Condition category
Circulatory System
Date applied
12/09/2003
Date assigned
12/09/2003
Last edited
27/09/2011
Prospective/Retrospective
Retrospectively registered
Overall trial status
Stopped
Recruitment status
Stopped

Plain English Summary

Not provided at time of registration

Trial website

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 measures

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

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

http://www.doh.gov.uk

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

Results - basic reporting

Publication summary

No publication intended. Trial stopped.

Publication citations

Additional files

Editorial Notes