Contact information
Type
Scientific
Primary contact
Dr Ian B Wilkinson
ORCID ID
Contact details
Clinical Pharmacology Unit
Level 3
ACCI
Box 110
Addenbrooke's NHS Trust
Cambridge
CB2 2QQ
United Kingdom
+44 01223-336806
ibw20@cam.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N0544093589
Study information
Scientific title
Acronym
Study hypothesis
Rosiglitazone: endothelial function and arterial stiffness.
Ethics approval
Not provided at time of registration
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Not Specified
Patient information sheet
Condition
Cardiovascular: Endothelial function and arterial stiffness
Intervention
Rosiglitazone has been noted to have effects on the vasculature. We hypothesise that it may improve endothelial function and reduce arterial stiffness. We believe that the effects may be greater in people who are overweight as they tend to have insulin resistance and the actions of rosiglitazone may occur via its insulin-sensitizing effects. The effects may also be partially mediated via nitric oxide dependent mechanisms. We propose to study 12 obese and 12 non-obese subjects. They will be required to attend for three visits, the first of which will last for 30 min and the second and third for around 3 h each. The first visit will be a screening visit during which informed consent will be obtained and inclusion and exclusion criteria checked. Physical examination and medical history will be performed to ensure that it is safe for inclusion in the study. On the second and third visits, measurements of blood pressure, bio-impedance, forearm blood flow and arterial stiffness will be made (all non-invasive). Subjects will then be given a single oral dose of either rosiglitazone 8 mg or placebo. Two hours later, measurements of endothelial function will be made. A 27 gauge needle will be inserted into the left brachial artery under local anaethesia (1% lignocaine). Saline or drugs will be infused at a constant rate of 1.0 ml/min by means of a constant rate infusion pump throughout the duration of the study. Basal blood flow will be recorded after 18 min of 0.9% saline infusion. Acetylcholine will then be co-infused with saline at a dose of 7.5 and 15 ug/min, each dose at 1.0 ml/min for 6 min. There will then be a 18 min washout period during which saline infusion will be given. Sodium nitroprusside will then be co-infused with saline at a dose of 3 and 10 ug/min, each dose at 1.0 ml/min for 6 min. There will then be a further 18 min washout period with saline. L-NG-monomethyl-arginine (L-NMMA) will then be co-infused with saline at a dose of 4 then 8 umol/min, each dose at 1.0 ml/min for 6 min. Further measurements of forearm blood flow will be made during the last 2 min of each infusion period by venous occlusion plethysmography over 1 min. Blood flow will be measured every alternate 3 min for a 3 min period by intermittent inflation of a blood pressure cuff around the upper arm to 40 mmHg. A second cuff will be inflated around the wrist to a pressure of 200 mmHg during measurements of blood flow (maximum duration 3 min) in order to exclude the hand from the circulation during measurements. At the first visit subjects will also undergo measurement of Minimum Forearm Vascular Resistance (MFVR). In order to measure MFVR, a cuff will be inflated around the upper arm to a pressure of 300 mmHg to occlude arterial flow to the forearm for 13 min and then deflated and a measurement of forearm blood flow made by venous occlusion plethysmography. Arterial stiffness will be measured non-invasively using Pulse Wave Analysis (SphygmoCor, PWV Medical, Australia). This involves holding a small pressure sensitive probe against the skin overlying the radial, carotid and femoral arteries in turn. Following the assessment of endothelial function on the second and third visits, subjects will have baseline measurements of arterial stiffness repeated. They will then receive 400 micrograms of salbutamol by inhalation and after values have returned to baseline 500 micrograms of glyceryl trinitrate (GTN) sublingually, with repeat measurements of arterial stiffness immediately after each drug is given. This will allow endothelial function in the large arteries to be assessed. The study will be conducted according to International Conference on Harmonisation (ICH)-Good Clinical Practice (GCP) guidelines.
This trial has stopped due to lack of funding
Intervention type
Drug
Phase
Not Specified
Drug names
Rosiglitazone
Primary outcome measure
Not provided at time of registration
Secondary outcome measures
Not provided at time of registration
Overall trial start date
26/01/2001
Overall trial end date
30/09/2003
Reason abandoned (if study stopped)
Lack of funding
Eligibility
Participant inclusion criteria
Not provided at time of registration
Participant type
Patient
Age group
Not Specified
Gender
Not Specified
Target number of participants
24 subjects (PROJ 04/12/2000), 12 additional subjects (PROJ 23/03/2001), total 36
Participant exclusion criteria
Not provided at time of registration
Recruitment start date
26/01/2001
Recruitment end date
30/09/2003
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Clinical Pharmacology Unit
Cambridge
CB2 2QQ
United Kingdom
Sponsor information
Organisation
Department of Health (UK)
Sponsor details
Richmond House
79 Whitehall
London
SW1A 2NL
United Kingdom
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
Cambridge Consortium - Addenbrooke's (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
Basic results (scientific)
Publication list
No publication intended. Trial stopped.