Transfer of Healthy Gut Flora for Restoration of Intestinal Microbiota Via Enema for Patients in the Rehabilitative Phase of Malnutrition

NCT03087097 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: THRIVE001
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This single-center, randomized, open-label trial will compare the safety of MTT delivered by rectal catheter enema in participants 12-60 months of age with malnutrition (moderate acute malnutrition \[MAM\] or severe acute malnutrition \[SAM\]) who are in the rehabilitative phase of treatment and have failed to respond to at least 4 weeks of standard therapy. Participants must meet inclusion criteria, no exclusion criteria prior to randomization. Participants will then be randomized in a 1:1 ratio at each site to 1 of 2 treatment groups:

• MTT by rectal catheter enema: 10mL/kg (maximum 150mL, +/- 5ml) of healthy donor human intestinal microbiota will be infused.
• Standard of care treatment for malnutrition as prescribed by local and national Department of Health Guidelines Participants will be evaluated through 56 days (±3) after randomization for primary outcomes (safety) as well as secondary outcomes (nutritional, clinical and microbiological response). Participant blood and urine samples will be collected at enrollment and day 56. Participant stool samples will be collected at enrollment and through days 3, 7, 21 and 56, thereafter, 3 months, 4 months, and 6 months. A caregiver stool sample will be collected at enrollment and day 56. Samples will be used for microbiome determination and other exploratory microbiological endpoints. An aliquot of donor stool will also be stored for microbiome determination and other exploratory microbiological endpoints and assessment of newly acquired infectious agents.

Conditions

Severe Acute Malnutrition; Moderate Acute Malnutrition

Keywords

SAM; MAM

Outcome Measures

Primary Outcomes (1)

• Serious Adverse Events

  Number of participants with an Adverse Event grade 2 or above up to 56 days post-treatment

  56 days

Secondary Outcomes (4)

• Nutritional recovery:

  56 days

• Clinical:

  56 days

• Microbiological:

  56 Days

• Translational:

  56 Days

Study Arms (2)

Fecal Microbiota Transplant

EXPERIMENTAL

FMT by enema: 10mL/kg (maximum 150mL) of healthy donor human intestinal microbiota will be infused.

Biological: Fecal Microbiota Transplantation

Standard of Care

NO INTERVENTION

Standard of care treatment for malnutrition as prescribed by local and national Department of Health Guidelines

Interventions

Fecal Microbiota Transplantation BIOLOGICAL

Fecal microbiota delivered by rectal catheter enema in participants 12-60 months of age with malnutrition (MAM or SAM) who are in the rehabilitation phase of treatment and have failed to respond to at least 4 weeks of standard therapy.

Also known as: Microbiota transfer therapy (MTT)

Fecal Microbiota Transplant

Eligibility Criteria

• Age: 12 Months - 60 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 12 to 60 months.
• Current diagnosis of malnutrition (defined as a WHZ less than -2 according to the WHO 2006 standards or a MUAC less than 125mm) with failure to respond nutritionally, defined as:
• a. A WHZ of less than -2 according or a mid-upper-arm circumference of less than 125 mm i. No medical complications present ii. Participant is sufficiently alert and successfully passes the appetite test which involves consumption of breastmilk or a ready to use therapeutic food (RUTF) under supervision.
• iii. Participant is in the rehabilitation phase of treatment for malnutrition
• HIV negative
• Received at last four weeks of optimal WHO treatment for malnutrition:
• Micronutrient supplementation (Vitamin A, zinc and iron) as recommended by local guidelines
• Nutritional rehabilitation as recommended by local guidelines.
• Written informed consent obtained by parent or caregiver.

You may not qualify if:

• Evidence of current complicated malnutrition defined as any of the following:
• Admitted to acute care ward as inpatient
• One or more WHO Integrated Management of Childhood Illness danger signs.(3)
• Failure to pass appetite test.
• Presence of known comorbid diseases such as pulmonary Tuberculosis on treatment, cystic fibrosis, type I diabetes mellitus, intestinal malabsorptive syndromes, chronic lung disease, chronic liver disease, chronic renal disease, chronic neurological diseases (e.g. cerebral palsy) or malignancy undergoing active chemotherapy.
• Bilateral pitting pedal edema or generalized anasarca
• Have taken antibiotics in the past seven days before the Day 0 visit or are anticipated to need antibiotics up to seven days before the Day 0 visit.
• Congenital malformations, syndromic conditions, and congenital metabolic abnormalities (inborn errors of metabolism) that may adversely affect growth and in the view of the clinician, exposes the child to increased risk.
• Presence of bilateral pitting edema Grade 2.
• Contraindications to rectal catheter enema:
• Anorectal malformations
• Rectal prolapse
• Hirschsprungs disease
• Other contraindication to enema.
• Primary immune deficiencies

Sponsors & Collaborators

• Microbiome Health Research Institute: lead
• University of Cape Town: collaborator

Study Sites (1)

University of Cape Town

Cape Town, South Africa

Location

MeSH Terms

Conditions

Severe Acute Malnutrition

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Majdi A Osman, MD MPH

  Microbiome Health Research Institute

  PRINCIPAL INVESTIGATOR

• Shrish Budree, MD MBChB DCH FCPeds

  Microbiome Health Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2016
• First Posted: March 22, 2017
• Study Start: April 11, 2019
• Primary Completion: July 21, 2020
• Study Completion: July 21, 2020
• Last Updated: January 13, 2021

Record last verified: 2021-01

Locations

ZA (1)