Haemodynamic Effects of Apelin Agonists and Antagonists in Man in COPD With Raised Pulmonary Artery Pressures

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2014 by Cambridge University Hospitals NHS Foundation Trust
Sponsor:
Collaborators:
Wellcome Trust
University of Cambridge
Information provided by (Responsible Party):
Joseph Cheriyan, MD, Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT02129309
First received: April 28, 2014
Last updated: April 30, 2014
Last verified: April 2014
  Purpose

The investigators are interested in studying how Pulmonary Hypertension occurs. A substance called 'apelin', that naturally occurs in the body has been shown to have an important role in heart disease. Previous studies have shown that it can make blood vessels get wider, and help blood flow around the body and thus improve the way the heart and lungs work.

The investigators are looking to recruit both healthy and COPD pulmonary hypertension patients to study 3 types of apelin. The purpose of this study is to help the investigators understand how Pulmonary Hypertension occurs which may will help with the development of future treatments.


Condition Intervention
COPD
Pulmonary Hypertension
Procedure: Forearm plethysmography
Procedure: Haemodynamic studies

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Prevention
Official Title: Haemodynamic Effects of Apelin Agonists and Antagonists in Man in COPD With Raised Pulmonary Artery Pressures.

Resource links provided by NLM:


Further study details as provided by Cambridge University Hospitals NHS Foundation Trust:

Primary Outcome Measures:
  • Percentage change in forearm blood flow in the infused arm. Forearm blood flow ratio in each arm, blood pressure and heart rate will also be reported. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Cardiac output and stroke volume, pulmonary vascular resistance, mean arterial pressure and heart rate. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Exploratory endpoints in Study 2 are systolic and diastolic blood pressure. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 72
Study Start Date: June 2014
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Systemic Apelin infusion

Study 2a - Haemodynamic studies to investigate the response to systemic infusions of 3 apelin agonists in healthy volunteers

Study 2b - Haemodynamic studies to investigate the response to 3 apelin agonists in COPD patients with elevated pulmonary artery pressures

Procedure: Haemodynamic studies
Dose response study
Other Names:
  • Innocor
  • Bioimpedance
  • Echocardiography
Experimental: Apelin infusion - forearm

Study 1a - A validation dose study of 3 apelin agonists using forearm plethysmography to evaluate changes in forearm blood flow: performed in healthy volunteers and COPD patients with elevated pulmonary artery pressures.

Study 1b- A validation dose study of apelin receptor antagonist using forearm plethysmography to evaluate changes in forearm blood flow, in healthy volunteers and COPD patients with elevated pulmonary artery pressures.

Procedure: Forearm plethysmography
Dose response study

Detailed Description:

The purpose of this study:

To investigate the physiological role of apelin in the cardiovascular system in patients with COPD with raised pulmonary artery pressures.

Study Aim and hypotheses:

The primary objective is to test the above hypotheses using forearm blood flow and systemic infusions of apelin peptides.

Hypotheses:

  1. Apelin agonists are vasodilators in human resistance vessels and this effect will be altered in patients with pulmonary hypertension.
  2. Apelin peptides improve right ventricular and pulmonary haemodynamics in patients with elevated pulmonary artery pressures.

Study 1a - A validation dose study of 3 apelin agonists performed in healthy volunteers and COPD patients with elevated pulmonary artery pressures.

Study 1b- A validation dose study of apelin receptor antagonist, in healthy volunteers and COPD patients with elevated pulmonary artery pressures.

Study 2a - To define the haemodynamic response to apelin agonists in healthy volunteers and evaluate the response.

Study 2b - To investigate the haemodynamic response to 3 apelin agonists in COPD patients with elevated pulmonary artery pressures.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy volunteers

    • Aged 18 to 70 years
    • Non-smoker (<1 cigarette per week)
    • If female, postmenopausal or on days 2-9 of menstrual cycle and negative pregnancy test COPD patients with estimated Pulmonary Artery Pressure (PAP) on echo >25mmHg
    • Clinical diagnosis of COPD as per standard criteria
    • Between 18 and 70 years
    • If female, postmenopausal or on days 2-9 of menstrual cycle and negative pregnancy test

Exclusion Criteria:

  • pre-existing:

    • Systemic Hypertension (sustained BP >160/100mmHg)
    • Ischaemic Heart Disease
    • Primary valvular heart disease
    • Significant left ventricular failure
    • Active malignancy
    • Renal disease (Creatinine >180 µmol/L)
    • Neurological disease
    • Diabetes mellitus
    • BMI >35, BMI <17
    • Pregnancy
    • Use of vasoactive medication or NSAIDS/aspirin within 48 hours of study.
    • Current involvement in other research studies, other than observational/non-interventional
    • Known HIV
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02129309

Contacts
Contact: Dr. Aimee Brame, MD MRCP 01223 296186 alb82@medschl.cam.ac.uk

Locations
United Kingdom
Vascular Research Unit, Clinical Pharmacology Unit, ACCI, Level 3, Addenbrooke's Hospital, Hills Road Not yet recruiting
Cambridge, United Kingdom, CB2 0QQ
Contact: Dr. Aimee Brame, MD    01223 296186    alb82@medschl.cam.ac.uk   
Principal Investigator: Dr Joseph Cheriyan, MD         
Sub-Investigator: Dr Carmel McEniery, PhD         
Sub-Investigator: Prof. Ian Wilkinson, DM FRCP         
Sub-Investigator: Dr. Anthony Davenport, MA         
Principal Investigator: Dr Aimee Brame, MD MRCP         
Sponsors and Collaborators
Cambridge University Hospitals NHS Foundation Trust
Wellcome Trust
University of Cambridge
Investigators
Principal Investigator: Dr. Joseph Cheriyan, MD Cambridge University Hospitals NHS Foundation Trust
  More Information

No publications provided

Responsible Party: Joseph Cheriyan, MD, Consultant Physician & Clinical Pharmacologist, Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT02129309     History of Changes
Other Study ID Numbers: ALPHa-COPD
Study First Received: April 28, 2014
Last Updated: April 30, 2014
Health Authority: United Kingdom: Cambridge University Hospitals NHS Foundation Trust

Keywords provided by Cambridge University Hospitals NHS Foundation Trust:
COPD
Apelin
agonist
antagonist

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 18, 2014