Vascular DiseaseNCT01096693
Effects of Urocortins on Forearm Arterial Blood Flow in Healthy Volunteers (Protocol 2)
A study testing Urocortin 2, Urocortin 3 in people with Vascular Disease and Heart Disease, run by University of Edinburgh at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Vascular Disease, Heart Disease
- What is being tested?
- Urocortin 2, Urocortin 3
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Aug 2010to 31 Aug 2014
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy male volunteers between 18 - 65 years (inclusive)
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Wellcome Trust Clinical Research Facility, Royal Infirmary of Edinburgh
Edinburgh, Mid Lothian, EH16 4SA
About this study
Official title: Effects of Urocortins on Forearm Arterial Blood Flow in Healthy Volunteers
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.
Read more
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.
- Conditions
- Vascular Disease, Heart Disease
- Being tested
- Urocortin 2, Urocortin 3, Saline placebo
- Keywords
- Urocortin 2, Urocortin 3, Astressin 2B, forearm blood flow, plethysmography, vascular, heart failure
- Medical subject headings
- Vascular Diseases, Heart Diseases, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Urocortin 2, Urocortin 3Drug
Also called Forearm vascular study - Forearm blood flow will be measured using venous occlusion plethysmography at baseline and with each dose of Ucn 2, 3 and Substance P.
After a 20 minute infusion of intra arterial saline, healthy volunteers will receive ascending doses of intra arterial Urocortin 2 (3.4, 34 and 340 pmol/min to achieve estimated end-organ concentrations of 0.06, 0.6 and 6 µg/L, respectively), Urocortin 3 (3.4, 34 and 340 pmol/min to achieve estimated end-organ concentrations of 0.06, 0.6 and 6 µg/L, respectively) and Substance P (a control endothelium-dependent vasodilator that evokes endogenous t-PA release [2, 4 and 8 pmol/min]). This will be co-infused with either Astressin 2B (in one of the two doses determined from Protocol 1) or saline placebo.
Bilateral venous blood sampling will be performed at baseline, immediately before the start and after each dose of Urocortin 2 and 3, to later estimate net release of tPA and PAI-1 and for plasma measurements of Urocortins 2 and 3.
Saline placeboDrug
Also called Forearm vascular study - Bilateral forearm blood flow will be measured at baseline and after each dose of Ucn 2, 3 and Substance P.
After 20 minutes of intra arterial saline infusion, incremental doses of Urocortin 2, 3 and Substance P will be administered (in doses similar to Active comparator arm), co infused with saline placebo.
Bilateral venous blood samples will be taken at baseline, immediately before the start of Ucn2/Ucn3 infusion and at the end of each dose of Ucn2/Ucn3 for subsequent calculation of net release of t-PA and PAI-1.
| Study group | Role | What they receive |
|---|---|---|
| Saline Placebo | Placebo comparator | In this arm, the response in forearm blood flow to incremental doses of Urocortins 2, 3 and Substance P will be studied co infused with saline placebo. Receives: Drug: Saline placebo |
| Response to Urocortin infusion in presence of Astressin 2B | Active comparator | This arm studies the response to intra arterial infusion of incremental doses of Urocortins 2, 3 and Substance P in the presence or absence of a selective antagonist - Astressin 2B. Receives: Drug: Urocortin 2, Urocortin 3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Forearm blood flow
Difference between forearm blood flow in response to doses of Ucn2, Ucn3 and Substance P in the presence vs absence of Astressin 2B dose 1 and in the presence vs absence of Astressin 2B dose 2
Measured: 2.30 hours
Secondary outcomes (1)
Net t-PA release
Net t-PA release induced by Ucn2 and Ucn3 in the presence vs absence of Astressin 2B dose 1 and in the presence vs the absence of Astressin 2B dose 2.
Measured: 2.30 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2010 (estimated)
- Study startAug 2010
- Primary completionAug 2012
- Study completion31 Aug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Vascular DiseaseStudies of the same condition, open and under way.
- More trials run by University of EdinburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- NHS Lothian
- Responsible party
- Sponsor
- Investigators
- David E Newby, PhD FRCP, Principal investigator, University of Edinburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01096693
- Sponsor's protocol ID
- SV.Procotol 2
- Status last verified
- Apr 2024
- First submitted
- 30 Mar 2010
- Last updated
- 2 May 2024
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Urocortins on Forearm Arterial Blood Flow in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT01096693
- Acronym / sponsor ID
- SV.Procotol 2
- Conditions
- Vascular Disease, Heart Disease
- Keywords
- Urocortin 2, Urocortin 3, Astressin 2B, forearm blood flow, plethysmography, vascular, heart failure
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- NHS Lothian
- Study start
- Aug 2010 (actual)
- Primary completion
- Aug 2012 (actual)
- Study completion
- 31 Aug 2014 (actual)
- First posted
- 31 Mar 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Saline Placebo | Placebo comparator | Drug: Saline placeboIn this arm, the response in forearm blood flow to incremental doses of Urocortins 2, 3 and Substance P will be studied co infused with saline placebo. |
| Response to Urocortin infusion in presence of Astressin 2B | Active comparator | Drug: Urocortin 2, Urocortin 3This arm studies the response to intra arterial infusion of incremental doses of Urocortins 2, 3 and Substance P in the presence or absence of a selective antagonist - Astressin 2B. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Healthy male volunteers between 18 - 65 years (inclusive)
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Urocortin 2, Urocortin 3Also: Forearm vascular study - Forearm blood flow will be measured using venous occlusion plethysmography at baseline and with each dose of Ucn 2, 3 and Substance P.After a 20 minute infusion of intra arterial saline, healthy volunteers will receive ascending doses of intra arterial Urocortin 2 (3.4, 34 and 340 pmol/min to achieve estimated end-organ concentrations of 0.06, 0.6 and 6 µg/L, respectively), Urocortin 3 (3.4, 34 and 340 pmol/min to achieve estimated end-organ concentrations of 0.06, 0.6 and 6 µg/L, respectively) and Substance P (a control endothelium-dependent vasodilator that evokes endogenous t-PA release [2, 4 and 8 pmol/min]). This will be co-infused with either Astressin 2B (in one of the two doses determined from Protocol 1) or saline placebo. Bilateral venous blood sampling will be performed at baseline, immediately before the start and after each dose of Urocortin 2 and 3, to later estimate net release of tPA and PAI-1 and for plasma measurements of Urocortins 2 and 3. | Drug | Response to Urocortin infusion in presence of Astressin 2B |
| Saline placeboAlso: Forearm vascular study - Bilateral forearm blood flow will be measured at baseline and after each dose of Ucn 2, 3 and Substance P.After 20 minutes of intra arterial saline infusion, incremental doses of Urocortin 2, 3 and Substance P will be administered (in doses similar to Active comparator arm), co infused with saline placebo. Bilateral venous blood samples will be taken at baseline, immediately before the start of Ucn2/Ucn3 infusion and at the end of each dose of Ucn2/Ucn3 for subsequent calculation of net release of t-PA and PAI-1. | Drug | Saline Placebo |
Primary outcome
Forearm blood flow
Time frame: 2.30 hours
Difference between forearm blood flow in response to doses of Ucn2, Ucn3 and Substance P in the presence vs absence of Astressin 2B dose 1 and in the presence vs absence of Astressin 2B dose 2
1 secondary outcome
Net t-PA release
Time frame: 2.30 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 May 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David E Newby, PhD FRCP principal investigator
University of Edinburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Urocortin 2, Urocortin 3 in people with Vascular Disease and Heart Disease, run by University of Edinburgh at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Forearm blood flow (time frame: 2.30 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 May 2024.