Plasma homocysteine response to folic acid intervention

ISRCTN	ISRCTN45296887
DOI	https://doi.org/10.1186/ISRCTN45296887
Protocol serial number	N/A
Sponsor	University of Ulster (UK)
Funder	Northern Ireland Chest Heart and Stroke Association (UK)

Submission date: 29/01/2008
Registration date: 05/03/2008
Last edited: 02/02/2011

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Mary Ward
Scientific

Northern Ireland Centre for Food and Health
School of Biomedical Sciences
University of Ulster
Coleraine
BT521SA
United Kingdom

Phone	+44 (0)28 7032 3076
Email	mw.ward@ulster.ac.uk

Study information

Primary study design	Interventional
Study design	Double-blinded, randomised, placebo controlled dose finding trial with folic acid
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	A dose finding trial in ischaemic heart disease patients and healthy controls to determine whether chronic exposure to low-dose folic acid can lower homocysteine
Study objectives	Low dose folic acid (0.2 mg/d) administered chronically will significantly lower plasma homocysteine in ischaemic heart disease (IHD) patients and healthy age-sex matched controls. Previous studies may have overestimated the folic acid dose required to lower homocysteine because of too-short an intervention period to observe the full extent of the response to low folic acid doses and concluded that much higher doses were required for maximal homocysteine-lowering. If the hypothesis is confirmed the findings will have important implications for governments worldwide currently considering food fortification with folic acid, which although primarily aimed at reducing neural tube defects (NTDs), is expected to have important benefits in terms of the primary and secondary prevention of cardiovascular disease (CVD) via a homocysteine-lowering effect.
Ethics approval(s)	The study was approved by the University of Ulster Ethics committee in March 2000 (ref: 01/17).
Health condition(s) or problem(s) studied	Ischaemic heart disease
Intervention	In both IHD and healthy control groups, participants were stratified into tertiles of homocysteine concentration (from the screening blood sample). Subjects in each stratum were then randomised to receive placebo, 0.2, 0.4 or 0.8 mg/d folic acid for a total intervention period of 26 weeks. To maximise compliance, vitamins were distributed every three weeks to the participants homes in seven-day pillboxes. The pillboxes were then collected and any unused pills recorded in order to monitor compliance. Total intervention period of 26 weeks for all treatment arms.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Folic acid
Primary outcome measure(s)	Plasma homocysteine, measured at baseline, 6 weeks and 12 weeks in a subset, and at 26 weeks.
Key secondary outcome measure(s)	1. Serum folate, measured at baseline and at 26 weeks 2. Erythrocyte glutathione reductase activity coefficient (EGRac): an indicator of riboflavin status), measured at baseline 2. Plasma pyridoxal phosphate: an indicator of vitamin B6 status, measured at baseline 3. Serum vitamin B12, measured at baseline
Completion date	31/12/2004

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	200
Key inclusion criteria	1. Male and female, any age 2. IHD Patients: 2.1. Proven myocardial infarction more than three months previously 2.2. IHD on coronary angiography 2.3. A clinical diagnosis of angina confirmed by electrocardiogram (ECG) 3. Control subjects: healthy subjects age- and sex-matched with the IHD group from the local community
Key exclusion criteria	1. IHD patients: 1.1. History of diabetes 1.2. Hepatic or renal disease 1.3. Haematological disorders 1.4. Use of B-vitamin supplements or use of medication known to interfere with folate metabolism 2. Healthy controls in addition had no history of CVD
Date of first enrolment	31/03/2001
Date of final enrolment	31/12/2004

Locations

Countries of recruitment

United Kingdom
Northern Ireland

Study participating centre

Northern Ireland Centre for Food and Health

Coleraine
BT521SA
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/01/2011		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes