standard deviation of microbiota age of healthy children of the same chronologic age)

  up to 5 months

• Study 2 under main study : Treatment -induced change in MAZ score

  MAZ Score=(microbiota age-median microbiota age of healthy children of same chronologic age)/(standard deviation of microbiota age of healthy children of the same chronologic age)

  upto 4 months

• Study 3 under main study: Treatment -induced change in MAZ score

  MAZ Score=(microbiota age-median microbiota age of healthy children of same chronologic age)/(standard deviation of microbiota age of healthy children of the same chronologic age)

  up to 5 months

Study Arms (4)

Goup 1:Children with moderate stunting and wasting

EXPERIMENTAL

Test 3 prototype MDCFs and the current rice-lentil RUSF standard of care for MAM to establish the effect size of each on MAZ repair in a 4 week 2x /day intervention, with a 2 week post-intervention phase to assess durability of MDCF-induced changes in the microbiota.

Dietary Supplement: Microbiota Directed Complementary Food (MDCF)

Goup 2:Children with moderate stunting and wasting

EXPERIMENTAL

Select most efficacious MDCF from study 1 and compare with 2 additional MDCF prototypes using the same design used in study 1.

Dietary Supplement: Microbiota Directed Complementary Food (MDCF)

Goup3:Children with moderate stunting and wasting

EXPERIMENTAL

Select lead MDCF from studies 1, 2 and conduct final 'bake-off' vs current RUSF and also examine the impact of 1x vs 2x per day administration with a 4 week post-intervention period to provide additional information on the durability of MDCF-sponsored changes in the microbiota.

Dietary Supplement: Microbiota Directed Complementary Food (MDCF)

Healthy controls

NO INTERVENTION

In order to construct a library of gut microbiota of healthy growing children of the same community, one spot fecal sample (1-2 gm) and spot blood sample (2 mL) will be collected from 30 children each who would be aged 12-18 months of either sex, having WLZ and LAZ : \>-1

Interventions

Microbiota Directed Complementary Food (MDCF) DIETARY_SUPPLEMENT

For Study 1: Investigators will test 3 prototype MDCFs and the current RUSF standard of care for MAM to establish the effect size of each on MAZ repair in a 4 week twice daily intervention, with a 2 week post-intervention phase. Study 2: From study 1 Investigators will select most efficacious MDCF and compare with 2 additional MDCF prototypes to establish the effect size of each on MAZ repair in a 4 week twice daily intervention, with a 2 week post-intervention phase. Study 3: Investigators will select the lead MDCF from study 2 and examine the effects between the final MDCF versus current RUSF and also examine the impact dispensing of the lead MDCF once versus twice per day with a 4 week post-intervention period.

Goup 1:Children with moderate stunting and wasting; Goup 2:Children with moderate stunting and wasting; Goup3:Children with moderate stunting and wasting

Eligibility Criteria

• Age: 12 Months - 18 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• All of the following criteria must be met for a study participant to be eligible to participate in the study -
• Parent(s) willing to sign consent form
• Child age 12-18 months and no longer exclusively breast fed
• WLZ between \<-2 and -3; LAZ: between \<-2 and -3
• Parent(s) willing to bring child to the feeding centre twice daily for 4 weeks for nutritional therapy and provide weekly fecal samples from their child for the duration of the study. The informed consent document will explicitly request permission to use the collected fecal samples for future studies, including but not limited to culturing component bacterial strains.

You may not qualify if:

• Febrile illness or antibiotic use within the last 30 days
• Receiving concurrent treatment for another condition
• Any known history of or screened positive for clotting disorders or severe anaemia (\<8mg/dl)
• Failure to obtain informed written consent from parents or caretakers

Sponsors & Collaborators

• International Centre for Diarrhoeal Disease Research, Bangladesh: lead
• Washington University School of Medicine: collaborator

Study Sites (1)

Mirpur

Dhaka, 1216, Bangladesh

RECRUITING

Central Study Contacts

Tahmeed Ahmed, PhD

CONTACT

+88-02-9827103; tahmeed@icddrb.org

Md.Munirul Islam, PhD

CONTACT

+88-02-9827001; mislam@icddrb.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2017
• First Posted: March 21, 2017
• Study Start: February 1, 2018
• Primary Completion: November 28, 2022
• Study Completion: November 28, 2022
• Last Updated: February 11, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

BA (1)