Viewing Study NCT03151096



Ignite Creation Date: 2024-05-06 @ 10:05 AM
Last Modification Date: 2024-10-26 @ 12:24 PM
Study NCT ID: NCT03151096
Status: TERMINATED
Last Update Posted: 2020-01-27
First Post: 2017-04-18

Brief Title: Pilot Evaluation of the Effect of Riboflavin Supplementation on Blood Pressure and Possible Effect Modification by the MTHFR C677T Genotype
Sponsor: London School of Hygiene and Tropical Medicine
Organization: London School of Hygiene and Tropical Medicine

Study Overview

Official Title: Pilot Evaluation of the Effect of Riboflavin Supplementation on Blood Pressure and Possible Effect Modification by the MTHFR C677T Genotype
Status: TERMINATED
Status Verified Date: 2020-01
Last Known Status: None
Delayed Posting: No
If Stopped, Why?: The target population with available genotype traveled outside study area and study duration of 19 weeks was long for some participants
Has Expanded Access: False
If Expanded Access, NCT#: N/A
Has Expanded Access, NCT# Status: N/A
Acronym: RiboBP
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 5mgd 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 ie 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 p005 of detecting differences of 388mmHg for SBP and 276mmHg for DBP

Participants within each of the groups will be randomized to riboflavin or placebo in a 11 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 pairs 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 5mgday 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 14090 Then the investigators will test for effect modification according to MTHFR variant

Study Oversight

Has Oversight DMC: None
Is a FDA Regulated Drug?: False
Is a FDA Regulated Device?: False
Is an Unapproved Device?: None
Is a PPSD?: None
Is a US Export?: None
Is an FDA AA801 Violation?: None