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

NCT04015999 | Unknown Phase 2 DMC

• 1 other identifier: PR-18073
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 1

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

Conditions

Microbiota; Complementary Food; Nutrition

Outcome Measures

Primary Outcomes (5)

• Change in Ponderal growth

  Rate of weight gain of the enrolled participants

  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

• Change in Linear growth (LAZ),

  Rate of skeletal human growth

  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

• Change in Proteomic profile

  Information about all proteins that are made in blood, other body fluids, or tissues, at certain times. It will be assayed by Somalogic scan.

  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.

• Change in Morbidity

  Refers to having a disease or a symptom of disease. It will be assessed by taking morbidity data.

  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.

• Change in microbiota-for-age Z score

  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.

  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.

Study Arms (2)

Intervention arm

EXPERIMENTAL

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)

Control arm

ACTIVE COMPARATOR

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)

Interventions

Microbiota Directed Complementary Food (MDCF) DIETARY_SUPPLEMENT

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)

Intervention arm

Ready to Use Supplementary Food (RUSF) DIETARY_SUPPLEMENT

Rice-lentil based RUSF (rationale: reference standard of care for MAM; based on knowledge of its effects on the gut microbiota or microbiota immaturity)

Control arm

Eligibility Criteria

• Age: 12 Months - 18 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Icddr,B

Dhaka, 1212, Bangladesh

RECRUITING

Related Publications (13)

• 1. Hawkes C. Global nutrition report 2017: Nourishing the SDGs. Development Initiatives; 2017.

  BACKGROUND

• James P, Sadler K, Wondafrash M, Argaw A, Luo H, Geleta B, Kedir K, Getnet Y, Belachew T, Bahwere P. Children with Moderate Acute Malnutrition with No Access to Supplementary Feeding Programmes Experience High Rates of Deterioration and No Improvement: Results from a Prospective Cohort Study in Rural Ethiopia. PLoS One. 2016 Apr 21;11(4):e0153530. doi: 10.1371/journal.pone.0153530. eCollection 2016.

  PMID: 27100177 BACKGROUND

• 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.

  BACKGROUND

• 4. Save the children (2015), malnutrition in Bangladesh: Harnessing social protection for the most vulnerable (2015).

  BACKGROUND

• Blanton LV, Barratt MJ, Charbonneau MR, Ahmed T, Gordon JI. Childhood undernutrition, the gut microbiota, and microbiota-directed therapeutics. Science. 2016 Jun 24;352(6293):1533. doi: 10.1126/science.aad9359.

  PMID: 27339978 BACKGROUND

• Subramanian S, Huq S, Yatsunenko T, Haque R, Mahfuz M, Alam MA, Benezra A, DeStefano J, Meier MF, Muegge BD, Barratt MJ, VanArendonk LG, Zhang Q, Province MA, Petri WA Jr, Ahmed T, Gordon JI. Persistent gut microbiota immaturity in malnourished Bangladeshi children. Nature. 2014 Jun 19;510(7505):417-21. doi: 10.1038/nature13421. Epub 2014 Jun 4.

  PMID: 24896187 BACKGROUND

• Choudhury N, Ahmed T, Hossain MI, Islam MM, Sarker SA, Zeilani M, Clemens JD. Ready-to-Use Therapeutic Food Made From Locally Available Food Ingredients Is Well Accepted by Children Having Severe Acute Malnutrition in Bangladesh. Food Nutr Bull. 2018 Mar;39(1):116-126. doi: 10.1177/0379572117743929. Epub 2017 Dec 19.

  PMID: 29258336 BACKGROUND

• Yan J, Herzog JW, Tsang K, Brennan CA, Bower MA, Garrett WS, Sartor BR, Aliprantis AO, Charles JF. Gut microbiota induce IGF-1 and promote bone formation and growth. Proc Natl Acad Sci U S A. 2016 Nov 22;113(47):E7554-E7563. doi: 10.1073/pnas.1607235113. Epub 2016 Nov 7.

  PMID: 27821775 BACKGROUND

• MAL-ED Network Investigators. Childhood stunting in relation to the pre- and postnatal environment during the first 2 years of life: The MAL-ED longitudinal birth cohort study. PLoS Med. 2017 Oct 25;14(10):e1002408. doi: 10.1371/journal.pmed.1002408. eCollection 2017 Oct.

  PMID: 29069076 BACKGROUND

• 10. World Health Organization. World health statistics 2016: monitoring health for the SDGs sustainable development goals. World Health Organization; 2016 Jun 8.

  BACKGROUND

• de Onis M, Garza C, Victora CG, Onyango AW, Frongillo EA, Martines J. The WHO Multicentre Growth Reference Study: planning, study design, and methodology. Food Nutr Bull. 2004 Mar;25(1 Suppl):S15-26. doi: 10.1177/15648265040251S103.

  PMID: 15069916 BACKGROUND

• Chen RY, Mostafa I, Hibberd MC, Das S, Mahfuz M, Naila NN, Islam MM, Huq S, Alam MA, Zaman MU, Raman AS, Webber D, Zhou C, Sundaresan V, Ahsan K, Meier MF, Barratt MJ, Ahmed T, Gordon JI. A Microbiota-Directed Food Intervention for Undernourished Children. N Engl J Med. 2021 Apr 22;384(16):1517-1528. doi: 10.1056/NEJMoa2023294. Epub 2021 Apr 7.

  PMID: 33826814 DERIVED

• Mostafa I, Nahar NN, Islam MM, Huq S, Mustafa M, Barratt M, Gordon JI, Ahmed T. Proof-of-concept study of the efficacy of a microbiota-directed complementary food formulation (MDCF) for treating moderate acute malnutrition. BMC Public Health. 2020 Feb 17;20(1):242. doi: 10.1186/s12889-020-8330-8.

  PMID: 32066412 DERIVED

Study Officials

• Tahmeed Ahmed, PhD, MBBS

  Senior Director, Nutrition & Clinical Services Division, icddr,b

  PRINCIPAL INVESTIGATOR

• 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

  STUDY CHAIR

Central Study Contacts

Tahmeed Ahmed, PhD, MBBS

CONTACT

01713044799; tahmeed@icddrb.org

Mustafa Mahfuz, MPH, MBBS

CONTACT

01712214205; mustafa.mahfuz@icddrb.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2019
• First Posted: July 11, 2019
• Study Start: November 1, 2018
• Primary Completion: June 28, 2021
• Study Completion: June 28, 2021
• Last Updated: July 21, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

BA (1)