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Community-based Clinical Trial With Microbiota-directed Complementary Foods (MDCFs) Made of Locally Available Food Ingredients for the Management of Children With Primary Moderate Acute Malnutrition

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ClinicalTrials.gov Identifier: NCT04015999
Recruitment Status : Recruiting
First Posted : July 11, 2019
Last Update Posted : July 21, 2020
Sponsor:
Collaborator:
Washington University School of Medicine
Information provided by (Responsible Party):
International Centre for Diarrhoeal Disease Research, Bangladesh

Brief Summary:

Background (brief):

Burden: A total of 52 million children under 5 are suffering from acute malnutrition globally, of whom 33 million have moderate acute malnutrition (MAM). In Bangladesh, more than 2 million children suffer from MAM. According to Bangladesh Demographic Health Survey 2014 26%, 25% and 17% of children aged less than two years are stunted, underweight and wasted respectively.

Knowledge gap: It has been already demonstrated that children with SAM have immature gut microbiota that is partially corrected with treatment. Children with MAM have an increased risk of mortality, infections and impaired physical and cognitive development compared to well-nourished children. Although the global caseload of MAM is much greater than that of SAM, the condition has not received the same level of attention or priority. Through our previous and ongoing research we now know about the members of the gut microbiota that can promote growth in children and also about certain food ingredients that promote the proliferation of such beneficial microbiota. However, this knowledge needs to be applied on a sufficiently powered community-based clinical trial.

Relevance: The rationale for this study is to assess whether long-term administration of complementary food made of locally available food ingredients can stimulate the proliferation of growth promoting members of the gut microbiota and have a positive impact on child growth. Such a food (the microbiota directed complementary food; MDCF-2) has been identified through our recently concluded Pre-proof of concept trial done on children with primary MAM. We would now like to do a clinical community-based trial of this potential MDCF-2 in the management of children with primary MAM.

Hypothesis: Complementary foods made of locally available food ingredients that stimulate the proliferation of growth promoting gut microbiota (MDCF-2) will improve clinical outcomes.

Methods: We will conduct a proof of concept (POC) clinical trial in 12-18 months old children with primary MAM (Weight-for-Length Z-score, WLZ between -2 and -3). This study will be conducted at Bauniabadh, Radda MCH-FP (Maternal and Child Health- Family Planning) clinic, Gabtoli of Mirpur area and possibly at the Special Nutrition Unit run by Terre des Hommes in Kurigram. We will produce MDCF-2 at the icddr,b Food Processing Laboratory or nutrition centre established at the site in sufficient quantities for clinical study. This formulation 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 months old children with MAM. We will test MDCF-2 and the current RUSF standard of care for primary MAM to see the effect on growth, proteomics and metabolomics of an intervention for 12 weeks, with a 4-week post-intervention phase.

Hypothesis to be tested:

In a hypothesis testing research proposal, briefly mention the hypothesis to be tested and provide the scientific basis of the hypothesis, critically examining the observations leading to the formulation of the hypothesis.

Complementary foods made of locally available food ingredients that stimulate the proliferation of growth promoting gut microbiota (MDCF) will provide a new way to improve clinical outcomes, for example by improving growth of children with MAM.

Specific Objectives:

To investigate the efficacy of complementary food made of locally available food ingredients that can stimulate the proliferation of growth promoting gut microbiota (Microbiota-Directed Complementary Food; MDCF-2) in (i) promoting repair of microbiota immaturity (ii) promoting proliferation of beneficial bacteria (iii) improving both ponderal and linear growth in children (iv) improving the metabolomic profile with MAM


Condition or disease Intervention/treatment Phase
Microbiota Complementary Food Nutrition Dietary Supplement: Microbiota Directed Complementary Food (MDCF) Dietary Supplement: Ready to Use Supplementary Food (RUSF) Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 124 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Microbiota-directed Complementary Food (MDCF) Trial
Actual Study Start Date : November 1, 2018
Estimated Primary Completion Date : June 28, 2021
Estimated Study Completion Date : June 28, 2021

Arm Intervention/treatment
Experimental: Intervention arm
MDCF2 with four complementary food ingredients (rationale: lead with evidence from Pre-POC clinical trials to optimize lead microbiota-directed complementary food prototypes for their ability to repair microbiota immaturity and positive effects on growth)
Dietary Supplement: Microbiota Directed Complementary Food (MDCF)
MDCF2 with four complementary food ingredients (rationale: lead with evidence from Pre-POC clinical trials to optimize lead microbiota-directed complementary food prototypes for their ability to repair microbiota immaturity and positive effects on growth)

Active Comparator: Control arm
Rice-lentil based RUSF (rationale: reference standard of care for MAM; based on knowledge of its effects on the gut microbiota or microbiota immaturity)
Dietary Supplement: Ready to Use Supplementary Food (RUSF)
Rice-lentil based RUSF (rationale: reference standard of care for MAM; based on knowledge of its effects on the gut microbiota or microbiota immaturity)




Primary Outcome Measures :
  1. Change in Ponderal growth [ Time Frame: At the enrollment (day1), every 15 days during the 3 months of intervention phase and at the end of 1 month of follow up phase by anthropometry ]
    Rate of weight gain of the enrolled participants

  2. Change in Linear growth (LAZ), [ Time Frame: At the enrollment (day1), every 15 days during the 3 months of intervention phase and at the end of q month of follow up phase by anthropometry ]
    Rate of skeletal human growth

  3. Change in Proteomic profile [ Time Frame: A total of 3 Plasma samples will be collected, just before the start of intervention phase, at the end of first month of intervention phase and just after the completion of 3rd month. ]
    Information about all proteins that are made in blood, other body fluids, or tissues, at certain times. It will be assayed by Somalogic scan.

  4. Change in Morbidity [ Time Frame: Data will be collected every day during the 3 months of intervention phase and once at the end of 1 month of follow up phase. ]
    Refers to having a disease or a symptom of disease. It will be assessed by taking morbidity data.

  5. Change in microbiota-for-age Z score [ Time Frame: At the enrollment, at the beginning of the intervention phase, weekly during the 1st month of intervention, at the end of 2nd and 3rd months of intervention and at the end of 1 month of follow up phase. ]
    Bacterial species whose proportional representation define a healthy gut microbiota as it assembles during the first two postnatal years of life.'Microbiota-for-age-Z-score' compares development of a child's fecal microbiota relative to healthy children of similar chronologic age.



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Months to 18 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Parent(s) willing to sign consent form
  • Child age 12-18 months and no longer exclusively breast fed
  • WLZ (<-2 to -3) without bilateral pedal edema at the time of randomization
  • Parent(s) willing to bring the child to the feeding center twice daily for 4 weeks for nutritional therapy, once daily for next 4 weeks and provide feeding once daily at home for 4 weeks and twice daily for next 4 weeks.
  • 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). The guidelines depend upon the following five diagnostic principles (three out of five should be positive): 1. Specific symptoms of TB, 2. Specific signs, 3. Chest X-ray, 4. Mantoux test, and 5. History of contact. 10 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
  • Antibiotic use within the last 15 days
  • Receiving concurrent treatment for another condition
  • Severe anemia (<8mg/dl) will be assessed by Hemocue (Model no. Hemocue Hb 301)
  • 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): NCT04015999


Contacts
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Contact: Tahmeed Ahmed, PhD, MBBS 01713044799 ext 2300 tahmeed@icddrb.org
Contact: Mustafa Mahfuz, MPH, MBBS 01712214205 ext 2304 mustafa.mahfuz@icddrb.org

Locations
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Bangladesh
Icddr,B Recruiting
Dhaka, Bangladesh, 1212
Contact: Tahmeed Ahmed, PhD, MBBS    01713044799 ext 2300    tahmeed@icddrb.org   
Contact: Mustafa Mahfuz, MPH, MBBS    01712214205 ext 2304    mustafa.mahfuz@icddrb.org   
Sponsors and Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh
Washington University School of Medicine
Investigators
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Principal Investigator: Tahmeed Ahmed, PhD, MBBS Senior Director, Nutrition & Clinical Services Division, icddr,b
Study Chair: Munirul Islam, PhD, MBBS Scientist, Nutrition and Clinical Services Division, icddr,b
Study Chair: Mustafa Mahfuz, MPH, MBBS Associate scientist, Nutrition and Clinical Services Division, icddr,b
Study Chair: Sayeeda Haque, MPH, MBBS Associate Scientist, Consultant Physician, Nutrition Ward, Nutrition & Clinical Services Division, icddr,b
Study Chair: Ishita Mostafa, MPH, MBBS Research Investigator, Nutrition & Clinical Services Division, icddr,b
Study Chair: Imteaz Mahmud, MBBS Research Fellow, Nutrition & Clinical Services Division, icddr,b
Study Chair: Nurun Nahar Naila, MPH, MBBS Assistant scientist, Nutrition & Clinical Services Division, icddr,b
Publications:
1. Hawkes C. Global nutrition report 2017: Nourishing the SDGs. Development Initiatives; 2017.
3. National Institute of Population Research and Training (NIPORT), Mitra and Associates, and ICF International. 2016. Bangladesh Demographic and Health Survey 2014. Dhaka, Bangladesh, and Rockville, Maryland, USA: NIPORT, Mitra and Associates, and ICF International.
4. Save the children (2015), malnutrition in Bangladesh: Harnessing social protection for the most vulnerable (2015).
10. World Health Organization. World health statistics 2016: monitoring health for the SDGs sustainable development goals. World Health Organization; 2016 Jun 8.
11. de Onis M, Garza C, Victora CG, Bhan MK, and Norum KR. The WHO Multicentre Growth Reference Study (MGRS): Rationale, planning, and implementation. Food and Nutrition Bulletin 2004;25(supplement 1):S3-S84.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: International Centre for Diarrhoeal Disease Research, Bangladesh
ClinicalTrials.gov Identifier: NCT04015999    
Other Study ID Numbers: PR-18073
First Posted: July 11, 2019    Key Record Dates
Last Update Posted: July 21, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes