Condition category
Circulatory System
Date applied
15/11/2017
Date assigned
17/11/2017
Last edited
10/07/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Low serum levels of vitamin B12 (vB12) have been associated with increased body mass index (BMI) and with increased cardiometabolic outcomes (risk of having diabetes, heart disease or stroke) in several studies. However, it is unclear what the relationship is between vB12 to cardiometabolic risk factors and diseases. This study aims to investigate if there is a relationship between vB12 and indicators of body fat, lipid and glucose (sugar) levels, type 2 diabetes (a condition where blood sugar levels become uncontrolled) and cardiovascular disease (diseases that involve the heart or blood vessels).

Who can participate?
Those who have participants in a previous genome-wide association study (GWAS)

What does the study involve?
This study uses information from a previous genome-wide associate study (GWAS). The researchers take information about serum levels of vB12. The researchers analyse the relationship between vB12 and cardiometabolic risk factors and diseases using publicly available GWAS summary statistics for 15 outcomes.

What are the possible benefits and risks of participating?
There are no benefits or risks of participation

Where is the study run from?
Oslo University Hospital (Norway)

When is the study starting and how long is it expected to run for?
March 2017 to October 2017

Who is funding the study?
Southern and Eastern Norway Regional Health Authority (Norway)

Who is the main contact?
Ms Gunn-Helen Moen
g.h.o.moen@studmed.uio.no

Trial website

Contact information

Type

Scientific

Primary contact

Ms Gunn-Helen Moen

ORCID ID

http://orcid.org/0000-0002-8768-0904

Contact details

Oslo University Hospital
Oslo Universitetssykehus
Aker
Trondheimsveien 235
Oslo
0586
Norway
+47 (0)480 20554
g.h.o.moen@studmed.uio.no

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

123

Study information

Scientific title

Are serum levels of vitamin B12 causally related to cardiometabolic risk factors and disease? A Mendelian randomisation study

Acronym

Study hypothesis

Is there a causal relationship between vB12 and indicators of body fat, lipid- and glucose parameters, T2D and cardiovascular disease?

Ethics approval

Each of the studies used in this project have their own ethical approval and only publicly available data is used

Study design

Observational cohort study

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Other

Trial type

Other

Patient information sheet

No participant information sheet available

Condition

The effect of vitamin B12 on cardiometabolic outcomes

Intervention

11 single nucleotide polymorphisms (SNPs) robustly associated with serum levels of vB12 in a previous genome-wide association study (GWAS) of 45 576 individuals are selected. We performed two sample MR analyses of the relationship between vB12 and cardiometabolic risk factors and diseases using publicly available GWAS summary statistics for 15 outcomes in up to 339224 individuals. Robustness of results is tested with sensitivity analyses using MR Egger regression and Weighted Median estimation, and by performing additional analyses excluding a variant in the FUT2 gene which may be pleiotropic.

This data is taken from publically available summary statistics – which means information regarding genotype/SNP, effect SNP, effect size, standard error, p-values, minor allele frequency etc that is available online.

Summary results statistics on the same SNPs from 15 different GWAS of cardiometabolic outcomes are also taken. The cardiometabolic outcomes are selected on the basis of the following inclusion criteria: the outcome having been associated with vB12 level in observational epidemiological studies and the availability of large meta-GWAS analyses with publicly available summary statistics on the outcome.

Intervention type

Genetic

Phase

Drug names

Primary outcome measure

1. Fasting glucose is measured using genetic data from available GWAS
2. Fasting blood insulin is measured using genetic data from available GWAS
3. HOMA-IR is measured using genetic data from available GWAS
4. HOMA-B is measured using genetic data from available GWAS
5. HbA1c is measured using genetic data from available GWAS
6. Total cholesterol is measured using genetic data from available GWAS
7. LDL cholesterol is measured using genetic data from available GWAS
8. HDL cholesterol is measured using genetic data from available GWAS
9. Triglycerides is measured using genetic data from available GWAS
10. BMI is measured using genetic data from available GWAS
11. Waist-hip ratio is measured using genetic data from available GWAS
12. Leptin is measured using genetic data from available GWAS
13. Body fat is measured using genetic data from available GWAS
14. Coronary artery disease is measured using genetic data from available GWAS
15. Type 2 diabetes is measured using genetic data from available GWAS

Secondary outcome measures

There are no secondary outcome measures

Overall trial start date

01/03/2017

Overall trial end date

15/10/2017

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Participants in the previous genome-wide association study (GWAS)

Participant type

Other

Age group

Adult

Gender

Both

Target number of participants

Number of participants in the studies used varies

Participant exclusion criteria

There is no participant exclusion criteria

Recruitment start date

15/04/2017

Recruitment end date

29/07/2017

Locations

Countries of recruitment

Norway

Trial participating centre

Oslo University Hospital
Oslo Universitetssykehus, Aker Trondheimsveien 235
Oslo
0478
Norway

Sponsor information

Organisation

Oslo University Hospital

Sponsor details

Oslo Universitetssykehus
Aker
Trondheimsveien 235
Oslo
0586
Norway

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

Helse Sør-Øst RHF

Alternative name(s)

Southern and Eastern Norway Regional Health Authority

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Norway

Results and Publications

Publication and dissemination plan

One article of the results is planned. Mendelian Randomization will be used to answer the question if vitamin B12 is causally related to the different cardiometabolic outcomes.

IPD sharing statment:
All data are already publically available. The trialists will include a protocol of how they extracted the data in the publication.

Intention to publish date

01/03/2018

Participant level data

Available on request

Basic results (scientific)

Publication list

2018 results in: https://www.ncbi.nlm.nih.gov/pubmed/29982347

Publication citations

Additional files

Editorial Notes

10/07/2018: Publication reference added. 23/11/2017: Internal review.