Clinical trial NCT05949190: Improving Cognition and Gestational Duration With Targeted Nutrition
Official title: Improving Cognition and Gestational Duration With Targeted Nutrition
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Malnutrition in Pregnancy
Preterm Birth
Child Development
Postpartum Depression
Antepartum Depression
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Project Peanut Butter
name: Open Philanthropy
name: United States Department of Agriculture (USDA)
name: Ministry of Health and Sanitation, Sierra Leone
First posted: 2023-07-17
Enrollment: 1600
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: 2x2 factorial design
Primary purpose: TREATMENT

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?

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.

Eligibility criteria: 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

Primary outcomes:
measure: Gestational duration
timeFrame: Enrollment to birth (range 2 to 26 weeks)
measure: Malawi Developmental Assessment Tool (MDAT) global z-score
timeFrame: 9 months post-birth
measure: Adapted Patient Health Questionnaire-9 (PHQ-9) score
timeFrame: 8 weeks after diagnosis with ante- or post-partum depression
Secondary outcomes:
measure: Early preterm birth
timeFrame: Enrollment to 34 weeks' gestation
measure: Birth weight
timeFrame: Birth
measure: Birth length
timeFrame: Birth
measure: Low birth weight
timeFrame: Birth
measure: Malawi Developmental Assessment Test sub-domain z-scores
timeFrame: 9 months after birth
measure: Preterm birth
timeFrame: Enrollment to 37 weeks' gestation
measure: Neonatal mortality
timeFrame: Birth to 28 days of age
measure: Infant mortality
timeFrame: Birth to end of follow-up (9 months)
measure: Depressive symptoms
timeFrame: Through study completion, an average of 1.25 years
measure: Maternal and infant DHA status
timeFrame: From Enrollment to delivery, an average of 15 weeks
measure: Maternal and infant choline status
timeFrame: From Enrollment to delivery, an average of 15 weeks
measure: Maternal weight gain
timeFrame: From Enrollment to delivery, an average of 15 weeks
measure: Post-term delivery
timeFrame: From Enrollment to delivery, an average of 15 weeks
measure: Depression incidence
timeFrame: 8 weeks from time of depression diagnosis
measure: Birth chest circumference
timeFrame: Birth
measure: Birth thigh circumference
timeFrame: Birth
measure: Birth head circumference
timeFrame: Birth
measure: Infant weight at 6 weeks, 3 months, 6 months, 9 months
timeFrame: Birth to 9 months
measure: Infant length at 6 weeks, 3 months, 6 months, 9 months
timeFrame: Birth to 9 months
measure: Infant length-for-age z-score at 6 weeks, 3 months, 6 months, 9 months
timeFrame: Birth to 9 months
measure: Gestational duration
timeFrame: From Enrollment to birth, an average of 15 weeks
measure: Placental weight
timeFrame: Birth
measure: Small for gestational age (SGA)
timeFrame: Birth
Other outcomes:
measure: Intrauterine growth parameters
timeFrame: Subset of participants (enrollment GA <= 24 weeks) to undergo q4-6week serial ultrasounds
measure: Gestational duration by baseline DHA status
timeFrame: From enrollment to birth, an average of 15 weeks
measure: Gestational duration by baseline maternal MUAC
timeFrame: From enrollment to birth, an average of 15 weeks
measure: Gestational duration by enrollment gestational age
timeFrame: From enrollment to birth, an average of 15 weeks
measure: Gestational duration by enrollment maternal age
timeFrame: From enrollment to birth, an average of 15 weeks
measure: Gestational duration by maternal parity
timeFrame: From enrollment to birth, an average of 15 weeks
Locations:
city: Bandajuma
country: Sierra Leone
facility: Bandajuma
state: Southern
city: Bendu
country: Sierra Leone
facility: Bendu Malen
state: Southern
city: Blama Massaquoi
country: Sierra Leone
facility: Blama Massaquoi
state: Southern
city: Futa Peje
country: Sierra Leone
facility: Futa Peje
state: Southern
city: Gbondapi
country: Sierra Leone
facility: Gbondapi
state: Southern
city: Nyandehun
country: Sierra Leone
facility: Nyandehun Malen
state: Southern
city: Potoru
country: Sierra Leone
facility: Potoru
state: Southern
city: Pujehun
country: Sierra Leone
facility: Pujehun Static
state: Southern
city: Sahn
country: Sierra Leone
facility: Sahn Malen
state: Southern
city: Zimmi
country: Sierra Leone
facility: Zimmi
state: Southern
Study officials:
affiliation: Washington University School of Medicine
name: Mark J Manary, MD
role: PRINCIPAL_INVESTIGATOR
References: