Pilot Evaluation of the Effect of Riboflavin Supplementation on Blood Pressure and Possible Effect Modification by the MTHFR C677T Genotype

NCT03151096 | Terminated

• 1 other identifier: SCC1518
• Study Type: interventional
• Target: 133
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

High Blood Pressure; MTHFR C677T Genotype

Outcome Measures

Primary Outcomes (2)

• Blood Pressure

  The aim of this study is to investigate whether supplementing 5mg of riboflavin can decrease blood pressure more effectively compared with placebo

  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

  16 weeks

Secondary Outcomes (2)

• Blood pressure

  16 weeks

• Blood pressure and plasma riboflavin status

  16 weeks

Study Arms (2)

treatment arm

EXPERIMENTAL

5mg Riboflavin pills

Dietary Supplement: Riboflavin

Placebo arm

PLACEBO COMPARATOR

Placebo pills

Dietary Supplement: Placebo

Interventions

Riboflavin DIETARY_SUPPLEMENT

one pill of Riboflavin will be taken orally with water

treatment arm

Placebo DIETARY_SUPPLEMENT

one pill of placebo will be taken orally with water

Placebo arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead
• University of Ulster: collaborator

Study Sites (1)

MRC Clinic Keneba

Keneba, West Kiang, The Gambia

Location

MeSH Terms

Conditions

Hypertension

Interventions

Riboflavin

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Flavins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 3-Ring; Coenzymes; Enzymes and Coenzymes; Pigments, Biological; Biological Factors

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: Field nurse measuring blood pressure, laboratory and data entry staff will be blinded as 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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2017
• First Posted: May 12, 2017
• Study Start: May 2, 2018
• Primary Completion: April 22, 2019
• Study Completion: April 22, 2019
• Last Updated: January 27, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)