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'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 (MDCF)

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ClinicalTrials.gov Identifier: NCT03084731
Recruitment Status : Recruiting
First Posted : March 21, 2017
Last Update Posted : March 15, 2018
Sponsor:
Collaborator:
Washington University School of Medicine
Information provided by (Responsible Party):
International Centre for Diarrhoeal Disease Research, Bangladesh

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. 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. Determine whether once daily administration is as effective as twice daily administration of the lead MDCF in repairing microbiota immaturity.
  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. 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.

Methods:

Investigators will conduct 3 Pre-POC studies in 12-18 month old children with MAM (Weight-for-Length Z-score, WLZ: between <-2 to -3) and stunting (Length-for-Age Z-score, LAZ: between <-2 to -3) over the course of approximately two years. The investigators will use a stratified randomization procedure based on age (i.e.2 levels: 12-15 months and >15-18 months) to prevent imbalance between the treatment arms. This study will be undertaken at Mirpur area of Dhaka city. The investigators will design and produce 5 MDCF prototypes at the icddr,b Food Processing Laboratory in sufficient quantities for clinical studies (3 MDCF prototypes for study 1 and 2 MDCF prototypes for study 2). These formulations will be matched in energy density and micronutrient content of ready-to-use supplementary foods (RUSFs) used for MAM in Bangladesh and other countries, and will meet all other requirements for a complementary/supplementary food for 12-18 month old children with MAM and stunting.


Condition or disease Intervention/treatment Phase
Pre Proof of Concept Clinical Trial Dietary Supplement: Microbiota Directed Complementary Food (MDCF) Not Applicable

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Microbiota Directed Complementary Food (MDCF) Translational Trial
Actual Study Start Date : February 1, 2018
Estimated Primary Completion Date : February 28, 2019
Estimated Study Completion Date : February 28, 2019

Arm Intervention/treatment
Experimental: Goup 1:Children with moderate stunting and wasting
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)

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.


Experimental: Goup 2:Children with moderate stunting and wasting
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)

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.


Experimental: Goup3:Children with moderate stunting and wasting
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)

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.


No Intervention: Healthy controls
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



Primary Outcome Measures :
  1. Study 1 under main study : Treatment -induced change in MAZ score [ Time Frame: up to 5 months ]
    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)

  2. Study 2 under main study : Treatment -induced change in MAZ score [ Time Frame: upto 4 months ]
    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)

  3. Study 3 under main study: Treatment -induced change in MAZ score [ Time Frame: up to 5 months ]
    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)



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Ages Eligible for Study:   12 Months to 18 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • Medical conditions: Children with tuberculosis (diagnosis based on WHO 2014 guidelines which have been incorporated in the national TB control guidelines of Bangladesh)12 or any congenital/acquired disorder affecting growth i.e. known case of trisomy-21 or cerebral palsy; children on an exclusion diet for the treatment of persistent diarrhea; having known history of soy, peanut or milk protein allergy.
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03084731


Contacts
Contact: Tahmeed Ahmed, PhD +88-02-9827103 ext 2300 tahmeed@icddrb.org
Contact: Md.Munirul Islam, PhD +88-02-9827001 ext 2352 mislam@icddrb.org

Locations
Bangladesh
Mirpur Recruiting
Dhaka, Bangladesh, 1216
Contact: Tahmeed Ahmed, Ph.D    +88029827001-10 ext 2300    tahmeed@icddrb.org   
Contact: Mustafa Mustafa, MPH    9840523-32 ext 2304    mustafa@icddrb.org   
Principal Investigator: Mustafa Mustafa, MPH         
Sponsors and Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh
Washington University School of Medicine

Responsible Party: International Centre for Diarrhoeal Disease Research, Bangladesh
ClinicalTrials.gov Identifier: NCT03084731     History of Changes
Other Study ID Numbers: 16099
First Posted: March 21, 2017    Key Record Dates
Last Update Posted: March 15, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by International Centre for Diarrhoeal Disease Research, Bangladesh:
Microbiota
Complementary Food