Choline to Prevent SAM in Children With MAM

NCT ID: NCT06214897

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

1500 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-03-18

Study Completion Date

2026-06-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The goal of this clinical trial is to test choline supplementation in children with moderate acute malnutrition in Malawi. The main question it aims to answer is:

Will provision of RUSF with added choline (500mg/day) throughout treatment of moderate acute malnutrition (up to 12 weeks) reduce deterioration to severe acute malnutrition among 6-59 month old Malawian children compared with standard RUSF?

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Moderate acute malnutrition (MAM) is common among children worldwide, with a prevalence of 50M and an annual incidence likely 3-5x this number. It is defined by mid-upper arm circumference (MUAC) ≥ 11.5 cm and \< 12.5 cm or weight-for-length (WLZ) z-score ≥ -3 and \< -2. MAM increases a child's risk of deterioration to severe acute malnutrition (SAM), stunting, death, infectious illnesses, and impaired cognitive development. In Malawi, in the year following MAM treatment, nearly one-third of children will face a repeat episode of MAM, 7-10% will develop SAM, and 4% will die. There is much progress yet to be made toward improving rates of recovery and preventing the worst outcomes for the millions of children suffering from MAM each year.

One potential avenue for improving outcomes in MAM is modification of supplementary foods used for its treatment. Choline is an essential nutrient for human health and development, evidence for which is largely drawn from animal models of choline deficiency in which various somatic and cognitive developmental abnormalities are found. Of the trials that have evaluated choline supplementation in humans, many have focused on the role of choline in brain development and, specifically, how it may help foster improved cognitive development in the setting of various insults, such as fetal alcohol syndrome.

There is also a growing body of evidence describing the many roles choline plays outside of the brain, including in the etiology of malnutrition. Recently, choline deficiency has been implicated in the development of kwashiorkor, an enigmatic form of severe acute malnutrition characterized by pitting edema, dermatitis, hair color changes, and fatty liver disease with inflammation. Animal models of choline deficiency display a remarkably similar phenotype to kwashiorkor. When choline has been given to mice, rats, and dogs with kwashiorkor-like malnutrition, the hallmark features of the disease have resolved. This line of evidence suggests a causal role for choline deficiency in kwashiorkor, proposed mechanisms for which include choline's functions in 1-carbon metabolism, sulfur amino acid recycling, and sparing of the essential amino acid methionine. Methionine is the key deficient amino acid in maize-predominant diets, such as are consumed in Malawi. Choline is most abundant in animal-source foods, precisely those which are lacking in the diets of many rural Malawian children. Kwashiorkor accounts for more than one-third of SAM in Malawi in children under 5 years of age and 80% of MAM deterioration to SAM. If the addition of choline to supplementary foods were demonstrated to reduce deterioration to SAM among children with MAM and thereby promote recovery, this would represent an important advance in MAM treatment.

Despite the data supporting choline's essential role in human health and emerging data on its potential therapeutic role in malnutrition, there are no specifications for choline content in food aid products. Common MAM treatment options, such as corn-soy-blend plus and RUSF contain 50-70mg choline, approximately one-third of the 150-200mg recommended for well children 6mo-3y of age. This does not account for the likely increased demand for choline in the setting of malnutrition.

This will be an individually randomized, investigator-blinded, controlled clinical trial. This trial will be conducted at 10 rural sites in southern Malawi where the co-Principal Investigator, Mark Manary, has run malnutrition treatment clinics for over 15 years. The study will include 1500 children (750 per group) 6-59 months of age with uncomplicated MAM, as defined by mid-upper arm circumference (MUAC) ≥ 11.5 cm and \< 12.5 cm and/or weight-for-length z-score (WLZ) ≥ -3 and \< -2. Exclusion criteria will be presence of nutritional edema, features of complicated MAM, such as mental status changes or breathing issues, as well as participation in a separate feeding program, known allergy to study food ingredient, intention to move away from catchment area within 3 months, developmental delay, or presence of a chronic severe medical condition such as congenital heart disease. Those who wish to take part will undergo randomization, wherein they will remove a single small opaque envelope from a larger opaque envelope and open it, revealing a colored sticker that will correspond to their study group. Caregivers will receive nutrition counselling, complete questionnaires pertaining to demographic, health history/symptoms, and socioeconomic information, and be provided with a two-week supply of their allotted study food for their child. Participants will receive approximately 500 Kcal/day of either C-RUSF or RUSF until they reach a clinical outcome (i.e., graduate, deteriorate to SAM, fail/remain MAM, transfer to hospital, death, default) or for a maximum of 12 weeks. They will be asked to return to clinic fortnightly for re-assessment of anthropometry, illness symptoms, and re-provision of supplementary food until they reach a study outcome. Participants will undergo MDAT testing at time of MAM outcome as well as 5-7 months after MAM outcome to undergo repeat MDAT testing. A randomly chosen subset of participants will undergo blood spot collection at time of MAM outcome.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Moderate Acute Malnutrition

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Investigators Outcome Assessors
The intervention and control sachets of RUSF will be packaged such that investigators, outcomes assessors, and participants/caregivers will not know their identity.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

C-RUSF (Ready-to-use Supplemental Food with added choline)

A daily dose of 500 Kcal of RUSF containing 500mg choline will be provided

Group Type EXPERIMENTAL

C-RUSF (Ready-to-use Supplemental Food with added Choline)

Intervention Type DIETARY_SUPPLEMENT

Ready-to-use Supplemental Food with added Choline

S-RUSF (Standard Ready-to-use Supplemental Food without added choline)

A daily dose of 500 Kcal of RUSF without choline

Group Type ACTIVE_COMPARATOR

S-RUSF (Ready-to-use Supplemental Food without added Choline)

Intervention Type DIETARY_SUPPLEMENT

Standard Ready-to-use Supplemental Food

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

C-RUSF (Ready-to-use Supplemental Food with added Choline)

Ready-to-use Supplemental Food with added Choline

Intervention Type DIETARY_SUPPLEMENT

S-RUSF (Ready-to-use Supplemental Food without added Choline)

Standard Ready-to-use Supplemental Food

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 6-59 months of age
* uncomplicated MAM (mid-upper arm circumference (MUAC) ≥ 11.5 cm and \< 12.5 cm and/or weight-for-length z-score (WLZ) ≥ -3 and \< -2)
* availability for the duration of the study with no plan to move from the catchment area of a participating clinic

Exclusion Criteria

* presence of nutritional edema
* features of complicated MAM, such as mental status changes or breathing issues
* participation in another feeding program
* known allergy to study food ingredient
* intention to move away from catchment area within 9 months
* developmental delay
* presence of a chronic severe medical condition (other than TB or HIV) such as congenital heart disease
Minimum Eligible Age

6 Months

Maximum Eligible Age

59 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Project Peanut Butter

OTHER

Sponsor Role collaborator

Kamuzu University of Health Sciences

OTHER

Sponsor Role collaborator

Balchem Corp

INDUSTRY

Sponsor Role collaborator

Washington University School of Medicine

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Mark J Manary, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Chikonde Health Center

Chikonde, , Malawi

Site Status

Chipolonga Health Center

Chipolonga, , Malawi

Site Status

Makhwira Health Center

Makhwira, , Malawi

Site Status

Mbiza Health Clinic

Mbiza, , Malawi

Site Status

Milonde Health Center

Milonde, , Malawi

Site Status

Mitondo Health Center

Mitondo, , Malawi

Site Status

Muloza Health Clinic

Muloza, , Malawi

Site Status

Namasalima Health Center

Namasalima, , Malawi

Site Status

Naphimba Health Center

Naphimba, , Malawi

Site Status

Nkhate Health Clinic

Nkhate, , Malawi

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Malawi

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

202308159

Identifier Type: -

Identifier Source: org_study_id