A comparison of the effects of rosiglitazone on endothelial function and arterial stiffness in insulin resistant individuals and normal controls

ISRCTN	ISRCTN50847630
DOI	https://doi.org/10.1186/ISRCTN50847630
Secondary identifying numbers	N0544093589

Submission date: 12/09/2003
Registration date: 12/09/2003
Last edited: 27/09/2011

Recruitment status: Stopped
Overall study status: Stopped
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Ian B Wilkinson
Scientific

Clinical Pharmacology Unit
Level 3, ACCI
Box 110
Addenbrooke's NHS Trust
Cambridge
CB2 2QQ
United Kingdom

Phone	+44 01223-336806
Email	ibw20@cam.ac.uk

Study information

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
Study type	Not Specified
Scientific title
Study objectives	Rosiglitazone: endothelial function and arterial stiffness.
Ethics approval(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Rosiglitazone
Primary outcome measure	Not provided at time of registration
Secondary outcome measures	Not provided at time of registration
Overall study start date	26/01/2001
Completion date	30/09/2003
Reason abandoned (if study stopped)	Lack of funding

Eligibility

Participant type(s)	Patient
Age group	Not Specified
Sex	Not Specified
Target number of participants	24 subjects (PROJ 04/12/2000), 12 additional subjects (PROJ 23/03/2001), total 36
Key inclusion criteria	Not provided at time of registration
Key exclusion criteria	Not provided at time of registration
Date of first enrolment	26/01/2001
Date of final enrolment	30/09/2003

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Clinical Pharmacology Unit

Cambridge
CB2 2QQ
United Kingdom

Sponsor information

Department of Health (UK)
Government

Richmond House
79 Whitehall
London
SW1A 2NL
United Kingdom

Website	http://www.doh.gov.uk

Funders

Funder type

Government

Cambridge Consortium - Addenbrooke's (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan