Improving Cognition and Gestational Duration With Targeted Nutrition

Preterm Birth Clinical Trial

— COGENT  

Official title:

Improving Cognition and Gestational Duration With Targeted Nutrition

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05949190
• Other study ID #: 202305139
• Status: Recruiting
• Phase: N/A
• Start date: August 18, 2023
• Est. completion date: February 2026

Study information

• Verified date: March 2024
• Source: Washington University School of Medicine
• Contact: Mark J Manary, MD
• Phone: +1 314-454-2341
• Email: manarymj[@]wustl.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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?

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1600
• Est. completion date: February 2026
• Est. primary completion date: February 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Antepartum Depression
• Child Development
• Depression
• Depression, Postpartum
• Depressive Disorder
• Malnutrition
• Malnutrition in Pregnancy
• Postpartum Depression
• Premature Birth
• Preterm Birth

Intervention

Dietary Supplement:
• M-RUSF+ (Maternal Ready-to-Use Supplementary Food + DHA/EPA/choline)
Balanced energy protein supplement with added DHA/EPA/choline, micronutrients
• M-RUSF (Maternal Ready-to-Use Supplementary Food)
Balanced energy protein supplement with added micronutrients

Drug:
• Azithromycin
1g dose
• Albendazole
400mg dose
• 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

Locations

Country	Name	City	State
Sierra Leone	Bandajuma	Bandajuma	Southern
Sierra Leone	Bendu Malen	Bendu	Southern
Sierra Leone	Blama Massaquoi	Blama Massaquoi	Southern
Sierra Leone	Futa Peje	Futa Peje	Southern
Sierra Leone	Gbondapi	Gbondapi	Southern
Sierra Leone	Nyandehun Malen	Nyandehun	Southern
Sierra Leone	Potoru	Potoru	Southern
Sierra Leone	Pujehun Static	Pujehun	Southern
Sierra Leone	Sahn Malen	Sahn	Southern
Sierra Leone	Zimmi	Zimmi	Southern

Sponsors (5)

Lead Sponsor	Collaborator
Washington University School of Medicine	Ministry of Health and Sanitation, Sierra Leone, Open Philanthropy, Project Peanut Butter, United States Department of Agriculture (USDA)

Country where clinical trial is conducted

Sierra Leone, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Intrauterine growth parameters	Estimated weight, head circumference, femur length, placental size	Subset of participants (enrollment GA <= 24 weeks) to undergo q4-6week serial ultrasounds
Other	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
Other	Gestational duration by baseline maternal MUAC	Gestational duration modeled by enrollment MUAC	From enrollment to birth, an average of 15 weeks
Other	Gestational duration by enrollment gestational age	Gestational duration modeled by enrollment GA	From enrollment to birth, an average of 15 weeks
Other	Gestational duration by enrollment maternal age	Gestational duration modeled by enrollment maternal age	From enrollment to birth, an average of 15 weeks
Other	Gestational duration by maternal parity	Gestational duration compared across levels of maternal parity	From enrollment to birth, an average of 15 weeks
Primary	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)
Primary	Malawi Developmental Assessment Tool (MDAT) global z-score	Infant global age-adjusted z-score on MDAT	9 months post-birth
Primary	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	Early preterm birth	Birth < 34 weeks gestational age	Enrollment to 34 weeks' gestation
Secondary	Birth weight	Infant weight at birth	Birth
Secondary	Birth length	Infant length at birth	Birth
Secondary	Low birth weight	Birth weight < 2.5 kg	Birth
Secondary	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
Secondary	Preterm birth	Birth < 37 weeks gestational age	Enrollment to 37 weeks' gestation
Secondary	Neonatal mortality	Infant death within the first 28 days of life	Birth to 28 days of age
Secondary	Infant mortality	Infant death	Birth to end of follow-up (9 months)
Secondary	Depressive symptoms	Adapted Patient Health Questionnaire-9 score (range 0-27, higher scores are worse)	Through study completion, an average of 1.25 years
Secondary	Maternal and infant DHA status	Maternal plasma, cord blood DHA status	From Enrollment to delivery, an average of 15 weeks
Secondary	Maternal and infant choline status	Blood choline concentration	From Enrollment to delivery, an average of 15 weeks
Secondary	Maternal weight gain	Average weekly weight gain	From Enrollment to delivery, an average of 15 weeks
Secondary	Post-term delivery	Delivery > 42 weeks' gestation	From Enrollment to delivery, an average of 15 weeks
Secondary	Depression incidence	Adapted PHQ-9 >= 9	8 weeks from time of depression diagnosis
Secondary	Birth chest circumference	Infant chest circumference	Birth
Secondary	Birth thigh circumference	Infant thigh circumference	Birth
Secondary	Birth head circumference	Infant head circumference	Birth
Secondary	Infant weight at 6 weeks, 3 months, 6 months, 9 months	Infant weight	Birth to 9 months
Secondary	Infant length at 6 weeks, 3 months, 6 months, 9 months	Infant length	Birth to 9 months
Secondary	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
Secondary	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
Secondary	Placental weight	Weight of placenta in grams	Birth
Secondary	Small for gestational age (SGA)	Under 10th percentile in birth weight for gestational age	Birth