Improving Cognition and Gestational Duration With Targeted Nutrition

NCT05949190 | Active Not Recruiting

• 1 other identifier: 202305139
• Study Type: interventional
• Target: 1,660
• Locations: 1 country
• Sites: 10

Brief Summary

The goal of this clinical trial is to test (1) a novel maternal ready-to-use supplementary food and (2) a novel cognitive behavioral therapy intervention in undernourished Sierra Leonean women. The main questions it aims to answer are:

• Will the addition of omega-3 long-chain polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), as well as choline, to a maternal ready-to-use supplementary food (M-RUSF+) prolong gestation when compared with a similar supplementary food except that it lacks DHA, EPA, and choline (M-RUSF)?
• Will M-RUSF+ improve infant cognitive development at 9 months of age when compared with M-RUSF?
• Will the novel CBT program improve ante- and post-partum depression?

Conditions

Malnutrition in Pregnancy; Preterm Birth; Child Development; Postpartum Depression; Antepartum Depression

Outcome Measures

Primary Outcomes (3)

• Gestational duration

  Enrollment ultrasound estimated gestational age plus time between enrollment and delivery. For the primary outcome, this will only be assessed among participants enrolled \<= 30 weeks gestational age and with singleton live births

  Enrollment to birth (range 2 to 26 weeks)

• Malawi Developmental Assessment Tool (MDAT) global z-score

  Infant global age-adjusted z-score on MDAT

  9 months post-birth

• Adapted Patient Health Questionnaire-9 (PHQ-9) score

  Among participants who develop ante- or post-partum depression, adapted Patient Health Questionnaire-9 score, (range 0-27, higher scores are worse)

  8 weeks after diagnosis with ante- or post-partum depression

Secondary Outcomes (23)

• Early preterm birth

  Enrollment to 34 weeks' gestation

• Birth weight

  Birth

• Birth length

  Birth

• Low birth weight

  Birth

• Malawi Developmental Assessment Test sub-domain z-scores

  9 months after birth

Other Outcomes (6)

• Intrauterine growth parameters

  Subset of participants (enrollment GA <= 24 weeks) to undergo q4-6week serial ultrasounds

• Gestational duration by baseline DHA status

  From enrollment to birth, an average of 15 weeks

• Gestational duration by baseline maternal MUAC

  From enrollment to birth, an average of 15 weeks

Study Arms (4)

M-RUSF+ (Maternal Ready-to-Use Supplementary Food + DHA/EPA/choline) and CBT

EXPERIMENTAL

Factorial 1. A daily dose of 500mg DHA, 500mg EPA, and 550mg choline will be added to the maternal balanced energy-protein RUSF. One sachet (daily dose) will provide 520 Kcal, 18g protein, and the same quantities of micronutrients as the United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP) for women. M-RUSF+ will be vacuum sealed and packaged in foil sachets containing 100g of food. Factorial 2. Among participants randomized to receive M-RUSF+ vs. M-RUSF, those who develop ante- or postpartum depression will receive 6 sessions of CBT adopted for use in illiterate populations will be provided.

Dietary Supplement: M-RUSF+ (Maternal Ready-to-Use Supplementary Food + DHA/EPA/choline); Drug: Azithromycin; Drug: Albendazole; Drug: Sulfadoxine pyrimethamine; Behavioral: Cognitive behavioral therapy; Other: Insecticide-treated mosquito net

M-RUSF+ (Maternal Ready-to-Use Supplementary Food + DHA/EPA/choline) and no CBT

EXPERIMENTAL

Factorial 1. A daily dose of 500mg DHA, 500mg EPA, and 550mg choline will be added to the maternal balanced energy-protein RUSF. One sachet (daily dose) will provide 520 Kcal, 18g protein, and the same quantities of micronutrients as the UNICEF/World Health Organization/United Nations multiple micronutrient supplement for pregnant/lactating women. M-RUSF+ will be vacuum sealed and packaged in foil sachets containing 100g of food. Factorial 2. Participants who develop ante- or postpartum depression will not receive CBT.

Dietary Supplement: M-RUSF+ (Maternal Ready-to-Use Supplementary Food + DHA/EPA/choline); Drug: Azithromycin; Drug: Albendazole; Drug: Sulfadoxine pyrimethamine; Other: Insecticide-treated mosquito net

M-RUSF (Maternal Ready-to-use Supplementary Food without DHA/EPA/choline and CBT

EXPERIMENTAL

Factorial 1. M-RUSF will be similar to M-RUSF+, except it will not contain added DHA or EPA, and will only contain 5mg of added choline to help with flavor masking. One sachet (daily dose) will provide 520 Kcal, 18g protein, and the same quantities of micronutrients as the UNIMMAP for pregnant/lactating women. M-RUSF+ will be vacuum sealed and packaged in foil sachets containing 100g of food. Factorial 2. Participants who develop ante- or postpartum depression will receive 6 sessions of CBT adopted for use in illiterate populations will be provided.

Dietary Supplement: M-RUSF (Maternal Ready-to-Use Supplementary Food); Drug: Azithromycin; Drug: Albendazole; Drug: Sulfadoxine pyrimethamine; Behavioral: Cognitive behavioral therapy; Other: Insecticide-treated mosquito net

M-RUSF (Maternal Ready-to-use Supplementary Food without DHA/EPA/choline and no CBT

EXPERIMENTAL

Factorial 1. M-RUSF will be similar to M-RUSF+, except it will not contain added DHA or EPA, and will only contain 5mg of added choline to help with flavor masking. One sachet (daily dose) will provide 520 Kcal, 18g protein, and the same quantities of micronutrients as the UNIMMAP for pregnant/lactating women. M-RUSF+ will be vacuum sealed and packaged in foil sachets containing 100g of food. Factorial 2. Participants who develop ante- or postpartum depression will not receive CBT.

Dietary Supplement: M-RUSF (Maternal Ready-to-Use Supplementary Food); Drug: Azithromycin; Drug: Albendazole; Drug: Sulfadoxine pyrimethamine; Other: Insecticide-treated mosquito net

Interventions

Azithromycin DRUG

1g dose

M-RUSF (Maternal Ready-to-use Supplementary Food without DHA/EPA/choline and CBT; M-RUSF (Maternal Ready-to-use Supplementary Food without DHA/EPA/choline and no CBT; M-RUSF+ (Maternal Ready-to-Use Supplementary Food + DHA/EPA/choline) and CBT; M-RUSF+ (Maternal Ready-to-Use Supplementary Food + DHA/EPA/choline) and no CBT

Albendazole DRUG

400mg dose

M-RUSF (Maternal Ready-to-use Supplementary Food without DHA/EPA/choline and CBT; M-RUSF (Maternal Ready-to-use Supplementary Food without DHA/EPA/choline and no CBT; M-RUSF+ (Maternal Ready-to-Use Supplementary Food + DHA/EPA/choline) and CBT; M-RUSF+ (Maternal Ready-to-Use Supplementary Food + DHA/EPA/choline) and no CBT

Sulfadoxine pyrimethamine DRUG

Monthly, 1,500/75mg dose

M-RUSF (Maternal Ready-to-use Supplementary Food without DHA/EPA/choline and CBT; M-RUSF (Maternal Ready-to-use Supplementary Food without DHA/EPA/choline and no CBT; M-RUSF+ (Maternal Ready-to-Use Supplementary Food + DHA/EPA/choline) and CBT; M-RUSF+ (Maternal Ready-to-Use Supplementary Food + DHA/EPA/choline) and no CBT

Cognitive behavioral therapy BEHAVIORAL

Novel program developed for illiterate end-users

M-RUSF (Maternal Ready-to-use Supplementary Food without DHA/EPA/choline and CBT; M-RUSF+ (Maternal Ready-to-Use Supplementary Food + DHA/EPA/choline) and CBT

Insecticide-treated mosquito net OTHER

Bed net to prevent malaria

M-RUSF (Maternal Ready-to-use Supplementary Food without DHA/EPA/choline and CBT; M-RUSF (Maternal Ready-to-use Supplementary Food without DHA/EPA/choline and no CBT; M-RUSF+ (Maternal Ready-to-Use Supplementary Food + DHA/EPA/choline) and CBT; M-RUSF+ (Maternal Ready-to-Use Supplementary Food + DHA/EPA/choline) and no CBT

M-RUSF (Maternal Ready-to-Use Supplementary Food) DIETARY_SUPPLEMENT

Balanced energy protein supplement with added micronutrients

M-RUSF (Maternal Ready-to-use Supplementary Food without DHA/EPA/choline and CBT; M-RUSF (Maternal Ready-to-use Supplementary Food without DHA/EPA/choline and no CBT

M-RUSF+ (Maternal Ready-to-Use Supplementary Food + DHA/EPA/choline) DIETARY_SUPPLEMENT

Balanced energy protein supplement with added DHA/EPA/choline, micronutrients

M-RUSF+ (Maternal Ready-to-Use Supplementary Food + DHA/EPA/choline) and CBT; M-RUSF+ (Maternal Ready-to-Use Supplementary Food + DHA/EPA/choline) and no CBT

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible to participate in the M-RUSF+ vs. M-RUSF element of the study, an individual must meet all of the following criteria:
• Provision of signed (or thumb-printed) and dated informed consent form 1a. Women who are ≥ 18 years of age or married will be allowed to consent for themselves 1b. Women who are \< 18 years of age and unmarried must provide assent and a parent or guardian must provide consent
• Stated willingness to comply with all study procedures and availability for the duration of the study, including no plan to move from the catchment area of a participating clinic
• ≥ 13 years of age
• Pregnant
• Mid-upper arm circumference ≤ 23 cm or body-mass index \< 18.5
• In order to be eligible to participate in the CBT vs. no CBT element of the study (factorial design with the above), an individual must be enrolled in the M-RUSF+ vs. M-RUSF study and meet the following criteria:
• Provision of signed (or thumb-printed) and dated informed consent form 1a. Women who are ≥ 18 years of age or married will be allowed to consent for themselves 1b. Women who are \< 18 years of age and unmarried must assent and a parent or guardian consent must provide consent
• Stated willingness to comply with all study procedures and availability for the duration of the study, including no plan to move from the catchment area of a participating clinic
• Patient Health Questionnaire-9 score ≥ 9

You may not qualify if:

• Participation in a concomitant supplementary feeding program
• Known allergy to components of intervention or control study food or medications
• Known gestational diabetes
• Hypertension
• Severe anemia, or other condition requiring immediate hospitalization

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Project Peanut Butter: collaborator
• Open Philanthropy: collaborator
• United States Department of Agriculture (USDA): collaborator
• Ministry of Health and Sanitation, Sierra Leone: collaborator

Study Sites (10)

Bandajuma

Bandajuma, Southern Province, Sierra Leone

Location

Bendu Malen

Bendu, Southern Province, Sierra Leone

Location

Blama Massaquoi

Blama Massaquoi, Southern Province, Sierra Leone

Location

Futa Peje

Futa Peje, Southern Province, Sierra Leone

Location

Gbondapi

Gbondapi, Southern Province, Sierra Leone

Location

Nyandehun Malen

Nyandehun, Southern Province, Sierra Leone

Location

Potoru

Potoru, Southern Province, Sierra Leone

Location

Pujehun Static

Pujehun, Southern Province, Sierra Leone

Location

Sahn Malen

Sahn, Southern Province, Sierra Leone

Location

Zimmi

Zimmi, Southern Province, Sierra Leone

Location

MeSH Terms

Conditions

Premature Birth; Depression, Postpartum

Interventions

Azithromycin; Albendazole; fanasil, pyrimethamine drug combination; Cognitive Behavioral Therapy; Insecticide-Treated Bednets

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Puerperal Disorders; Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Mosquito Nets; Protective Devices; Equipment and Supplies

Study Officials

• Mark J Manary, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: In the food comparison, while the 2 study foods taste similar, full masking cannot be guaranteed. In the CBT comparison, participants and therapists will not be masked. In all cases, outcomes assessors will be masked.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 2x2 factorial design

Study Record Dates

• First Submitted: June 29, 2023
• First Posted: July 17, 2023
• Study Start: August 18, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: March 2, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Within 12 months of primary publication

Locations

SI (10)