Improving Cognition and Gestational Duration With Targeted Nutrition (COGENT)

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?

Study Overview

• Status: Active, not recruiting
• Conditions: Postpartum Depression; Preterm Birth; Child Development; Malnutrition in Pregnancy; Antepartum Depression
• Intervention / Treatment: 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; Dietary supplement: M-RUSF (Maternal Ready-to-Use Supplementary Food)

Detailed Description

Undernutrition in pregnancy is common, affecting nearly 10% of women worldwide and 25% of women in Sub-Saharan Africa, and increases risks for both mothers and their offspring, including bleeding, preterm birth, neonatal mortality, and impaired infant cognitive development. Available treatments have limited impact on these outcomes, which affect millions annually. A recent trial in Sierra Leone showed that pairing high-quality supplementary nutrition with anti-infective measures led to greater maternal weight gain, longer and heavier newborns, and reduced neonatal mortality. In addition, ante- and postpartum depression are underrecognized and undertreated in rural Sub-Saharan Africa.

The goal of this clinical trial is to test (1) a novel maternal ready-to-use supplementary food (M-RUSF+) and (2) a novel cognitive behavioral therapy (CBT) program developed for illiterate users, in undernourished pregnant women in Sierra Leone. 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?

Participants will present to government-run antenatal clinics for screening. If they quality for enrollment and consent to participate, they will undergo:

ANTENATALLY

• randomization to intervention vs. control group
• bi-weekly anthropometric measurements
• ultrasound gestational age estimation
• demographic, socioeconomic, and health history questionnaires
• bi-weekly blood pressure measurement
• bi-weekly screening for ante- and post-partum depression
• two blood spot collections

POSTNATALLY

• birth measurements of mother and offspring
• cord blood and placental sampling for a subset
• 5 clinic visits for mother and offspring anthropometric measurements, health history, breastfeeding practice, maternal mental health questions
• offspring developmental assessments

All participants will receive:

ANTENATALLY

• 100g/day of M-RUSF+ or M-RUSF, containing 530 Kcal, 19g protein, United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP) equivalent
• insecticide-treated bed nets
• a single dose of albendazole de-worming medicine
• monthly malaria chemoprophylaxis
• single doses of azithromycin in the second and third trimesters
• safe birth kits

If participants develop ante- or postpartum depression and are randomized to CBT, they will receive 6 sessions of CBT.

• Study Type: Interventional
• Enrollment (Actual): 1660
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sierra Leone
  • Southern Province
    • Bandajuma, Southern Province, Sierra Leone
      • Bandajuma
    • Bendu, Southern Province, Sierra Leone
      • Bendu Malen
    • Blama Massaquoi, Southern Province, Sierra Leone
      • Blama Massaquoi
    • Futa Peje, Southern Province, Sierra Leone
      • Futa Peje
    • Gbondapi, Southern Province, Sierra Leone
      • Gbondapi
    • Nyandehun, Southern Province, Sierra Leone
      • Nyandehun Malen
    • Potoru, Southern Province, Sierra Leone
      • Potoru
    • Pujehun, Southern Province, Sierra Leone
      • Pujehun Static
    • Sahn, Southern Province, Sierra Leone
      • Sahn Malen
    • Zimmi, Southern Province, Sierra Leone
      • Zimmi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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:

1. 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
2. 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
3. ≥ 13 years of age
4. Pregnant
5. 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:

1. 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
2. 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
3. Patient Health Questionnaire-9 score ≥ 9

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: M-RUSF+ (Maternal Ready-to-Use Supplementary Food + DHA/EPA/choline) and CBT; 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); Balanced energy protein supplement with added DHA/EPA/choline, micronutrients; Drug: Azithromycin; 1g dose; Drug: Albendazole; 400mg dose; Drug: Sulfadoxine pyrimethamine; Monthly, 1,500/75mg dose; Behavioral: Cognitive behavioral therapy; Novel program developed for illiterate end-users; Other: Insecticide-treated mosquito net; Bed net to prevent malaria
Experimental: M-RUSF+ (Maternal Ready-to-Use Supplementary Food + DHA/EPA/choline) and no CBT; 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); Balanced energy protein supplement with added DHA/EPA/choline, micronutrients; Drug: Azithromycin; 1g dose; Drug: Albendazole; 400mg dose; Drug: Sulfadoxine pyrimethamine; Monthly, 1,500/75mg dose; Other: Insecticide-treated mosquito net; Bed net to prevent malaria
Experimental: M-RUSF (Maternal Ready-to-use Supplementary Food without DHA/EPA/choline and CBT; 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.	Drug: Azithromycin; 1g dose; Drug: Albendazole; 400mg dose; Drug: Sulfadoxine pyrimethamine; Monthly, 1,500/75mg dose; Behavioral: Cognitive behavioral therapy; Novel program developed for illiterate end-users; Other: Insecticide-treated mosquito net; Bed net to prevent malaria; Dietary supplement: M-RUSF (Maternal Ready-to-Use Supplementary Food); Balanced energy protein supplement with added micronutrients
Experimental: M-RUSF (Maternal Ready-to-use Supplementary Food without DHA/EPA/choline and no CBT; 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.	Drug: Azithromycin; 1g dose; Drug: Albendazole; 400mg dose; Drug: Sulfadoxine pyrimethamine; Monthly, 1,500/75mg dose; Other: Insecticide-treated mosquito net; Bed net to prevent malaria; Dietary supplement: M-RUSF (Maternal Ready-to-Use Supplementary Food); Balanced energy protein supplement with added micronutrients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Malawi Developmental Assessment Tool (MDAT) global z-score	Infant global age-adjusted z-score on MDAT	9 months post-birth
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)
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early preterm birth	Birth < 34 weeks gestational age	Enrollment to 34 weeks' gestation
Birth weight	Infant weight at birth	Birth
Birth length	Infant length at birth	Birth
Low birth weight	Birth weight < 2.5 kg	Birth
Preterm birth	Birth < 37 weeks gestational age	Enrollment to 37 weeks' gestation
Neonatal mortality	Infant death within the first 28 days of life	Birth to 28 days of age
Infant mortality	Infant death	Birth to end of follow-up (9 months)
Birth chest circumference	Infant chest circumference	Birth
Birth thigh circumference	Infant thigh circumference	Birth
Birth head circumference	Infant head circumference	Birth
Infant weight at 6 weeks, 3 months, 6 months, 9 months	Infant weight	Birth to 9 months
Infant length at 6 weeks, 3 months, 6 months, 9 months	Infant length	Birth to 9 months
Infant length-for-age z-score at 6 weeks, 3 months, 6 months, 9 months	Infant length-for-age z-score	Birth to 9 months
Malawi Developmental Assessment Test sub-domain z-scores	Gross motor, fine motor, language, and social domain z-scores (expected range -4 to 2, higher scores are better)	9 months after birth
Depressive symptoms	Adapted Patient Health Questionnaire-9 score (range 0-27, higher scores are worse)	Through study completion, an average of 1.25 years
Maternal and infant choline status	Blood choline concentration	From Enrollment to delivery, an average of 15 weeks
Maternal weight gain	Average weekly weight gain	From Enrollment to delivery, an average of 15 weeks
Post-term delivery	Delivery > 42 weeks' gestation	From Enrollment to delivery, an average of 15 weeks
Depression incidence	Adapted PHQ-9 >= 9	8 weeks from time of depression diagnosis
Gestational duration	Enrollment ultrasound estimated gestational age plus time between enrollment and delivery. For this secondary outcome, all enrolled women will be included in analysis.	From Enrollment to birth, an average of 15 weeks
Maternal and infant DHA status	Maternal plasma, cord blood DHA status	From Enrollment to delivery, an average of 15 weeks
Placental weight	Weight of placenta in grams	Birth
Small for gestational age (SGA)	Under 10th percentile in birth weight for gestational age	Birth

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intrauterine growth parameters	Estimated weight, head circumference, femur length, placental size	Subset of participants (enrollment GA <= 24 weeks) to undergo q4-6week serial ultrasounds
Gestational duration by baseline DHA status	Gestational duration modeled by enrollment DHA % of plasma fatty acids	From enrollment to birth, an average of 15 weeks
Gestational duration by baseline maternal MUAC	Gestational duration modeled by enrollment MUAC	From enrollment to birth, an average of 15 weeks
Gestational duration by enrollment gestational age	Gestational duration modeled by enrollment GA	From enrollment to birth, an average of 15 weeks
Gestational duration by enrollment maternal age	Gestational duration modeled by enrollment maternal age	From enrollment to birth, an average of 15 weeks
Gestational duration by maternal parity	Gestational duration compared across levels of maternal parity	From enrollment to birth, an average of 15 weeks

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: United States Department of Agriculture (USDA); Project Peanut Butter; Ministry of Health and Sanitation, Sierra Leone; Open Philanthropy
• Investigators: Principal Investigator: Mark J Manary, MD, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: June 29, 2023
• First Submitted That Met QC Criteria: July 14, 2023
• First Posted (Actual): July 17, 2023

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 26, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Mental Disorders; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Mood Disorders; Puerperal Disorders; Depressive Disorder; Premature Birth; Depression, Postpartum; Organic Chemicals; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Acids, Acyclic; Carboxylic Acids; Equipment and Supplies; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Macrolides; Lactones; Protective Devices; Erythromycin; Polyketides; Carbamates; Mosquito Nets; Azithromycin; Albendazole; Cognitive Behavioral Therapy; fanasil, pyrimethamine drug combination; Insecticide-Treated Bednets
• Other Study ID Numbers: 202305139

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All collected Individual; Patient Data (IPD).
• IPD Sharing Time Frame: Within 12 months of primary publication
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No