Severe Acute MalnutritionPhase 1THRIVENCT03087097
Transfer of Healthy Gut Flora for Restoration of Intestinal Microbiota Via Enema for Patients in the Rehabilitative Phase of Malnutrition
A Phase 1 study testing Fecal Microbiota Transplantation in people with Severe Acute Malnutrition and Moderate Acute Malnutrition, run by Microbiome Health Research Institute at 1 site in South Africa.
Trial 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… Read more about this study
- Who is it for?
- Ages 12 to 60 months
- Conditions the study is for
- Severe Acute Malnutrition, Moderate Acute Malnutrition
- What is being tested?
- Fecal Microbiota Transplantation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteSouth Africa
- Study dates
- 11 Apr 2019to 21 Jul 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 60 months
- All sexes
- No healthy volunteers
- Child
Participant Inclusion Criteria
Participants eligible to participate in this study must meet the following inclusion criteria:
- 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 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.
Participant Exclusion Criteria
Participants will not be able to participate if they meet any of the following exclusion criteria:
- Evidence of current complicated malnutrition defined as any of the following:
- Admitted to acute care ward as inpatient
- 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.
- 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.
- Fetal alcohol syndrome (FAS) is not an exclusion.
- 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
- Acute, persistent or chronic diarrhea.
- Dysentery
- Intestinal abnormalities including malformations, Hirschsprungs disease and short bowel syndrome
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
- Being tested
- Fecal Microbiota Transplantation
- Keywords
- SAM, MAM
- Medical subject headings
- Severe Acute Malnutrition
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fecal Microbiota TransplantationBiological
Also called Microbiota transfer therapy (MTT)
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.
| Study group | Role | What they receive |
|---|---|---|
| Fecal Microbiota Transplant | Experimental | FMT by enema: 10mL/kg (maximum 150mL) of healthy donor human intestinal microbiota will be infused. Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serious Adverse Events
Number of participants with an Adverse Event grade 2 or above up to 56 days post-treatment
Measured: 56 days
Secondary outcomes (4)
Nutritional recovery:
Proportion of participants with nutritional recovery at day 56 after randomization. Defined as weight for height z-score (WHZ) ≥ -2 or MUAC ≥ 125 mm. In cases where there is a significant discrepancy between the weight and MUAC the participants weight will be used as the definitive measure.
Measured: 56 days
Clinical:
Presence of signs and symptoms or complications of acute malnutrition. Clinical signs include fever (axillary temperature > 38.5⁰C), tachypnea (average of two measures; defined as respiratory rate of > 40 breaths per minute for children 12-60 months of age). Symptoms include diarrhea (≥ 3 loose stools in the last 24 hours), vomiting, and cough.
Measured: 56 days
Microbiological:
Assess engraftment of donor microbial communities in recipients through taxonomic characterization of donor and recipient microbiota pre- and post-MTT using both 16S rRNA and metagenomic techniques.
Measured: 56 Days
Translational:
Assess the capacity for MTT to normalize biomarkers correlated with disease status and mortality in malnutrition. Stool biomarkers include Myeloperoxidase, Alpha-1-Antitrypsin, fecal calprotectin and neopterin. Serological biomarkers include CRP, endotoxin assay (Hek-Blue), and leptin.
Measured: 56 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2017
- Study start11 Apr 2019
- Primary completion21 Jul 2020
- Study completion21 Jul 2020
Why it stopped: COVID-19 pandemic and resource constraints
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe Acute MalnutritionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Microbiome Health Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- University of Cape Town
- Responsible party
- Sponsor
- Investigators
- Majdi A Osman, MD MPH, Principal investigator, Microbiome Health Research InstituteShrish Budree, MD MBChB DCH FCPeds, Principal investigator, Microbiome Health Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03087097
- Sponsor's protocol ID
- THRIVE001
- Acronym
- THRIVE
- Status last verified
- Jan 2021
- First submitted
- 12 Dec 2016
- Last updated
- 13 Jan 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03087097
- Acronym / sponsor ID
- THRIVE / THRIVE001
- Keywords
- SAM, MAM
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: COVID-19 pandemic and resource constraints
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Microbiome Health Research InstituteUniversity, hospital or other
- Collaborators
- University of Cape Town
- Study start
- 11 Apr 2019 (actual)
- Primary completion
- 21 Jul 2020 (actual)
- Study completion
- 21 Jul 2020 (actual)
- First posted
- 22 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fecal Microbiota Transplant | Experimental | Biological: Fecal Microbiota TransplantationFMT by enema: 10mL/kg (maximum 150mL) of healthy donor human intestinal microbiota will be infused. |
| Standard of Care | No intervention | –Standard of care treatment for malnutrition as prescribed by local and national Department of Health Guidelines |
Who may qualify
- Ages
- 12 to 60 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fecal Microbiota TransplantationAlso: Microbiota transfer therapy (MTT)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. | Biological | Fecal Microbiota Transplant |
Primary outcome
Serious Adverse Events
Time frame: 56 days
Number of participants with an Adverse Event grade 2 or above up to 56 days post-treatment
4 secondary outcomes
Nutritional recovery:
Time frame: 56 days
Clinical:
Time frame: 56 days
Microbiological:
Time frame: 56 Days
Translational:
Time frame: 56 Days
Results and safety
The study was stopped early (reason given: COVID-19 pandemic and resource constraints). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2021.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Majdi A Osman, MD MPH principal investigator
Microbiome Health Research Institute
Shrish Budree, MD MBChB DCH FCPeds principal investigator
Microbiome Health Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fecal Microbiota Transplantation in people with Severe Acute Malnutrition and Moderate Acute Malnutrition, run by Microbiome Health Research Institute at 1 site in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: COVID-19 pandemic and resource constraints). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serious Adverse Events (time frame: 56 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2021.