High Blood PressureRiboBPNCT03151096
Pilot Evaluation of the Effect of Riboflavin Supplementation on Blood Pressure and Possible Effect Modification by the MTHFR C677T Genotype
A study testing Riboflavin in people with High Blood Pressure and MTHFR C677T Genotype, run by London School of Hygiene and Tropical Medicine at 1 site in The Gambia.
Trial summary
Hypertension, which results from a combination of multiple lifestyle and genetic factors, is a global public health problem affecting 1 billion people worldwide. The identification of cheap treatment interventions without adverse side effects would be hugely advantageous particularly in low-income settings with high… Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- High Blood Pressure, MTHFR C677T Genotype
- What is being tested?
- Riboflavin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 133 participants
- Where
- 1 siteThe Gambia
- Study dates
- 2 May 2018to 22 Apr 2019
- 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 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy, aged between 18-70 years
- Has provided appropriate ethical consent for involvement in studies relating to genetics.
- Has available genotype data in the Keneba biobank needed for the current study
- Available for the duration of the intervention period
Who cannot join
- Taking vitamin B/multivitamin supplements
- Ongoing pregnancy as confirmed by participant
- History of digestive, hepatic, renal or hematological disorders, dementia
- Epilepsy or taking anti-epileptic medications
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Trial locations and contacts
1 site in 1 country.
About this study
Hypertension, which results from a combination of multiple lifestyle and genetic factors, is a global public health problem affecting 1 billion people worldwide. The identification of cheap treatment interventions without adverse side effects would be hugely advantageous particularly in low-income settings with high prevalence of hypertension such as sub-Saharan Africa where up to 46% of adults are affected.
Emerging evidence links a functional polymorphism in the MTHFR gene (rs1801133 C677T), encoding the folate-metabolising enzyme methylenetetrahydrofolate reductase to high blood pressure in adults. Variation at rs1801133 is relatively common and has 3 genotypes; homozygous "normal" CC, heterozygous CT and homozygous "variant" TT genotypes. Of these genotypes, the homozygous "variant" TT is more strongly associated with a higher BP. The precise mechanism by which MTHFR is associated with BP remains unclear. It has been recently shown in 3 separate randomized controlled trials that BP is highly responsive to riboflavin and that this response is differential by MTHFR rs1801133 genotype. In all these clinical trials, significant reduction in both systolic and diastolic blood pressure was observed in the homozygous variant TT genotype and an intermediate effect seen in those with the heterozygous CT genotype. The aim of this study is to evaluate the effect of riboflavin supplementation on blood pressure in a riboflavin-deplete population as well as comparing plasma riboflavin status before and after supplementation. This will be achieved by conducting a randomized single-blind placebo controlled trial over a period of 16 weeks.
The Investigators will use the Keneba biobank to invite about 100 adults with the CT genotype and a similar number of age-, sex and village-matched CC homozygotes. Participants within each of the groups will be randomized to receive either riboflavin (5mg/d) or a matching placebo which would be supplied on a weekly basis. Blood sample, blood pressure measurement, socio-demographic data and their anthropometric measurements (height, weight, waist and hip circumference and body composition by BIA) will be taken during the initial visit. An additional blood sample will be taken at the end of the study whilst additional BP measurements will be taken respectively at 8 weeks and at the end of the intervention. The possibility that riboflavin deficiency represents a new, easily-correctible causal factor in hypertension in sub-Saharan Africa would require further large-scale interventions if this pilot study yields encouraging results.
Read the detailed description
This is a recall-by-genotype randomized single-blind placebo-controlled micronutrient supplementation trial. The Keneba biobank will be used to identify all potential participants i.e. individuals genotyped for MTHFR C677T for this pilot study.
The Investigators will invite all 163 adults with the CT genotype in the Keneba biobank and a similar number of age- sex- and village-matched CC homozygotes to participate in the study. Field assistants will visit the homes of potentially eligible participants, to provide full information about the purpose and methods of the study, potential risks and benefits, and participants' rights. Participants will then provide written informed consent. The field assistant will ensure that the conversation and consent process occurs in a private area or room, to maintain privacy and confidentiality. After exclusions and non-consenters the investigators anticipate at least 102 subjects per group. Using standard deviation estimates from our own and published literature (14mmHg for SBP and 10mmHg for DBP) the investigators will have 95% confidence (at p<0.05) of detecting differences of 3.88mmHg for SBP and 2.76mmHg for DBP.
Participants within each of the groups will be randomized to riboflavin or placebo in a 1:1 ratio according to a computer generated randomization scheme. This will be done by randomly assigning study numbers within the CT carriers to a treatment group and enrolling participants sequentially from lowest to highest study identification number. The subjects will be randomized upon dispensing the study drug associated with the subject pair's study identification number. Field, clinical, laboratory and data entry staff will be blinded to the genotype of the study participants and to the identity of the treatment arm to which a participant is assigned from the time of randomization to the time of unblinding. The placebos are designed to be indistinguishable from the active drugs. Double-blinding is not possible because subjects randomized to the riboflavin will have yellow urine (a harmless outcome that will be explained to them).
Eligible participants will then be invited for a visit to the MRC Keneba field station. At the initial visit, socio-demographic data and anthropometric measurements (height, weight, waist and hip circumference and body composition by BIA) will be taken. Thereafter, BP will be measured with an automated device in triplicate using a standard protocol by the same investigator who will be blinded to genotype and treatment group. The investigators will also collect 10ml sample of blood for laboratory assessment of vitamin B status. During the intervention phase of the trial, the investigators will supplement participants with 5mg/day of riboflavin or a matching placebo for 16 weeks. The pills will be supplied on a weekly basis with instructions to return any unused pills. Another BP measurement following similar protocol as before will be taken at 8 weeks as well as at 16 weeks after the start of the intervention. Finally, a 10ml blood sample will be collected at 16 weeks. Blood samples will be analysed for riboflavin, homocysteine, red cell folate, cobalamin and pyridoxine. Participants who were randomized to receive placebo will be offered riboflavin supplementation at the end of the study.
The investigators will use multilevel modeling test for a main effect of intervention on delta BP from baseline to 16wk (and repeated at 8wk) adjusted for sex and age. Chi-squared test will be used to test for changes in frequency of raised BP (>140/90). Then the investigators will test for effect modification according to MTHFR variant.
- Conditions
- High Blood Pressure, MTHFR C677T Genotype
- Being tested
- Riboflavin, Placebo
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RiboflavinDietary supplement
one pill of Riboflavin will be taken orally with water
PlaceboDietary supplement
one pill of placebo will be taken orally with water
| Study group | Role | What they receive |
|---|---|---|
| treatment arm | Experimental | 5mg Riboflavin pills Receives: Dietary Supplement: Riboflavin |
| Placebo arm | Placebo comparator | Placebo pills Receives: Dietary Supplement: Placebo |
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 supplementing 5mg of riboflavin can decrease blood pressure more effectively compared with placebo
Measured: 16 weeks
Erythrocyte Glutathione Reductase Activation Coefficient (indicator of riboflavin status)
We will compare EGRAC in those who were randomised to riboflavin supplementation versus placebo
Measured: 16 weeks
Secondary outcomes (2)
Blood pressure
We would like to investigate if there is any effect modification in CC vs CT variants of rs1801133 in the MTHFR gene in response to riboflavin supplementation vs placebo
Measured: 16 weeks
Blood pressure and plasma riboflavin status
We aim to describe the cross-sectional associations at baseline between blood pressure (continuous variable and proportion >140/90mm) and riboflavin status (assessed by the Erythrocyte Glutathione Reductase Activation Coefficient) and MTHFR variants
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 posted12 May 2017
- Study start2 May 2018
- Primary completion22 Apr 2019
- Study completion22 Apr 2019
Why it stopped: The target population with available genotype traveled outside study area and study duration of 19 weeks was long for some participants.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for High Blood PressureStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 133 participants (actual)
Sponsor and investigators
- Lead sponsor
- London School of Hygiene and Tropical Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- University of Ulster
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03151096
- Sponsor's protocol ID
- SCC1518
- Acronym
- RiboBP
- Status last verified
- Jan 2020
- First submitted
- 18 Apr 2017
- Last updated
- 27 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Evaluation of the Effect of Riboflavin Supplementation on Blood Pressure and Possible Effect Modification by the MTHFR C677T Genotype
- ClinicalTrials.gov ID
- NCT03151096
- Acronym / sponsor ID
- RiboBP / SCC1518
- Conditions
- High Blood Pressure, MTHFR C677T Genotype
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The target population with available genotype traveled outside study area and study duration of 19 weeks was long for some participants.
- Enrolment
- 133 participants (actual)
- Lead sponsor
- London School of Hygiene and Tropical MedicineUniversity, hospital or other
- Collaborators
- University of Ulster
- Study start
- 2 May 2018 (actual)
- Primary completion
- 22 Apr 2019 (actual)
- Study completion
- 22 Apr 2019 (actual)
- First posted
- 12 May 2017 (actual)
- 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.
Hypertension, which results from a combination of multiple lifestyle and genetic factors, is a global public health problem affecting 1 billion people worldwide. The identification of cheap treatment interventions without adverse side effects would be hugely advantageous particularly in low-income settings with high prevalence of hypertension such as sub-Saharan Africa where up to 46% of adults are affected.
Emerging evidence links a functional polymorphism in the MTHFR gene (rs1801133 C677T), encoding the folate-metabolising enzyme methylenetetrahydrofolate reductase to high blood pressure in adults. Variation at rs1801133 is relatively common and has 3 genotypes; homozygous "normal" CC, heterozygous CT and homozygous "variant" TT genotypes. Of these genotypes, the homozygous "variant" TT is more strongly associated with a higher BP. The precise mechanism by which MTHFR is associated with BP remains unclear. It has been recently shown in 3 separate randomized controlled trials that BP is highly responsive to riboflavin and that this response is differential by MTHFR rs1801133 genotype. In all these clinical trials, significant reduction in both systolic and diastolic blood pressure was observed in the homozygous variant TT genotype and an intermediate effect seen in those with the heterozygous CT genotype. The aim of this study is to evaluate the effect of riboflavin supplementation on blood pressure in a riboflavin-deplete population as well as comparing plasma riboflavin status before and after supplementation. This will be achieved by conducting a randomized single-blind placebo controlled trial over a period of 16 weeks.
The Investigators will use the Keneba biobank to invite about 100 adults with the CT genotype and a similar number of age-, sex and village-matched CC homozygotes. Participants within each of the groups will be randomized to receive either riboflavin (5mg/d) or a matching placebo which would be supplied on a weekly basis. Blood sample, blood pressure measurement, socio-demographic data and their anthropometric measurements (height, weight, waist and hip circumference and body composition by BIA) will be taken during the initial visit. An additional blood sample will be taken at the end of the study whilst additional BP measurements will be taken respectively at 8 weeks and at the end of the intervention. The possibility that riboflavin deficiency represents a new, easily-correctible causal factor in hypertension in sub-Saharan Africa would require further large-scale interventions if this pilot study yields encouraging results.
Detailed description
This is a recall-by-genotype randomized single-blind placebo-controlled micronutrient supplementation trial. The Keneba biobank will be used to identify all potential participants i.e. individuals genotyped for MTHFR C677T for this pilot study.
The Investigators will invite all 163 adults with the CT genotype in the Keneba biobank and a similar number of age- sex- and village-matched CC homozygotes to participate in the study. Field assistants will visit the homes of potentially eligible participants, to provide full information about the purpose and methods of the study, potential risks and benefits, and participants' rights. Participants will then provide written informed consent. The field assistant will ensure that the conversation and consent process occurs in a private area or room, to maintain privacy and confidentiality. After exclusions and non-consenters the investigators anticipate at least 102 subjects per group. Using standard deviation estimates from our own and published literature (14mmHg for SBP and 10mmHg for DBP) the investigators will have 95% confidence (at p<0.05) of detecting differences of 3.88mmHg for SBP and 2.76mmHg for DBP.
Participants within each of the groups will be randomized to riboflavin or placebo in a 1:1 ratio according to a computer generated randomization scheme. This will be done by randomly assigning study numbers within the CT carriers to a treatment group and enrolling participants sequentially from lowest to highest study identification number. The subjects will be randomized upon dispensing the study drug associated with the subject pair's study identification number. Field, clinical, laboratory and data entry staff will be blinded to the genotype of the study participants and to the identity of the treatment arm to which a participant is assigned from the time of randomization to the time of unblinding. The placebos are designed to be indistinguishable from the active drugs. Double-blinding is not possible because subjects randomized to the riboflavin will have yellow urine (a harmless outcome that will be explained to them).
Eligible participants will then be invited for a visit to the MRC Keneba field station. At the initial visit, socio-demographic data and anthropometric measurements (height, weight, waist and hip circumference and body composition by BIA) will be taken. Thereafter, BP will be measured with an automated device in triplicate using a standard protocol by the same investigator who will be blinded to genotype and treatment group. The investigators will also collect 10ml sample of blood for laboratory assessment of vitamin B status. During the intervention phase of the trial, the investigators will supplement participants with 5mg/day of riboflavin or a matching placebo for 16 weeks. The pills will be supplied on a weekly basis with instructions to return any unused pills. Another BP measurement following similar protocol as before will be taken at 8 weeks as well as at 16 weeks after the start of the intervention. Finally, a 10ml blood sample will be collected at 16 weeks. Blood samples will be analysed for riboflavin, homocysteine, red cell folate, cobalamin and pyridoxine. Participants who were randomized to receive placebo will be offered riboflavin supplementation at the end of the study.
The investigators will use multilevel modeling test for a main effect of intervention on delta BP from baseline to 16wk (and repeated at 8wk) adjusted for sex and age. Chi-squared test will be used to test for changes in frequency of raised BP (>140/90). Then the investigators will test for effect modification according to MTHFR variant.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| treatment arm | Experimental | Dietary Supplement: Riboflavin5mg Riboflavin pills |
| Placebo arm | Placebo comparator | Dietary Supplement: PlaceboPlacebo pills |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Healthy, aged between 18-70 years
- Has provided appropriate ethical consent for involvement in studies relating to genetics.
- Has available genotype data in the Keneba biobank needed for the current study
- Available for the duration of the intervention period
Key exclusion criteria (5 listed)
- Taking vitamin B/multivitamin supplements
- Ongoing pregnancy as confirmed by participant
- History of digestive, hepatic, renal or hematological disorders, dementia
- Epilepsy or taking anti-epileptic medications
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency
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 |
|---|---|---|
| Riboflavinone pill of Riboflavin will be taken orally with water | Dietary supplement | treatment arm |
| Placeboone pill of placebo will be taken orally with water | Dietary supplement | Placebo arm |
Primary outcome
Blood Pressure
Time frame: 16 weeks
The aim of this study is to investigate whether supplementing 5mg of riboflavin can decrease blood pressure more effectively compared with placebo
Erythrocyte Glutathione Reductase Activation Coefficient (indicator of riboflavin status)
Time frame: 16 weeks
We will compare EGRAC in those who were randomised to riboflavin supplementation versus placebo
2 secondary outcomes
Blood pressure
Time frame: 16 weeks
Blood pressure and plasma riboflavin status
Time frame: 16 weeks
Results and safety
The study was stopped early (reason given: The target population with available genotype traveled outside study area and study duration of 19 weeks was long for some participants.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2020.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Riboflavin in people with High Blood Pressure and MTHFR C677T Genotype, run by London School of Hygiene and Tropical Medicine at 1 site in The Gambia.
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 4 inclusion and 5 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: stopped early, as of the sponsor's last update on 27 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in The Gambia. 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?
The study was stopped early (reason given: The target population with available genotype traveled outside study area and study duration of 19 weeks was long for some participants.). 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). The study lists 2 primary outcomes in all. 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 27 Jan 2020.