HealthyEarly Phase 1NCT02259686
Cardiovascular Effects of Apelin In Healthy Volunteers
A Early Phase 1 study testing Apelin 1mg subcutaneous, Apelin 1mg intravenous and Apelin 5mg subcutaneous in people with Healthy, run by University of Edinburgh at 2 sites in United Kingdom.
Trial summary
Apelin is an endogenous peptide with physiological actions in the cardiovascular system. Apelin can modulate vasomotor tone and is a potent endogenous inotrope. In a series of clinical studies, we have shown that apelin causes peripheral and coronary vasodilatation and increased cardiac contractility. Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Apelin 1mg subcutaneous, Apelin 1mg intravenous and Apelin 5mg subcutaneous
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- Nov 2014to May 2015
- Phase
- Early Phase 1
- 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 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy males or females >18 years old
- Willing and able to complete an informed consent form
Who cannot join
- Unable to give informed consent
- Pregnant or lactating at screening
- Use of any investigation product or device within 30 days prior to study.
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
Clinical Research Facility University of Edinburgh
Edinburgh, EH16 4SA
Wellcome Trust Clinical Research Facility. Western General Hospital
Edinburgh, EH4 2XU
About this study
Apelin is an endogenous peptide with physiological actions in the cardiovascular system. Apelin can modulate vasomotor tone and is a potent endogenous inotrope. In a series of clinical studies, we have shown that apelin causes peripheral and coronary vasodilatation and increased cardiac contractility. We wish to study and compare the cardiovascular effects of subcutaneous versus intravenous apelin. We specifically wish to determine how different methods of apelin administration affect cardiac output and peripheral vascular resistance in healthy volunteers
Read the 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.
- Conditions
- Healthy
- Being tested
- Apelin 1mg subcutaneous, Apelin 1mg intravenous, Apelin 5mg subcutaneous, Apelin 5mg intravenous, Apelin 10 mg subcutaneous
- Keywords
- Apelin, volunteers
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Apelin 1mg subcutaneousDrug
Also called 1mg Sc
single subcutaneous injection of Apelin 1mg subcutaneous
Apelin 1mg intravenousDrug
Also called 1mg iv
15 minute intravenous bolus of Apelin 1mg intravenous
Apelin 5mg subcutaneousDrug
Also called 5mg Sc
single subcutaneous injection of Apelin 5mg subcutaneous
Apelin 5mg intravenousDrug
Also called 5mg iv
15 minute intravenous infusion of Apelin 5mg intravenous
Apelin 10 mg subcutaneousDrug
Also called 10mg sc
24 hour continuous subcutaneous infusion of Apelin 10 mg subcutaneous
| Study group | Role | What they receive |
|---|---|---|
| Protocol 1. Apelin 1mg doses | Experimental | 5 Healthy volunteers Receives: Drug: Apelin 1mg subcutaneous; Drug: Apelin 1mg intravenous |
| Protocol 2. Apelin 5mg doses | Experimental | 5 Healthy volunteers Receives: Drug: Apelin 5mg subcutaneous; Drug: Apelin 5mg intravenous |
| Protocol 3. Apelin 10mg single dose | Experimental | 5 Healthy volunteers Receives: Drug: Apelin 10 mg subcutaneous |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in cardiac output between different methods of apelin administration.
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
Measured: 10 hours
Change in blood pressure between different methods of apelin administration.
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
Measured: 10 hours
Secondary outcomes (1)
Change in apelin concentrations between the different methods of administration
Difference in temporal profile of apelin concentrations produced by different methods of apelin administration
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2014 (estimated)
- Study startNov 2014
- Primary completionMay 2015
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies 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
- Early Phase 1
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- NHS Lothian
- Responsible party
- Sponsor
- Investigators
- David Newby, Principal investigator, British Heart Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02259686
- Sponsor's protocol ID
- Apelin2014
- Status last verified
- May 2015
- First submitted
- 1 Oct 2014
- Last updated
- 1 Jun 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiovascular Effects of Apelin In Healthy Volunteers
- ClinicalTrials.gov ID
- NCT02259686
- Acronym / sponsor ID
- Apelin2014
- Conditions
- Healthy
- Keywords
- Apelin, volunteers
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- NHS Lothian
- Study start
- Nov 2014
- Primary completion
- May 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 8 Oct 2014 (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.
Apelin is an endogenous peptide with physiological actions in the cardiovascular system. Apelin can modulate vasomotor tone and is a potent endogenous inotrope. In a series of clinical studies, we have shown that apelin causes peripheral and coronary vasodilatation and increased cardiac contractility. We wish to study and compare the cardiovascular effects of subcutaneous versus intravenous apelin. We specifically wish to determine how different methods of apelin administration affect cardiac output and peripheral vascular resistance in healthy volunteers
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 design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Protocol 1. Apelin 1mg doses | Experimental | Drug: Apelin 1mg subcutaneous, Drug: Apelin 1mg intravenous5 Healthy volunteers |
| Protocol 2. Apelin 5mg doses | Experimental | Drug: Apelin 5mg subcutaneous, Drug: Apelin 5mg intravenous5 Healthy volunteers |
| Protocol 3. Apelin 10mg single dose | Experimental | Drug: Apelin 10 mg subcutaneous5 Healthy volunteers |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Healthy males or females >18 years old
- Willing and able to complete an informed consent form
Key exclusion criteria (3 listed)
- Unable to give informed consent
- Pregnant or lactating at screening
- Use of any investigation product or device within 30 days prior to study.
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 |
|---|---|---|
| Apelin 1mg subcutaneousAlso: 1mg Scsingle subcutaneous injection of Apelin 1mg subcutaneous | Drug | Protocol 1. Apelin 1mg doses |
| Apelin 1mg intravenousAlso: 1mg iv15 minute intravenous bolus of Apelin 1mg intravenous | Drug | Protocol 1. Apelin 1mg doses |
| Apelin 5mg subcutaneousAlso: 5mg Scsingle subcutaneous injection of Apelin 5mg subcutaneous | Drug | Protocol 2. Apelin 5mg doses |
| Apelin 5mg intravenousAlso: 5mg iv15 minute intravenous infusion of Apelin 5mg intravenous | Drug | Protocol 2. Apelin 5mg doses |
| Apelin 10 mg subcutaneousAlso: 10mg sc24 hour continuous subcutaneous infusion of Apelin 10 mg subcutaneous | Drug | Protocol 3. Apelin 10mg single dose |
Primary outcome
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
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
1 secondary outcome
Change in apelin concentrations between the different methods of administration
Time frame: 24 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 1 Jun 2015.
Related trials for Healthy
Recruiting
THE EFFECTS OF GAME-BASED EXERCISE PROGRAMS
Physical Activity, Body Image
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
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 Newby principal investigator
British Heart Foundation
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Apelin 1mg subcutaneous, Apelin 1mg intravenous and Apelin 5mg subcutaneous in people with Healthy, run by University of Edinburgh at 2 sites 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 2 inclusion and 3 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 1 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Change in cardiac output between different methods of apelin administration. (time frame: 10 hours). The study lists 2 primary outcomes in all. 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 1 Jun 2015.