Condition category
Circulatory System
Date applied
29/01/2008
Date assigned
05/03/2008
Last edited
02/02/2011
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Mary Ward

ORCID ID

Contact details

Northern Ireland Centre for Food and Health
School of Biomedical Sciences
University of Ulster
Coleraine
BT521SA
United Kingdom
+44 (0)28 7032 3076
mw.ward@ulster.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

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

Acronym

Study hypothesis

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

The study was approved by the University of Ulster Ethics committee in March 2000 (ref: 01/17).

Study design

Double-blinded, randomised, placebo controlled dose finding trial with folic acid

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

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 names

Folic acid

Primary outcome measures

Plasma homocysteine, measured at baseline, 6 weeks and 12 weeks in a subset, and at 26 weeks.

Secondary outcome measures

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

Overall trial start date

31/03/2001

Overall trial end date

31/12/2004

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

n = 200 (100 patients, 100 controls)

Participant 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

Recruitment start date

31/03/2001

Recruitment end date

31/12/2004

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Northern Ireland Centre for Food and Health
Coleraine
BT521SA
United Kingdom

Sponsor information

Organisation

University of Ulster (UK)

Sponsor details

c/o Mary Ward
School of Biomedical Sciences
Cromore Road
Coleraine
BT52 1SA
United Kingdom
+44 (0)28 7032 3076
mw.ward@ulster.ac.uk

Sponsor type

University/education

Website

http://www.ulster.ac.uk/

Funders

Funder type

Charity

Funder name

Northern Ireland Chest Heart and Stroke Association (UK)

Alternative name(s)

NICHS

Funding Body Type

private sector organisation

Funding Body Subtype

professional associations and societies

Location

Ireland

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/20980493

Publication citations

  1. Results

    Tighe P, Ward M, McNulty H, Finnegan O, Dunne A, Strain J, Molloy AM, Duffy M, Pentieva K, Scott JM, A dose-finding trial of the effect of long-term folic acid intervention: implications for food fortification policy., Am. J. Clin. Nutr., 2011, 93, 1, 11-18, doi: 10.3945/ajcn.2010.29427.

Additional files

Editorial Notes