Clinical trial NCT01096693: Effects of Urocortins on Forearm Arterial Blood Flow in Healthy Volunteers (Protocol 2)
Official title: Effects of Urocortins on Forearm Arterial Blood Flow in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Vascular Disease
Heart Disease
Keywords: Urocortin 2
Urocortin 3
Astressin 2B
forearm blood flow
plethysmography
vascular
heart failure
Lead sponsor: University of Edinburgh
Sponsor class: OTHER
Collaborators: name: NHS Lothian
First posted: 2010-03-31
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Forearm blood flow
timeFrame: 2.30 hours
Secondary outcomes:
measure: Net t-PA release
timeFrame: 2.30 hours
Other outcomes:
Locations:
city: Edinburgh
country: United Kingdom
facility: Wellcome Trust Clinical Research Facility, Royal Infirmary of Edinburgh
state: Mid Lothian
Study officials:
affiliation: University of Edinburgh
name: David E Newby, PhD FRCP
role: PRINCIPAL_INVESTIGATOR
References: