Nutritional Support and Prophylaxis Doses of Azithromycin for Pregnant Women - Mumta Pregnant Women Trial

Undernutrition Clinical Trial

— MumtaPW  

Official title:

Nutritional Support and Prophylaxis Doses of Azithromycin for Pregnant Women to Improve Birth Outcomes in the Peri-urban Slums of Karachi, Pakistan -a Randomized Controlled Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04012177
• Other study ID #: 004-VPT-IRB-18
• Status: Active, not recruiting
• Phase: N/A
• Start date: July 22, 2019
• Est. completion date: December 31, 2023

Study information

• Verified date: October 2022
• Source: Vital Pakistan Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This four arm trial envisions to generate robust evidence for use of a fortified balanced energy-protein supplement to pregnant women for at least 6 months, alone versus in combination of Azithromycin (AZM) prophylaxis (two prophylaxis oral doses) versus in combination with both AZM prophylaxis (two prophylaxis oral doses) plus oral Choline and Nicotinamide supplementation; to see the impact on birth weight and length of newborn soon after birth (approximately within 72 hours). This is an open label, community-based, randomized controlled trial in peri-urban settings of Karachi, Pakistan, where the outcome assessor will be blinded. The comparison groups are control arm (only routine ANC care and nutritional counseling), nutrition only arm, nutrition plus AZM arm, and nutrition plus Choline and Nicotinamide arm.

Description:

Maternal under nutrition has a critical role in etiology of poor perinatal outcomes like low birth weight (LBW), accounting for 60-80% of all neonatal deaths and impacting nearly 20 million newborns overall. In Pakistan, nearly half of the households are food insecure with or without hunger. Great disparities exist between urban-rural and within urban disadvantaged populations living in the poorest of slums. In Sindh province alone, 72% of households are food insecure and 50% are with moderate to severe hunger. Around 18% of the married woman of reproductive age in Pakistan, are underweight and deficient of different micronutrients for example, 42% and 41% of women are Vitamin A and Zinc deficient, respectively.. This impacts childhood stunting, wasting, and underweight, prevalence of which, among under-five children is around 44%, 15% and 31%, respectively in Pakistan. WHO antenatal care (ANC) guidelines recommend the use of fortified balanced energy-protein supplements during pregnancy, but there is a lack of guidance on the best product/supplement for use in a particular setting. Until recently, the WHO ANC guidelines has made no recommendations on the use of these supplements in food insecure and undernourished settings. This is an area that required further research. Additionally, there is emerging literature on use of Choline and Nicotinamide during pregnancy and its potential additional impact on birth outcomes including growth and development after prenatal supplementation with Choline and Nicotinamide.

Apart from nutrition supplement, the prophylaxis use of antibiotics, especially AZM is also under strong debate, as many studies have shown improvements in birth outcomes in low middle income settings. The possible mechanism of AZM may be explained through reduction in the risk of maternal infections during pregnancy. A systematic review showed that prophylaxis may reduce the risk of postpartum endometritis, preterm rupture of membranes and gonococcal infection when given routinely to all pregnant women With no effect on birth outcome but there were several biases reported such as high loss to follow-ups and limited numbers of included studies.. Therefore, robust evidence is needed via a field trial in the local context to evaluate the efficacy and effectiveness of the locally-produced, balanced energy-protein supplement alone or in combination with prophylaxis dose of AZM or balanced energy-protein supplement alone or in combination with Choline and Nicotinamide to pregnant woman on maternal and birth outcomes in low-income and food insecure settings. This could help to draw inferences for larger public health policy-making. This investment is specifically aiming to look at what impact a newly formulated nutritional supplement for pregnant and lactating women (PLW) can have on improving birth outcomes and as well as its potential to reduce wasting, stunting and underweight in infants.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1884
• Est. completion date: December 31, 2023
• Est. primary completion date: September 5, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 13 Years to 49 Years

Eligibility

Inclusion Criteria:

• Gestational age between =8 and < 19 weeks confirmed by ultrasound

• Able to give written voluntary informed consent.

• Permanent resident within the surveillance area, i.e. woman should be resident of the area for last 6 months at least to be considered as part of surveillance.

• Willing to spend the whole pregnancy duration after registration in trial within surveillance area until the birth outcome.

• Singleton and viable fetus on ultrasound

• Not working woman, and available for ANC and compliance visits at home.

• Previously not enrolled in pregnant woman trial.

• Previously not enrolled in Lactating woman trials.

Exclusion Criteria:

• Having Mid-upper-arm-circumference of pregnant of =30.5 cm

• Having known food allergies if reported by woman (like peanut, lentils)

Related Conditions & MeSH terms

• Malnutrition
• Undernutrition

Intervention

Dietary Supplement:
• Balanced-energy protein (BEP)
Pregnant women in the intervention arms will receive approximately 800 Kcal/day and around 16-21 gram of protein in a day in the form of ready-to-use supplement.

Drug:
• Azithromycin Tablets
Pregnant women randomized in Arm C will received two doses of 2000 mg of Azithromycin (4 tablets of 500 mg) oral at week 20 and 28 of pregnancy.
• Choline Bitartrate
Pregnant women randomized in Arm D will received 450 mg of Choline orally once daily, starting from week 20 weeks of pregnancy until birth outcome
• Nicotinamide
Pregnant women randomized in Arm D will received 100 mg of Nicotinamide orally once daily, starting from week 20 weeks of pregnancy until birth outcome

Locations

Country	Name	City	State
Pakistan	Peri-urban slum (Rehri Goth)	Karachi	Sindh

Sponsors (2)

Lead Sponsor	Collaborator
Vital Pakistan Trust	Aga Khan University

Country where clinical trial is conducted

Pakistan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Maternal hemoglobin	Assessed in (gm/dl) through Hemocue for all who are agree to assess the difference among four arms	At enrollment and 32 weeks of pregnancy
Other	Maternal Ferritin level	To assess the difference among four arms (ng/ml)	At enrollment and 32 weeks of pregnancy
Other	Maternal Vitamin D level	To assess the difference among four arms (ng/ml)	At enrolment and 32 weeks of pregnancy
Other	Cord blood	Sub-sample - 50 live births in each arm to assess the difference in term of micro- and macro-nutrients and antibodies status.	At birth
Other	Plasma for proteomic analysis	Sub-sample - 50 women in each arm to gain in-depth analysis of proteome which potentially impact (if any) by administration of Azithromycin	At week 19 and 32 of pregnancy
Other	Plasma for Niacin metabolites	Sub-sample - 50 women in each arm to assess the comparison among difference arm to see how these level of metabolites are different among four arm compared to those who received extra daily dose.	At enrolment and 32 weeks of pregnancy
Other	Urine for Choline metabolites	Sub-sample - 50 women in each arm to see how these level of metabolites are different among four arm compared to those who received extra daily dose.	At enrolment and 32 weeks of pregnancy
Other	Magnetic resonance imaging (MRI) of infants (post birth outcomes)	Sub-sample - 50 infants of mothers each arm who will have their birth outcomes to assess brain morphology and volume of infants, using portable MRI machine "Hyperfine".	6 and 12 months of infant's age
Other	Global Scale for Early Development assessment	Sub-sample - 250 infants of mothers each arm who will have their birth outcomes to assess child neurodevelopment progress, using Global Scale for Early Development (GSED)' tool. Mean scores will be compared between the arms; better scores will predict optimal neurodevelopment according to age.	6 and 12 months of infant's age
Other	Mullen assessment	Sub-sample - 250 infants of mothers each arm who will have their birth outcomes to assess child neurodevelopment progress, using 'Mullen' tool. Mean scores will be compared between the arms; better scores will predict optimal neurodevelopment according to age.	6 and 12 months of infant's age
Other	Hammersmith Neurological Examinations	Sub-sample - 250 infants of mothers each arm who will have their birth outcomes to assess child neurodevelopment progress, using 'Hammersmith Neurological Examinations (HINE)' tool. Mean scores will be compared between the arms; better scores will predict optimal neurodevelopment according to age.	6 and 12 months of infant's age
Other	Maternal depression	Maternal depression will be assessed using Patient Health Questionnaire (PHQ-9) during antenatal period and postnatal period. Depression scarring will be comparing scoring between the arm. Further, we will assess and compare depression severity (in any) from 'None minimal' (0-4 score) to 'Severe' (20-27 score)	At week 19 and 32 of pregnancy and then at 6 and 12 month post-partum
Other	Maternal and infant stool microbiome	Sub-sample - 50 women and the infant in each arm to assess and compared for stool microbiome	At week 19 and 32 of pregnancy for mother, and then at 1-2, 3-4 and 5-6 and 12 months post-partum for mother-infant dyad
Other	Maternal and infant stool Lipocalin-2	Sub-sample - 50 women and the infant in each arm to assess and compared Lipocalin-2 (ng/gm)	At week 19 and 32 of pregnancy for mother, and then at 1-2, 3-4 and 5-6 and 12 months post-partum for mother-infant dyad
Other	Maternal and infant stool Carlprotectin	Sub-sample - 50 women and the infant in each arm to assess and compared Carlprotectin (ug/gm)	At week 19 and 32 of pregnancy for mother, and then at 1-2, 3-4 and 5-6 and 12 months post-partum for mother-infant dyad
Other	Maternal and infant stool Myeloperoxidase (MPO)	Sub-sample - 50 women and the infant in each arm to assess and compared Myeloperoxidase (ng/ml*dilution factor)	At week 19 and 32 of pregnancy for mother, and then at 1-2, 3-4 and 5-6 and 12 months post-partum for mother-infant dyad
Other	Maternal and infant stool TaqMan assay	Sub-sample - 50 women and the infant in each arm to assess and compared different colonies	At week 19 and 32 of pregnancy for mother, and then at 1-2, 3-4 and 5-6 and 12 months post-partum for mother-infant dyad
Other	Maternal and infant stool Bifido species	Sub-sample - 50 women and the infant in each arm to assess and compared for Bifido species	At week 19 and 32 of pregnancy for mother, and then at 1-2, 3-4 and 5-6 and 12 months post-partum for mother-infant dyad
Other	Metabolomic work - Maternal during pregnancy	All women who are agreed in each arm, for metabolomic work using 'Volumetric Absorptive Microsampling (VAM)	At enrolment and 32 week of pregnancy
Other	Metabolomic work - Mother-Infant dyad	Sub-sample - 50 women and the infant in each arm for metabolomic work using 'Volumetric Absorptive Microsampling (VAM) Infants - sub-sample of 50 infants of same enrolled women in each arm for metabolomic work using'Volumetric Absorptive Microsampling (VAM)	1-2, 3-4 and 5-6 and 12 months post-partum for mother-infant dyad
Other	Human milk oligosaccharides	Sub-sample - 50 women in each arm to assess and compare breastmilk oligosaccharides	within 72 hours of birth
Other	Breastmilk quality	Sub-sample - 50 women in each arm to assess and compare breastmilk quality (macro-and micro-nutrients)	within 72 hours of birth
Other	Breastmilk microbiome	Sub-sample - 50 women in each arm to assess and compare microbiomes.	within 72 hours of birth
Other	Breastmilk immunoglobulin	Sub-sample - 50 women in each arm to assess immunoglobulins in the breastmilk	within 72 hours of birth
Primary	Birth weight of newborn	Weight of the newborn assess in gram to assess the difference among four arms	To be assessed within 72 hours of birth
Secondary	Birth length of newborn	Length of the newborn assess in cm to assess the difference among four arms	To be assessed within 72 hours of birth