Contact information
Type
Scientific
Primary contact
Prof Morris Brown
ORCID ID
Contact details
University of Cambridge
Clinical Pharmacology Unit
Level 6
ACCI
Hills Road
Addenbrooke's Hospital
Cambridge
CB2 2QQ
United Kingdom
+44 (0)1223 336743
mjb14@medschl.cam.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
Brown HSR/06/97
Study information
Scientific title
Pilot study for CHAOS-Two (Cambridge Heart Anti-Oxidant study: trial with other vitamins)
Acronym
CHAOS-Two
Study hypothesis
The overall aim of CHAOS-Two is to determine whether folic acid reduces the incidence of myocardial infarction. The principle current hypothesis on which to base expectation of benefit is a well documented effect of folic acid to reduce plasma levels of the amino acid, homocysteine, which has been found in several prospective and case-control studies to be a major risk factor for atherosclerotic diseases. CHAOS-Two should thus provide a test of the homocysteine hypothesis. However, an additional pathway through which folic acid may be beneficial is the so-called salvage pathway to synthesis of the co-factor, tetrahydrobiopterin, required for Nitric Oxide (NO) synthesis. The principle requirement of the pilot study is to permit calculation of numbers required for the main study, using the relative risk of homocysteine in the epidemiological studies, and the average difference after 1 year between homocysteine levels in the folate and placebo groups. The pilot will also establish whether folic acid had the additional action via NO.
Ethics approval
Not provided at time of registration
Study design
Randomised placebo controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Prevention
Patient information sheet
Condition
Heart disease
Intervention
1. Folate 5 mg
2. Placebo
Intervention type
Other
Phase
Not Specified
Drug names
Primary outcome measures
1. Main Study
1.1. Fatal or non-fatal myocardial infarction.
2. Pilot Study
2.1. Percentage of patients with B12 deficiency on entry despite normal Hb and MCV, and patients becoming B12 deficient at follow-ups.
2.2. Percentage change in plasma homocysteine and plasma tetrahydrobiopterin in response to folic acid, and variation in these over one year.
2.3. Compliance with treatment addeddes from rise in rbc folate in active group.
2.4. Estimate of number of eligible patients likely to be recruited annually.
Secondary outcome measures
Not provided at time of registration
Overall trial start date
01/07/1997
Overall trial end date
01/07/1999
Reason abandoned
Eligibility
Participant inclusion criteria
1. Patients admitted for coronary angiograph
2. Stable angina
3. Positive coronary angiogram
Participant type
Patient
Age group
Not Specified
Gender
Not Specified
Target number of participants
Not provided at time of registration
Participant exclusion criteria
Patients with a macrocytic anaemia (Hb <10, mean cell volume [MCV] >100) will be excluded from the pilot unless their serum B12 is normal. To be revised if indicated by follow-up results of Hb and B12 pilot.
Recruitment start date
01/07/1997
Recruitment end date
01/07/1999
Locations
Countries of recruitment
United Kingdom
Trial participating centre
University of Cambridge
Cambridge
CB2 2QQ
United Kingdom
Sponsor information
Organisation
NHS R&D Regional Programme Register - Department of Health (UK)
Sponsor details
The Department of Health
Richmond House
79 Whitehall
London
SW1A 2NL
United Kingdom
+44 (0)20 7307 2622
dhmail@doh.gsi.org.uk
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
NHS Executive Eastern (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
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