Optimal Nutrition for Prevention of Hypertension in Pregnancy

NCT04723836 | Active Not Recruiting

• 1 other identifier: 16/NI/0029
• Study Type: interventional
• Target: 2,250
• Locations: 2 countries
• Sites: 3

Brief Summary

The aim of this study is to investigate the role of the 677C→T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene on blood pressure (BP) during pregnancy, and to examine the effect of intervention with riboflavin, alone or in combination with 5-methyltetrahydrofolate (5-MTHF), as a non-drug approach for managing BP in pregnancy in women with the variant TT genotype. In addition, we aim to examine the effect of maternal supplementation with riboflavin, alone or combined with 5-MTHF, on BP in the offspring in early infancy. Study design: A double-blind randomized controlled trial embedded in a large longitudinal observational study in pregnant women will be conducted. Women with a singleton pregnancy who are in their first trimester will be recruited from antenatal clinics in Northern Ireland and the Republic of Ireland. Women interested in the study will provide informed consent, complete a screening questionnaire and will provide a buccal swab to collect DNA to screen for the MTHFR 677C→T polymorphism. Women with multiple pregnancies, a previous NTD-affected pregnancy and those who are taking medication interfering with B-vitamin metabolism will be excluded from participation in the study. At approximately the 16th gestational week (GW), those with the variant TT genotype and age-matched heterozygous women (CT genotype) will be randomised to receive riboflavin (5 mg/day) alone, or in combination with 5-MTHF (400µg/day), or placebo, until the end of pregnancy. A non-fasting blood sample will be collected for biomarker assessment of B-vitamin status and other relevant variables from each participant before intervention and at the 36th GW. At the same time points, anthropometric and BP measurements will be taken. Women will also complete a health and lifestyle questionnaire and a 4-day dietary record. Samples of cord blood, umbilical cord and placenta will be collected after delivery and anthropometric parameters of the newborns will be retrieved postpartum. Maternal and infant BP will be measured 2-4 and 36 months after birth. In parallel with the intervention trial, age-matched pregnant women who do not carry the variant gene (CC genotype) and have not been randomized to treatment, will be monitored in order to control for any changes associated with normal pregnancy in the study outcome measurements. In the pilot phase, the feasibility and acceptability of the study procedures and treatment will be evaluated for clarification of the sample size and refinement of the study protocol.

Conditions

Blood Pressure; Pregnancy

Keywords

Pregnancy; Maternal blood pressure; MTHFR 677TT genotype; Riboflavin; 5-methyltetrahydrofolate; Offspring blood pressure

Outcome Measures

Primary Outcomes (1)

• Maternal Blood Pressure

  Taken according to the clinical guidelines in pregnancy from the UK National Institute for Health and Care Excellence (NICE)

  Change between baseline (12-week gestation) and end of intervention (36-week gestation)

Secondary Outcomes (17)

• Vitamin B12 status

  Change between baseline (12-week gestation) and end of intervention (36-week gestation)

• Plasma homocysteine

  Change between baseline (12-week gestation) and end of intervention (36-week gestation)

• Riboflavin status

  Change between baseline (12-week gestation) and end of intervention (36-week gestation)

• Vitamin B6 status

  Change between baseline (12-week gestation) and end of intervention (36-week gestation)

• Folate status

  Change between baseline (12-week gestation) and end of intervention (36-week gestation)

Study Arms (6)

TT genotype active comparator group

ACTIVE COMPARATOR

5mg riboflavin per day from 16th gestational week

Dietary Supplement: Riboflavin (5mg)

TT genotype experimental group

EXPERIMENTAL

5mg riboflavin + 400µg 5-methyltetrahydrofolate per day from 16th gestational week

Dietary Supplement: Riboflavin (5mg); Dietary Supplement: 5-methyltetrahydrofolate (400µg)

TT genotype placebo group

PLACEBO COMPARATOR

Placebo supplement from 16th gestational week

Dietary Supplement: Placebo

CT genotype active comparator group

ACTIVE COMPARATOR

5mg riboflavin per day from 16th gestational week

Dietary Supplement: Riboflavin (5mg)

CT genotype experimental group

EXPERIMENTAL

5mg riboflavin + 400µg 5-methyltetrahydrofolate per day from 16th gestational week

Dietary Supplement: Riboflavin (5mg); Dietary Supplement: 5-methyltetrahydrofolate (400µg)

CT genotype placebo group

PLACEBO COMPARATOR

Placebo supplement from 16th gestational week

Dietary Supplement: Placebo

Interventions

Riboflavin (5mg) DIETARY_SUPPLEMENT

From 16th week gestation until end of pregnancy

Also known as: Vitamin B2

CT genotype active comparator group; CT genotype experimental group; TT genotype active comparator group; TT genotype experimental group

5-methyltetrahydrofolate (400µg) DIETARY_SUPPLEMENT

From 16th week gestation until end of pregnancy

CT genotype experimental group; TT genotype experimental group

Placebo DIETARY_SUPPLEMENT

From 16th week gestation until end of pregnancy

CT genotype placebo group; TT genotype placebo group

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Women only
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women with a singleton pregnancy who are in their first trimester of pregnancy

You may not qualify if:

• Patients who have a high risk pregnancy, a previous pregnancy with a neural tube defect (NTD) or are the first degree relative of a woman who had a pregnancy affected by NTD or are themselves a sufferer of an NTD
• Women who are taking medication known to interfere with B-vitamin metabolism

Sponsors & Collaborators

• University of Ulster: lead
• DSM Ltd: collaborator
• Public Health Agency (Northern Ireland): collaborator

Study Sites (3)

Letterkenny University Hospital

Letterkenny, Ireland

Location

Northern Health and Social Care Trust

Coleraine, N.Ireland, BT52 1HS, United Kingdom

Location

Western Health and Social Care Trust

Londonderry, N.Ireland, BT47 6SB, United Kingdom

Location

MeSH Terms

Interventions

Riboflavin; 5-methyltetrahydrofolate

Intervention Hierarchy (Ancestors)

Flavins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 3-Ring; Coenzymes; Enzymes and Coenzymes; Pigments, Biological; Biological Factors

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A double-blind randomised controlled trial embedded in a large longitudinal observational study in pregnant women.

Study Record Dates

• First Submitted: January 12, 2021
• First Posted: January 26, 2021
• Study Start: March 1, 2017
• Primary Completion: July 27, 2022
• Study Completion: December 31, 2025
• Last Updated: October 7, 2025

Record last verified: 2025-09

Locations

IE (1); GB (2)