Participants With the MTHFR 677TT Genotype Clinical Trial
Official title:
RIBOGENE: Optimisation of Riboflavin Status in Hypertensive Adults With a Genetic Predisposition to Elevated Blood Pressure
Approximately 10% of the world's population have a particular genetic makeup (known as the
TT genotype) that may increase their risk of having higher blood pressure. Previous work
conducted by the investigators research group at the University of Ulster, in collaboration
with clinical colleagues from across Northern Ireland, in premature CVD patients and
hypertensive adults generally has demonstrated that a dietary level of riboflavin (1.6mg/d)
decreases blood pressure, specifically in those with the TT genotype. To date, the blood
pressure lowering effects of higher doses of riboflavin in individuals with the TT genotype
is not known. The aim of this study is to investigate whether supplementation with
riboflavin at a low dose supplemental level (10mg/d) can decrease blood pressure more
effectively than the dietary level (1.6mg/d) by optimising riboflavin status and normalising
MTHFR activity. This aim will be achieved by conducting a double-blind placebo-controlled
intervention study over a 16 week period.
Participants will be recruited from cohorts screened for the methylenetetrahydrofolate
reductase (MTHFR) C677T polymorphism. Those identified with the TT genotype (homozygous for
the polymorphism) that wish to participate in this research will be asked to attend a
baseline and week-16 appointment and will be asked to take a daily riboflavin (1.6 or
10mg/d) or placebo capsule for the duration of the study. At each appointment a blood sample
will be taken and blood pressure, height, weight and waist circumference will be measured.
If the results of this study show that intervention with a higher dose of riboflavin can
lower blood pressure more effectively in individuals with the TT genotype this will have
important implications for those responsible for the management of blood pressure. The
findings will be of particular relevance in populations with a higher prevalence of the
polymorphism.
Recruitment - Potential participants will be identified and recruited via GP practices,
hospital outpatient clinics, pharmacies and workplaces throughout Northern Ireland. A letter
of invitation and a study package containing a participant information sheet to explain the
study, a consent form and a buccal swab DNA collection kit will be included.
Inclusion / Exclusion The main inclusion criteria are that individuals must have the TT
genotype. Exclusion criteria includes a history of gastrointestinal, hepatic, renal or
haematological disorders, B-vitamin supplements consumer (including multi-vitamins
containing B-vitamins), anticonvulsant therapy or any other drugs known to interfere with
folate/B-vitamin metabolism. Suitable individuals that participated in the screening process
will be contacted and invited to participate in the intervention study. Participants will be
given at least forty eight hours to consider the written information and decide if they wish
to participate.
Study Design
Participants with the TT genotype who have given informed consent will be stratified by
blood pressure and subsequently randomised to receive placebo, low dose (1.6mg/d) or low
supplemental dose (10mg/d) riboflavin for the 16 week intervention period. It is important
to be aware that no upper limit has been established for this water-soluble B-vitamin and
there are no safety concerns regarding these doses of riboflavin or indeed higher doses
(including 25mg/d) administered in previous studies (Madigan et al. 1998).
Participants, depending on geographical location, will be asked to attend two appointments
(Baseline and week 16) at the participants local GP Practice, The Clinical Translational
Research and Innovation Centre (CTRIC) at Altnagelvin Area Hospital, The Welcome
Trust-Wolfson Northern Ireland Clinical Research Facility (NICRF) Belfast City Hospital, the
Northern Ireland Centre for Food & Health (NICHE) (University of Ulster, Coleraine) or at
another convenient location. At both sampling points blood pressure (SBP/DBP mmHg) will be
measured, a 30ml blood sample will be taken by a trained phlebotomist and the patient's
height (m), weight (kg), waist circumference (cm) and BMI (kg/m2) will be measured. A
detailed health and lifestyle questionnaire will collect information on medical and family
history, medication and supplement use and dietary intake.
Statistical analysis Statisticalanalysis will be performed using SPSS (Statistical Package
for Social Sciences, Version 17.0Íž SPSS UK Ltd, Chersey, United Kingdom). Data that is not
normally distributed will be transformed to obtain normality before statistical analysis is
performed. Data will then be analysed to investigate if any differences exist in the BP
response between the two riboflavin treatment groups.
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Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention