Effectiveness of a Micronutrient Supplement to Lower Plasma Homocysteine MDEG2 Pilot Supplementation Trial

NCT03431597 | Completed Phase 2

• 1 other identifier: SCC 1575
• Study Type: interventional
• Target: 298
• Locations: 1 country
• Sites: 1

Brief Summary

This micronutrient supplementation study is a 3-arm randomized controlled trial, unblinded, with 125 women per arm. Non-pregnant, non-lactating healthy women of reproductive age in West Kiang, The Gambia, will be randomized to 12 weeks of daily supplementation of either a) novel micronutrient supplement, b) a United Nations International Multiple Micronutrient Preparation (UNIMMAP) tablet or c) no intervention (control). The novel micronutrient supplement is a drink powder providing 800 µg folic acid, 5.2 µg cyanocobalamin (B12), 2.8 mg Riboflavin-5'-phosphate (B2), and 4g trimethylglycine (betaine). UNIMMAP contains 15 micronutrients at the Recommended Daily Allowance level. The aim is to test the effectiveness of the supplements on correcting micronutrient deficiencies in the dry season and to reduce homocysteine levels. The hypothesis is that the new drink powder will be the most effective supplement, causing a reduction in 1 µmol/L compared to the control group after supplementation. The supplements will be supplied to participants on a daily basis by Community-based Birth Attendants (CBCs). The CBCs will observe consumption of the supplement. The novel micronutrient supplement will be provided in powder form with instructions to dissolve one sachet in a cup of 200ml water. UNIMMAP will be provided in capsule form to be taken with water. Women will provide one 10ml fasted venous blood sample at baseline and another after 6 and 12 weeks of supplementation. At each time point they will also have their blood pressure and anthropometry assessed and provide a urine pregnancy test. Correcting micronutrient deficiencies is extremely important for the long-term health of women, and in particular around the time of conception and throughout pregnancy since micronutrients are needed for the proper physical and cognitive development of the baby. Certain micronutrients are required for adding a methyl group to places on DNA ('DNA methylation'). The pattern of these methyl groups can help determine whether a gene is switched on or off. Correct functioning of DNA methylation processes is therefore of critical importance for fetal development. High levels of homocysteine can impede DNA methylation, therefore supplements that reduce homocysteine may not only be beneficial for the mother but also for the developing child. The most effective supplement in this trial will be considered for testing in larger pregnancy trials.

Conditions

Micronutrient Deficiencies; Hyperhomocysteinemia

Outcome Measures

Primary Outcomes (1)

• Difference in plasma homocysteine concentration between the drink powder and control arms at end-lineplasma Hcy vs control

  To compare the effect of a novel micronutrient supplement taken daily for 12 weeks in the dry season on lowering plasma homocysteine versus the control group supplement taken daily for 12 weeks in the dry season on lowering plasma homocysteine (Hcy) versus the control group

  after 12 weeks

Secondary Outcomes (3)

• Difference in plasma homocysteine concentration between the drink powder and UNIMMAP arms at end-line

  after 12 weeks

• Difference in plasma homocysteine concentration between the the drink powder and UNIMMAP arms at mid-line

  after 6 weeks

• Difference in blood pressure (systolic and diastolic) and pulse between the drink powder and control arms at end-line

  after 12 weeks

Study Arms (3)

oral nutritional supplementation

EXPERIMENTAL

Daily novel micronutrient supplement: 800 μg folic acid, 5.2 μg cyanocobalamin (B12), 2.8 mg Riboflavin-5'- phosphate (B2), 4g trimethylglycine (betaine) in drink powder form. The drink will be dissolved in 200ml of water and taken daily for 12 weeks

Dietary Supplement: novel micronutrient

oral nutritional supplementation, UNIMMAP

ACTIVE COMPARATOR

The United Nations Multiple Micronutrient Preparation (UNIMMAP) supplement is a capsule containing 15 micronutrients (vitamins A, D, E, B1, B2, B6, B12, C, Niacin, Folic Acid, Fe, Zn, Cu, I, Se) at the Recommended Daily Allowance level. UNIMMAP will be provided in capsule form and taken daily with water for 12 weeks.

Dietary Supplement: existing micronutrient supplement, UNIMMAP

control

NO INTERVENTION

no treatment will be given to this group observation only (no placebo)

Interventions

novel micronutrient DIETARY_SUPPLEMENT

The supplements will be supplied to participants on a daily basis. The novel micronutrient supplement will be provided in powder form with instructions to dissolve one sachet in 250ml of clean water

oral nutritional supplementation

existing micronutrient supplement, UNIMMAP DIETARY_SUPPLEMENT

UNIMMAP will be provided in tablet form and given one daily

oral nutritional supplementation, UNIMMAP

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: A list of eligible women within West Kiang will be generated using the MRCG Keneba Health and Demographic Surveillance System (HDSS) database
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Pre-menopausal women aged 18-45 years
• Non-pregnant, confirmed by pregnancy urine test at eligibility screen
• Non-lactating (at least 9 months post-partum)
• No plan to conceive in the ensuing 3 months, asked verbally by field worker
• No plans to travel
• Healthy with no current illness and no chronic health problems, asked verbally by field worker

You may not qualify if:

• Known history of chronic illness (particularly cardiovascular disease, renal disease, thyroid disease, cancer)
• Taking B vitamin or multivitamin supplements.
• Taking medication for prevention of seizures (e.g. Carbamazepine).

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead

Study Sites (1)

Keneba Field Station

Banjul, The Gambia

Location

Related Publications (1)

• James PT, Jawla O, Mohammed NI, Ceesay K, Akemokwe FM, Sonko B, Sise EA, Prentice AM, Silver MJ. A novel nutritional supplement to reduce plasma homocysteine in nonpregnant women: A randomised controlled trial in The Gambia. PLoS Med. 2019 Aug 13;16(8):e1002870. doi: 10.1371/journal.pmed.1002870. eCollection 2019 Aug.

  PMID: 31408467 DERIVED

MeSH Terms

Conditions

Hyperhomocysteinemia

Condition Hierarchy (Ancestors)

Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Malabsorption Syndromes; Metabolic Diseases; Nutritional and Metabolic Diseases; Vitamin B Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders

Study Officials

• Andrew Prentice, PhD

  Medical Research Council Unit, The Gambia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 3-arm randomized controlled trial, unblinded, with 125 women per arm.

Study Record Dates

• First Submitted: January 26, 2018
• First Posted: February 13, 2018
• Study Start: April 26, 2018
• Primary Completion: July 20, 2018
• Study Completion: November 26, 2018
• Last Updated: January 22, 2019

Record last verified: 2019-01

Locations

TH (1)