- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02259686
Cardiovascular Effects of Apelin In Healthy Volunteers
Study Overview
Status
Conditions
Detailed Description
Study Protocols Groups of 5 subjects will be assigned to receive one of three protocols.
Protocol 1:
Five healthy volunteers will be asked to attend the clinical research facility on a total of 4 occasions as per the protocol below.
Visits 1 and 2 will occur over two consecutive days. Participants will attend at 07.30 and be given a light breakfast. An intravenous sampling cannula will be inserted into the antecubital vein of one arm. Blood samples (5 mL) will be taken immediately prior to subcutaneous injection (t=0; 08.00) of 1 mg (Pyr1)apelin-13 and at 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 600 min after injection. Subjects will then be discharged from the facility and reattend the following day at 08.00 for a single venous sample. Approximately 85 mL of blood will be sampled in total over this time.
Visits 3 and 4 will also occur over two consecutive days, at least one week after visit 2. Subjects will attend at 07.30 and be given a light breakfast. An intravenous sampling cannula will be inserted into the antecubital vein of one arm. Blood samples (5 mL) will be taken immediately prior to an intravenous bolus infusion (t=0; 08.00) of 1 mg (Pyr1)apelin-13 over 15 min and at 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 600 min after injection. Subjects will then be discharged from the facility and reattend the following day at 08.00 for a single venous sample.
Protocol 2:
Five healthy volunteers will be asked to attend the clinical research facility on a total of 4 occasions as per the protocol below.
Visits 1 and 2 will occur over two consecutive days. Participants will attend at 07.30 and be given a light breakfast. An intravenous sampling cannula will be inserted into the antecubital vein of one arm. Blood samples (5 mL) will be taken immediately prior to subcutaneous injection (t=0; 08.00) of 5 mg (Pyr1)apelin-13 and at 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 600 min after injection. Subjects will then be discharged from the facility and reattend the following day at 08.00 for a single venous sample. Approximately 85 mL of blood will be sampled in total over this time.
Visits 3 and 4 will also occur over two consecutive days, at least one week after visit 2. Subjects will attend at 07.30 and be given a light breakfast. An intravenous sampling cannula will be inserted into the antecubital vein of one arm. Blood samples (5 mL) will be taken immediately prior to an intravenous bolus infusion (t=0; 08.00) of 5 mg (Pyr1)apelin-13 over 15 min and at 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 600 min after injection. Subjects will then be discharged from the facility and reattend the following day at 08.00 for a single venous sample.
Protocol 3:
Five healthy volunteers will be asked to attend the clinical research facility for 2 consecutive days. Subjects will attend at 07.30 and be given a light breakfast. An intravenous sampling cannula will be inserted into the antecubital vein of one arm. Blood samples (5 mL) will be taken immediately prior to commencing a 24-h subcutaneous infusion of (t=0; 08.00) of 10 mg (Pyr1)apelin-13 dissolved in 10 mL water for injection. Further venous sampling will take place at 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 600 min after injection. Subjects will then be discharged from the facility and reattend the following day at 08.00 for a single venous sample.
Measurements
Thoracic Bioimpedance Cardiography By virtue of changes in transthoracic electrical impedance during cardiac ejection, thoracic bioimpedance cardiography allows the non-invasive assessment of cardiac stroke volume and the calculation of cardiac output and cardiac index. After skin preparation, four pairs of low-contact impedance 'sensing' and 'current injecting' electrodes will be attached to the patient and connected to an impedance cardiograph. This technique has been applied widely and compares favourably with both invasive and other non-invasive (echocardiographic) measures of cardiac output. These variables will therefore be recorded at regular intervals throughout the study in all 3 protocols. Heart rate and blood pressure will also be monitored at regular intervals throughout each study using a semi-automated oscillometric sphygmomanometer (Omron HEM-705CP, Omron, Matsusaka, Japan). Mean arterial pressure (MAP) will be calculated as diastolic blood pressure plus a third of the pulse pressure.
Assays Blood samples (5 mL) will be collected before and at the end of each drug infusion into ethylene diamine tetraacetic acid (EDTA), centrifuged and plasma frozen in three 1-mL aliquots to be stored at -80 °C until assay. Plasma concentrations of apelin will be measured by collaborators at Bristol Myers Squibb, Princeton, USA.
Methods of Statistical Analysis
Outcome data will be analysed where appropriate, by analysis of variance (ANOVA) with repeated measures, regression analysis, and paired and unpaired Student's t-test. Statistical significance will be taken at the 5% level.
Study Type
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
-
-
-
Edinburgh, United Kingdom, EH16 4SA
- Clinical Research Facility University of Edinburgh
-
Edinburgh, United Kingdom, EH4 2XU
- Wellcome Trust Clinical Research Facility. Western General Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Healthy males or females >18 years old
- Willing and able to complete an informed consent form
Exclusion Criteria:
- Unable to give informed consent
- Pregnant or lactating at screening
- Use of any investigation product or device within 30 days prior to study.
Study Plan
How is the study designed?
Design Details
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Protocol 1. Apelin 1mg doses
5 Healthy volunteers
|
single subcutaneous injection of Apelin 1mg subcutaneous
Other Names:
15 minute intravenous bolus of Apelin 1mg intravenous
Other Names:
|
Experimental: Protocol 2. Apelin 5mg doses
5 Healthy volunteers
|
single subcutaneous injection of Apelin 5mg subcutaneous
Other Names:
15 minute intravenous infusion of Apelin 5mg intravenous
Other Names:
|
Experimental: Protocol 3. Apelin 10mg single dose
5 Healthy volunteers
|
24 hour continuous subcutaneous infusion of Apelin 10 mg subcutaneous
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in cardiac output between different methods of apelin administration.
Time Frame: 10 hours
|
Difference in cardiac output between different treatment arms.
This will be assessed by recording cardiac index in L/min/m2 and Stroke volume index mL/min/m2
|
10 hours
|
Change in blood pressure between different methods of apelin administration.
Time Frame: 10 hours
|
Difference in blood pressure between different treatment arms assessed by measuring mean blood pressure in mmHg.
Mean arterial pressure (MAP) will be calculated as diastolic blood pressure plus a third of the pulse pressure
|
10 hours
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in apelin concentrations between the different methods of administration
Time Frame: 24 hours
|
Difference in temporal profile of apelin concentrations produced by different methods of apelin administration
|
24 hours
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: David Newby, British Heart Foundation
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- Apelin2014
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Healthy
-
Prevent Age Resort "Pervaya Liniya"RecruitingHealthy Aging | Healthy Diet | Healthy LifestyleRussian Federation
-
Maastricht University Medical CenterCompletedHealthy Volunteers | Healthy Subjects | Healthy AdultsNetherlands
-
Yale UniversityNot yet recruitingHealth-related Benefits of Introducing Table Olives Into the Diet of Young Adults: Olives For HealthHealthy Diet | Healthy Lifestyle | Healthy Nutrition | CholesterolUnited States
-
Hasselt UniversityRecruitingHealthy | Healthy AgingBelgium
-
Galera Therapeutics, Inc.Syneos HealthCompleted
-
Galera Therapeutics, Inc.Syneos HealthCompletedHealthy | Healthy VolunteersAustralia
-
University of PennsylvaniaActive, not recruitingHealthy | Healthy AgingUnited States
-
Chalmers University of TechnologyGöteborg UniversityCompletedHealthy | Nutrition, HealthySweden
-
University of ManitobaNot yet recruitingHealthy | Healthy Diet
Clinical Trials on Apelin 1mg subcutaneous
-
Ain Shams UniversityCompletedRecurrent Pregnancy LossEgypt
-
University Hospital, Basel, SwitzerlandRecruitingEffects of Intravenous [Pyr1]Apelin-13 on Healthy Volunteers With Artificially Induced SIAD (ESCAPE)Hyponatremia | SIAD - Syndrome of Inappropriate AntidiuresisSwitzerland
-
University Hospital, ToulouseSociété Francophone du DiabèteCompleted
-
Golden Jubilee National HospitalNHS Lothian; Imperial College Healthcare NHS TrustUnknownHeart Failure | Pulmonary Arterial HypertensionUnited Kingdom
-
University of CambridgeCompletedCardiovascular DiseaseUnited Kingdom
-
Cairo UniversityCompletedDiabetic NephropathiesEgypt
-
Imperial College LondonCompletedIdiopathic Pulmonary Arterial HypertensionUnited Kingdom
-
University Hospital, ToulouseCompleted
-
University of EdinburghUnknown
-
Chong Kun Dang PharmaceuticalCompleted