Blood Pressure Lowering Effect of B-vitamins in Adults With a Genetic Pre-disposition to Elevated Blood Pressure. (RAFA)

• ClinicalTrials.gov Identifier: NCT04278378
• Recruitment Status: Completed
• First Posted: February 20, 2020
• Last Update Posted: June 18, 2021
• Sponsor: University of Ulster
• Information provided by (Responsible Party): University of Ulster

Study Description

Brief Summary:

Approximately 12% of the world's population have a have a common C677T polymorphism in the gene encoding the folate metabolising enzyme, methylenetetrahydrofolate reductase (MTHFR). Homozygosity for the polymorphism (TT genotype) causes an increased requirement for the B-vitamins folic acid and riboflavin and more importantly results in an increased risk of developing high blood pressure (BP). Previous work from our Centre has demonstrated significantly higher BP in those with the TT genotype. This work has been conducted in cohorts with premature cardiovascular disease (CVD) and hypertension without overt CVD, but the effect in younger, healthier individuals is unexplored. To date our studies have also focused on BP as the primary outcome, but newer markers of vascular health including central pressure and hemodynamics have emerged as superior prognostic indicators of CVD. The effect of the TT genotype on these measures is an area for investigation and may help us understand the mechanism linking the genotype with BP, which is currently unknown. As adults with the TT genotype have increased requirements for riboflavin and folic acid, and BP in TT adults appears to be riboflavin dependent, the influence of these vitamins on central measures is an area for consideration. Study Design This is an observational study investigating the blood pressure profiles of healthy adults aged 18-65 years, stratified by MTHFR genotype. Apparently healthy adults will be recruited from workplaces and the general community across Northern Ireland and screened for the polymorphism via buccal swab. Those with the TT genotype and a similar number of non-TT (i.e. CC/CT) genotype individuals will be contacted and asked to come to a one-off appointment. Brachial BP will be assessed by an electronic BP monitor, central BP and central haemodynamics (augmentation index, augmentation pressure and pulse wave velocity) will be assessed by SphygmoCor XCEL. In addition, anthropometric measurements, health and lifestyle infromation and a blood sample will be obtained. Data will be statistically analysed using SPSS software to if determine differences between gentoype groups exist.

Condition or disease	Intervention/treatment	Phase
Blood Pressure	Dietary Supplement: Riboflavin; Dietary Supplement: Folic acid; Dietary Supplement: Placebo	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 2564 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Blood Pressure Lowering Effect of B-vitamins in Adults With a Genetic Pre-disposition to Elevated Blood Pressure.
• Actual Study Start Date: June 28, 2011
• Actual Primary Completion Date: August 15, 2019
• Actual Study Completion Date: August 15, 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Riboflavin; 1.6 mg riboflavin / day for 24 weeks	Dietary Supplement: Riboflavin; 1.6 mg riboflavin / day for 24 weeks
Experimental: Folic Acid; 0.4 mg folic acid/ day for 24 weeks	Dietary Supplement: Folic acid; 0.4 mg folic acid / day for 24 weeks
Experimental: Riboflavin + Folic Acid; 1.6mg Riboflavin + 0.4 mg Folic Acid / day for 24 weeks	Dietary Supplement: Riboflavin; 1.6 mg riboflavin / day for 24 weeks; Dietary Supplement: Folic acid; 0.4 mg folic acid / day for 24 weeks
Placebo Comparator: Placebo	Dietary Supplement: Placebo

Outcome Measures

Primary Outcome Measures :

1. Blood pressure [ Time Frame: Change from baseline to 24 weeks ]
   Office blood pressure

Secondary Outcome Measures :

1. Central blood pressure [ Time Frame: Change from baseline to 24 weeks ]
   Measured using SphygmoCor device
2. Pulse wave analysis [ Time Frame: Change from baseline to 24 weeks ]
   Measured using SphygmoCor device
3. Pulse wave velocity [ Time Frame: Change from baseline to 24 weeks ]
   Measured using SphygmoCor device
4. Red blood cell riboflavin [ Time Frame: Change from baseline to 24 weeks ]
   Measured using erythrocyte glutathione reductase activity coefficient (EGRAC)
5. Red blood cell folate [ Time Frame: Change from baseline to 24 weeks ]
   Measured by microbiological assay
6. Serum homocysteine [ Time Frame: Change from baseline to 24 weeks ]
   Measured using an immunoassay
7. Plasma vitamin B6 [ Time Frame: Change from baseline to 24 weeks ]
   Measured by High Performance Liquid Chromatography

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• MTHFR 677TT genotype, aged at least 18 years old

Exclusion Criteria:

• Taking supplements containing B-vitamins
• Pregnant or planning to conceive
• Taking medications interfering with folate metabolism
• Renal or gastrointestinal disease

Contacts and Locations

Locations

United Kingdom

Human Intervention Studies Unit, Ulster University

Coleraine, Co.Londonderry, United Kingdom, BT52 1SA

Sponsors and Collaborators

University of Ulster

More Information

• Responsible Party: University of Ulster
• ClinicalTrials.gov Identifier: NCT04278378
• Other Study ID Numbers: REC/11/0081
• First Posted: February 20, 2020
• Last Update Posted: June 18, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Ulster:

Blood pressure; Central hemodynamics; Methylenetetrahydrofolate reductase (MTHFR); Folate polymorphism; Riboflavin; Folic acid

Additional relevant MeSH terms:

Hypertension; Genetic Predisposition to Disease; Vascular Diseases; Cardiovascular Diseases; Disease Susceptibility; Disease Attributes; Pathologic Processes; Folic Acid; Riboflavin; Hematinics; Vitamin B Complex; Vitamins; Micronutrients; Physiological Effects of Drugs; Photosensitizing Agents; Dermatologic Agents