Participants With the MTHFR 677TT GenotypeRIBOGENENCT02463513
RIBOGENE: Optimisation of Riboflavin Status in Hypertensive Adults With a Genetic Predisposition to Elevated Blood Pressure
A study testing 1.6mg riboflavin (Vitamin B2) and 10mg riboflavin (Vitamin B2) in people with Participants With the MTHFR 677TT Genotype, run by University of Ulster at 3 sites in United Kingdom.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Participants With the MTHFR 677TT Genotype
- What is being tested?
- 1.6mg riboflavin (Vitamin B2) and 10mg riboflavin (Vitamin B2)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 243 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- Feb 2013to Dec 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Over 18 years old
Who cannot join
- History of gastrointestinal; Hepatic; Renal or haematological disorders
- Taking B-vitamin supplements (including multi-vitamins containing B-vitamins), anticonvulsant therapy or any other drugs known to interfere with folate/B-vitamin metabolism.
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
Northern Ireland Clinical Research Facility (NICRF)
Belfast, N.Ireland, BT9 7AB
Human Intervention Studies Unit, University of Ulster
Coleraine, N.Ireland, BT52 1SA
Clinical Translational Research and Innovation Centre (C-TRIC)
Londonderry, N.Ireland, BT47 6SB
About this study
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.
Read the detailed description
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 17.0; 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.
- Being tested
- Placebo comparator, 1.6mg riboflavin (Vitamin B2), 10mg riboflavin (Vitamin B2)
- Keywords
- Riboflavin, Blood pressure, MTHFR, Methylenetetrahydrofolate reductase
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo comparatorDietary supplement
2 week placebo washout + 16 weeks intervention (placebo)
1.6mg riboflavin (Vitamin B2)Dietary supplement
2 week placebo washout + 16 weeks intervention (1.6mg riboflavin per day)
10mg riboflavin (Vitamin B2)Dietary supplement
2 week placebo washout + 16 weeks intervention (10mg riboflavin per day)
| Study group | Role | What they receive |
|---|---|---|
| Treatment 1 | Placebo comparator | Not described Receives: Dietary Supplement: Placebo comparator |
| Treatment 2 | Active comparator | Not described Receives: Dietary Supplement: 1.6mg riboflavin (Vitamin B2) |
| Treatment 3 | Active comparator | Not described Receives: Dietary Supplement: 10mg riboflavin (Vitamin B2) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood Pressure
The aim of this study is to investigate whether a low dose supplemental level (10mg/d) of riboflavin can decrease blood pressure more effectively than the dietary level (1.6mg/d) by optimising riboflavin status and normalising MTHFR activity.
Measured: 16 weeks
Secondary outcomes (5)
Erythrocyte Glutathione Reductase Activation Coefficient (EGRAC)
Indicator of Vitamin B2 status
Measured: 16 weeks
Plasma Homocysteine
Measured: 16 weeks
Red cell folate
Measured: 16 weeks
Vitamin B12
Measured: 16 weeks
Vitamin B6
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2015 (estimated)
- Study startFeb 2013
- Primary completionDec 2017 (estimated)
- Study completionDec 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Participants With the MTHFR 677TT GenotypeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 243 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Ulster
- Sponsor type
- University, hospital or other
- Collaborators
- dsm-firmenich Switzerland AG
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02463513
- Sponsor's protocol ID
- OREC 12/NI/0136
- Acronym
- RIBOGENE
- Status last verified
- May 2016
- First submitted
- 2 Jun 2015
- Last updated
- 13 May 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RIBOGENE: Optimisation of Riboflavin Status in Hypertensive Adults With a Genetic Predisposition to Elevated Blood Pressure
- ClinicalTrials.gov ID
- NCT02463513
- Acronym / sponsor ID
- RIBOGENE / OREC 12/NI/0136
- Keywords
- Riboflavin, Blood pressure, MTHFR, Methylenetetrahydrofolate reductase
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 243 participants (actual)
- Lead sponsor
- University of UlsterUniversity, hospital or other
- Collaborators
- dsm-firmenich Switzerland AG
- Study start
- Feb 2013
- Primary completion
- Dec 2017 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 4 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 17.0; 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Treatment 1 | Placebo comparator | Dietary Supplement: Placebo comparator |
| Treatment 2 | Active comparator | Dietary Supplement: 1.6mg riboflavin (Vitamin B2) |
| Treatment 3 | Active comparator | Dietary Supplement: 10mg riboflavin (Vitamin B2) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Over 18 years old
Key exclusion criteria (2 listed)
- History of gastrointestinal; Hepatic; Renal or haematological disorders
- Taking B-vitamin supplements (including multi-vitamins containing B-vitamins), anticonvulsant therapy or any other drugs known to interfere with folate/B-vitamin metabolism.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo comparator2 week placebo washout + 16 weeks intervention (placebo) | Dietary supplement | Treatment 1 |
| 1.6mg riboflavin (Vitamin B2)2 week placebo washout + 16 weeks intervention (1.6mg riboflavin per day) | Dietary supplement | Treatment 2 |
| 10mg riboflavin (Vitamin B2)2 week placebo washout + 16 weeks intervention (10mg riboflavin per day) | Dietary supplement | Treatment 3 |
Primary outcome
Blood Pressure
Time frame: 16 weeks
The aim of this study is to investigate whether a low dose supplemental level (10mg/d) of riboflavin can decrease blood pressure more effectively than the dietary level (1.6mg/d) by optimising riboflavin status and normalising MTHFR activity.
5 secondary outcomes
Erythrocyte Glutathione Reductase Activation Coefficient (EGRAC)
Time frame: 16 weeks
Plasma Homocysteine
Time frame: 16 weeks
Red cell folate
Time frame: 16 weeks
Vitamin B12
Time frame: 16 weeks
Vitamin B6
Time frame: 16 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2016.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 1.6mg riboflavin (Vitamin B2) and 10mg riboflavin (Vitamin B2) in people with Participants With the MTHFR 677TT Genotype, run by University of Ulster at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood Pressure (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2016.