COGENT: Improving Cognition and Gestational Duration With Targeted Nutrition

Sponsor

Washington University School of Medicine (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05949190

Collaborator

Project Peanut Butter (Other), Open Philanthropy (Other), United States Department of Agriculture (USDA) (U.S. Fed), Ministry of Health and Sanitation, Sierra Leone (Other)

1,600

Enrollment

Arms

31.1

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Undernutrition in pregnancy 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. 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
bi-weekly anthropometric measurements
ultrasound gestational age
demographic, socioeconomic, and health history questionnaires
bi-weekly screening for ante- and post-partum depression
two blood spot collections

POSTNATALLY

birth measurements of mother and offspring
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
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.

Condition or Disease	Intervention/Treatment	Phase
Malnutrition in Pregnancy Preterm Birth Child Development Postpartum Depression Antepartum Depression	Dietary Supplement: M-RUSF+ (Maternal Ready-to-Use Supplementary Food + DHA/EPA/choline) 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	N/A

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.

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 Design

Study Type:

Interventional

Anticipated Enrollment :

1600 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Intervention Model Description:

2x2 factorial design2x2 factorial design

Masking:

Triple (Care Provider, Investigator, Outcomes Assessor)

Masking Description:

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.

Primary Purpose:

Treatment

Official Title:

Improving Cognition and Gestational Duration With Targeted Nutrition

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Feb 1, 2026

Anticipated Study Completion Date :

Feb 1, 2026

Arms and Interventions

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.	Dietary Supplement: M-RUSF (Maternal Ready-to-Use Supplementary Food) Balanced energy protein supplement with added 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 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.	Dietary Supplement: M-RUSF (Maternal Ready-to-Use Supplementary Food) Balanced energy protein supplement with added 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

Outcome Measures

Primary Outcome Measures

Gestational duration [Enrollment to birth 2 to 26 weeks]
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
Malawi Developmental Assessment Tool (MDAT) global z-score [9 months post-birth]
Infant global age-adjusted z-score on MDAT
Adapted Patient Health Questionnaire-9 (PHQ-9) score [8 weeks after diagnosis with ante- or post-partum depression]
Among participants who develop ante- or post-partum depression, adapted Patient Health Questionnaire-9 score, range 0-27 higher scores are worse

Secondary Outcome Measures

Early preterm birth [Enrollment to 34 weeks' gestation]
Birth < 34 weeks gestational age
Birth weight [Birth]
Infant weight at birth
Birth length [Birth]
Infant length at birth
Low birth weight [Birth]
Birth weight < 2.5 kg
Malawi Developmental Assessment Test sub-domain z-scores [9 months after birth]
Gross motor, fine motor, language, and social domain z-scores range -4 to 2 higher scores are better
Preterm birth [Enrollment to 37 weeks' gestation]
Birth < 37 weeks gestational age
Neonatal mortality [Birth to 28 days of age]
Infant death within the first 28 days of life
Infant mortality [Birth to end of follow-up (9 months)]
Infant death
Depressive symptoms [through study completion, and average of 1.25 years]
Patient Health Questionnaire-9 score range 0-27 higher scores are worse
Maternal and infant DHA status [from Enrollment to delivery, an average of 15 weeks]
Plasma, Red Blood Cell (RBC) membrane DHA status
Maternal and infant choline status [from Enrollment to delivery, an average of 15 weeks]
Blood choline concentration
Maternal weight gain [from Enrollment to delivery, an average of 15 weeks]
Average weekly weight gain
Post-term delivery [from Enrollment to delivery, and average of 15 weeks]
Delivery > 42 weeks' gestation
Depression incidence [16 weeks from time of depression diagnosis]
PHQ-9 >= 9
Birth chest circumference [Birth]
Infant chest circumference
Birth thigh circumference [Birth]
Infant thigh circumference
Birth head circumference [Birth]
Infant head circumference
Infant weight at 6 weeks, 3 months, 6 months, 9 months [Birth to 9 months]
Infant weight
Infant length at 6 weeks, 3 months, 6 months, 9 months [Birth to 9 months]
Infant length
Infant length-for-age z-score at 6 weeks, 3 months, 6 months, 9 months [Birth to 9 months]
Infant length-for-age z-score
Gestational duration [from Enrollment to birth, an average of 15 weeks]
Enrollment ultrasound estimated gestational age plus time between enrollment and delivery. For this secondary outcome, all enrolled women will be included in analysis.

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

Provision of signed (or thumb-printed) and dated informed consent form 1a. Women ≥ 16 years of age will be allowed to consent for themselves 1b. Women < 16 years of age 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 ≥ 16 years of age will be allowed to consent for themselves 1b. Women < 16 years of age 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

Exclusion Criteria:

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