Effects of Urocortins on Forearm Arterial Blood Flow in Healthy Volunteers

NCT ID: NCT01049542

Last Updated: 2010-11-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

6 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-05-31

Study Completion Date

2010-07-31

Brief Summary

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Impairment of the heart's pumping capacity (heart failure) remains a major clinical problem with a poor prognosis and the search for novel treatments remains an important area of research.

Urocortins are proteins that appear to increase blood flow and heart pumping activity. There has been particular interest in the role of Urocortins 2 \& 3 (subtypes of Urocortins) in heart failure.

In this study, we will examine the effects and mechanisms of Urocortins 2 \& 3 and the Corticotrophin Releasing Hormone Receptor Type 2 (CRH-R2) receptor (through which urocortins act) on forearm blood flow and release of natural blood clot dissolving factors in the forearm circulation of healthy volunteers.

In this study, we will look at the role of the lining of the blood vessel (endothelium) in response to urocortin types 2 and 3. We hypothesise that urocortins 2 \& 3 act via the endothelium to cause dilatation of the blood vessels and release of tissue-plasminogen activating factor (blood clot dissolving factor). We also hypothesise that urocortins have a role in maintaining the normal baseline level of blood flow in forearm arteries. In addition to the above, we will also look at the effect of temporarily blocking the effect of urocortins, using a specially designed blocker drug (Astressin 2B).

Utilising the well-established technique of 'forearm venous occlusion plethysmography', we will be able to focus on the local effects of urocortins on arterial blood flow in forearm vessels, without affecting this system in the body as a whole.

Detailed Description

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Conditions

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Vascular Disease Heart Disease

Keywords

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Astressin 2B Forearm blood flow vascular plethysmography heart failure

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

SINGLE

Participants

Study Groups

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Astressin 2B

Healthy volunteers will receive incremental doses of intra arterial Astressin 2B (a selective and potent Urocortin 2 \& 3 antagonist). This serves as a dose finding Protocol for Astressin 2B, which will be used in subsequent protocols.

Group Type EXPERIMENTAL

Astressin 2B

Intervention Type DRUG

After an initial saline washout, increasing doses of Astressin 2B (at 0.032, 0.32, 3.2, 32, 320 and 3200 pmol/min) will be infused, for 10 minutes at each dose,intra arterially using forearm venous occlusion plethysmography. Forearm blood flow will be measured with each incremental dose of Astressin 2B.

Interventions

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Astressin 2B

After an initial saline washout, increasing doses of Astressin 2B (at 0.032, 0.32, 3.2, 32, 320 and 3200 pmol/min) will be infused, for 10 minutes at each dose,intra arterially using forearm venous occlusion plethysmography. Forearm blood flow will be measured with each incremental dose of Astressin 2B.

Intervention Type DRUG

Other Intervention Names

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Forearm vascular study

Eligibility Criteria

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Inclusion Criteria

* Healthy male volunteers between 18 - 65 years (inclusive)

Exclusion Criteria

* Lack of informed consent
* Age \<18 years \> 65 years
* Current involvement in a clinical trial
* Severe or significant co-morbidity including bleeding diathesis, renal or hepatic failure
* Smoker
* History of anaemia
* Recent infective/inflammatory condition
* Recent blood donation (prior 3 months)
* Positive baseline urine test for drugs of abuse (including cannabinoids, benzodiazepines, opiates, cocaine and amphetamines)
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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University of Edinburgh

OTHER

Sponsor Role lead

Responsible Party

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University of Edinburgh

Principal Investigators

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David E Newby, PhD FRCP

Role: PRINCIPAL_INVESTIGATOR

University of Edinburgh

Locations

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Wellcome Trust Clinical Research Facility, Royal Infirmary of Edinburgh

Edinburgh, Mid Lothian, United Kingdom

Site Status

Countries

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United Kingdom

Other Identifiers

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SV.Protocol1

Identifier Type: -

Identifier Source: org_study_id