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

Primary Purpose

Blood Pressure

Status
Completed
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Riboflavin
Folic acid
Placebo
Sponsored by
University of Ulster
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Blood Pressure focused on measuring Blood pressure, Central hemodynamics, Methylenetetrahydrofolate reductase (MTHFR), Folate polymorphism, Riboflavin, Folic acid

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Human Intervention Studies Unit, Ulster University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Experimental

Placebo Comparator

Arm Label

Riboflavin

Folic Acid

Riboflavin + Folic Acid

Placebo

Arm Description

1.6 mg riboflavin / day for 24 weeks

0.4 mg folic acid/ day for 24 weeks

1.6mg Riboflavin + 0.4 mg Folic Acid / day for 24 weeks

Outcomes

Primary Outcome Measures

Blood pressure
Office blood pressure

Secondary Outcome Measures

Central blood pressure
Measured using SphygmoCor device
Pulse wave analysis
Measured using SphygmoCor device
Pulse wave velocity
Measured using SphygmoCor device
Red blood cell riboflavin
Measured using erythrocyte glutathione reductase activity coefficient (EGRAC)
Red blood cell folate
Measured by microbiological assay
Serum homocysteine
Measured using an immunoassay
Plasma vitamin B6
Measured by High Performance Liquid Chromatography

Full Information

First Posted
February 17, 2020
Last Updated
June 11, 2021
Sponsor
University of Ulster
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1. Study Identification

Unique Protocol Identification Number
NCT04278378
Brief Title
Blood Pressure Lowering Effect of B-vitamins in Adults With a Genetic Pre-disposition to Elevated Blood Pressure.
Acronym
RAFA
Official Title
Blood Pressure Lowering Effect of B-vitamins in Adults With a Genetic Pre-disposition to Elevated Blood Pressure.
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
June 28, 2011 (Actual)
Primary Completion Date
August 15, 2019 (Actual)
Study Completion Date
August 15, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Ulster

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Blood Pressure
Keywords
Blood pressure, Central hemodynamics, Methylenetetrahydrofolate reductase (MTHFR), Folate polymorphism, Riboflavin, Folic acid

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
2564 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Riboflavin
Arm Type
Active Comparator
Arm Description
1.6 mg riboflavin / day for 24 weeks
Arm Title
Folic Acid
Arm Type
Experimental
Arm Description
0.4 mg folic acid/ day for 24 weeks
Arm Title
Riboflavin + Folic Acid
Arm Type
Experimental
Arm Description
1.6mg Riboflavin + 0.4 mg Folic Acid / day for 24 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Dietary Supplement
Intervention Name(s)
Riboflavin
Intervention Description
1.6 mg riboflavin / day for 24 weeks
Intervention Type
Dietary Supplement
Intervention Name(s)
Folic acid
Intervention Description
0.4 mg folic acid / day for 24 weeks
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Blood pressure
Description
Office blood pressure
Time Frame
Change from baseline to 24 weeks
Secondary Outcome Measure Information:
Title
Central blood pressure
Description
Measured using SphygmoCor device
Time Frame
Change from baseline to 24 weeks
Title
Pulse wave analysis
Description
Measured using SphygmoCor device
Time Frame
Change from baseline to 24 weeks
Title
Pulse wave velocity
Description
Measured using SphygmoCor device
Time Frame
Change from baseline to 24 weeks
Title
Red blood cell riboflavin
Description
Measured using erythrocyte glutathione reductase activity coefficient (EGRAC)
Time Frame
Change from baseline to 24 weeks
Title
Red blood cell folate
Description
Measured by microbiological assay
Time Frame
Change from baseline to 24 weeks
Title
Serum homocysteine
Description
Measured using an immunoassay
Time Frame
Change from baseline to 24 weeks
Title
Plasma vitamin B6
Description
Measured by High Performance Liquid Chromatography
Time Frame
Change from baseline to 24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Facility Information:
Facility Name
Human Intervention Studies Unit, Ulster University
City
Coleraine
State/Province
Co.Londonderry
ZIP/Postal Code
BT52 1SA
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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