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| Name | Class |
|---|---|
| NHS Lothian | OTHER_GOV |
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Despite modern advances in treatment, heart failure continues to carry a poor prognosis with high morbidity and mortality rates. Hence, there remains a major interest in the development of novel therapeutic agents for this debilitating condition. Urocortins have recently shot into limelight with their potential role in the pathophysiology and treatment of heart failure.
Recent studies by the investigators group (REC no: 09/S1103/41) have confirmed that Urocortin 2 and 3 are potent arterial vasodilators, the effects of which are reproducible and well tolerated in healthy male volunteers. Previous studies using heart failure models in animals1-7, as well studies in heart failure patients (Urocortin 2), suggest that there is great scope for Urocortins as novel biomarkers and as potential therapeutic agents in heart failure. With this in mind, the investigators wish to study the local vasomotor effects of these peptides in greater detail in patients with heart failure.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients with heart failure | Other | Assessing the response to infusion of intra-arterial Urocortin 2, 3 and Substance P in patients with heart failure |
|
| Healthy controls | Other | Assessing response to intra-arterial infusions of Urocortin 2, 3 and Substance P in age and sex-matched healthy volunteers as controls. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Urocortin 2, Urocortin 3 and Substance P | Drug | After a 20-min infusion of intra-arterial saline, ascending doses of Urocortin 2 (3.6, 12 and 36 pmol/min [15, 50 and 150 ng/min] to achieve estimated end-organ concentrations of 0.6, 2 and 6 µg/L, respectively), Urocortin 3 1200, 3600 and 12000 pmol/min (5, 15 and 50 micrograms/min) [to achieve estimated end-organ concentrations of 199, 600 and 2000 micrograms/L respectively] and substance P (a control endothelium-dependent vasodilator that evokes endogenous t-PA release [2, 4 and 8 pmol/min]) will be administered intra-arterially. Baseline blood samples will be taken at the start of the study for full blood count, cholesterol, glucose, renal function 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 measurement of plasma Ucn 2 and 3 concentrations and other hormones. |
| Measure | Description | Time Frame |
|---|---|---|
| Forearm blood flow | Difference between forearm blood flow in response to doses of Ucn2, Ucn3 and Substance P between heart failure patients and healthy controls. | 3 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Absolute forearm blood flow | Absolute forearm arterial blood flow in response to Ucn2, Ucn3 and Substance P. | 3 hours |
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Inclusion Criteria:
Patients with heart failure:
Healthy volunteers:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David E Newby, PhD, FRCP | University of Edinburgh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Wellcome Trust Clinical Research Facility, Royal Infirmary of Edinburgh | Edinburgh | EH16 4SA | United Kingdom |
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| ID | Term |
|---|---|
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D054832 | Urocortins |
| D013373 | Substance P |
| ID | Term |
|---|---|
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D009479 | Neuropeptides |
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|
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D015320 | Tachykinins |
| D007705 | Kinins |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D009842 | Oligopeptides |
| D011506 | Proteins |
| D009419 | Nerve Tissue Proteins |
| D012898 | Autacoids |
| D018836 | Inflammation Mediators |
| D001685 | Biological Factors |