Clinical trial NCT03087097: Transfer of Healthy Gut Flora for Restoration of Intestinal Microbiota Via Enema for Patients in the Rehabilitative Phase of Malnutrition
Official title: Transfer of Healthy Gut Flora for Restoration of Intestinal Microbiota Via Enema (THRIVE) for Patients in the Rehabilitative Phase of Malnutrition: A Pilot Study Evaluating Microbial Engraftment, Safety and Nutritional Outcomes
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Severe Acute Malnutrition
Moderate Acute Malnutrition
Keywords: SAM
MAM
Lead sponsor: Microbiome Health Research Institute
Sponsor class: OTHER
Collaborators: name: University of Cape Town
First posted: 2017-03-22
Enrollment: 5
Sex: ALL
Minimum age (years): 12
Maximum age (years): 60
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.


Eligibility criteria: Participant Inclusion Criteria

Participants eligible to participate in this study must meet the following inclusion criteria:

1. Age 12 to 60 months.
2. 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
3. HIV negative
4. Received at last four weeks of optimal WHO treatment for malnutrition:

   1. Micronutrient supplementation (Vitamin A, zinc and iron) as recommended by local guidelines
   2. Nutritional rehabilitation as recommended by local guidelines.
5. Written informed consent obtained by parent or caregiver.

Participant Exclusion Criteria

Participants will not be able to participate if they meet any of the following exclusion criteria:

1. Evidence of current complicated malnutrition defined as any of the following:

   1. Admitted to acute care ward as inpatient
   2. Signs of severe acute infection such as pneumonia, bacteremia, meningitis. Minor infections such as candida dermatitis, pharyngitis, upper respiratory tract infections will be eligible for inclusion at the discretion of the study physician.
   3. One or more WHO Integrated Management of Childhood Illness danger signs.(3)
   4. Failure to pass appetite test.
   5. 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.
   6. Bilateral pitting pedal edema or generalized anasarca
2. 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.
3. 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.

   a. Fetal alcohol syndrome (FAS) is not an exclusion.
4. Presence of bilateral pitting edema Grade 2.
5. Contraindications to rectal catheter enema:

   1. Anorectal malformations
   2. Rectal prolapse
   3. Hirschsprungs disease
   4. Other contraindication to enema.
6. Primary immune deficiencies
7. Acute, persistent or chronic diarrhea.
8. Dysentery
9. Intestinal abnormalities including malformations, Hirschsprungs disease and short bowel syndrome
10. Any condition that the physician investigators deems unsafe, including other conditions or medications that the investigator determines puts the participant at greater risk from MTT

Primary outcomes:
measure: Serious Adverse Events
timeFrame: 56 days
Secondary outcomes:
measure: Nutritional recovery:
timeFrame: 56 days
measure: Clinical:
timeFrame: 56 days
measure: Microbiological:
timeFrame: 56 Days
measure: Translational:
timeFrame: 56 Days
Other outcomes:
Locations:
city: Cape Town
country: South Africa
facility: University of Cape Town
Study officials:
affiliation: Microbiome Health Research Institute
name: Majdi A Osman, MD MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Microbiome Health Research Institute
name: Shrish Budree, MD MBChB DCH FCPeds
role: PRINCIPAL_INVESTIGATOR
References: