Cardiac Energetics and Function in Normal Human Ageing

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2012 by Newcastle-upon-Tyne Hospitals NHS Trust
Sponsor:
Information provided by (Responsible Party):
Guy A. MacGowan, Newcastle-upon-Tyne Hospitals NHS Trust
ClinicalTrials.gov Identifier:
NCT01504828
First received: December 21, 2011
Last updated: January 3, 2012
Last verified: January 2012
  Purpose

Normal aging is characterized by altered cardiovascular function. Our preliminary data with MR imaging and spectroscopy in normal subjects without cardiovascular disease or hypertension show that age-related cardiac dysfunction is characterized initially by impaired relaxation of the heart (40 - 60 years), and then at > 60 years altered contraction and impaired myocardial energetics. For the first time, the investigators will test whether the functional and energetic effects of normal aging can be reversed by acutely reducing stiffness of peripheral blood vessels using an ACE inhibitor. This will potentially have important insights into how normal aging affects the heart, and how potential treatments could be used to attenuate this process.


Condition Intervention
Left Ventricular Function Systolic Dysfunction
Left Ventricular Function Diastolic Dysfunction
Ageing
Drug: Ramipril

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Cardiac Energetics and Function in Normal Human Ageing

Resource links provided by NLM:


Further study details as provided by Newcastle-upon-Tyne Hospitals NHS Trust:

Primary Outcome Measures:
  • Vascular Stiffness [ Time Frame: 2 Hours - Acute study with no follow-up ] [ Designated as safety issue: No ]
    There are 3 principal measures of vascular stiffness, and these are central pulse pressure, central systolic pressure, and the augmentation index. These are correlated against the 3 principal measures of left ventricular function and energetics that are known to change with age: torsion to shortening ratio, early to late diastolic filling ratio, and the ratio of phosphocreatine to adenosine triphosphate (listed as separate Primary Outcome Measures).

  • Left Ventricular Energetics [ Time Frame: 2 hours - Acute Study, no follow-up ] [ Designated as safety issue: No ]
    Left ventricular energetics is measured as the ratio of phosphocreatine to adenosine triphosphate

  • Left Ventricular Function [ Time Frame: 2 hours - Acute Study, no follow-up ] [ Designated as safety issue: No ]
    Left ventricular function is measured with the 2 parameters that are known to change with age: ratio of early to late diastolic filling, and ratio of torsion to shortening ratio.


Secondary Outcome Measures:
  • Effects of ACE inhibitor on left ventricular energetics and function in those subjects aged 40 and over [ Time Frame: 6 hours - Acute study, no follow-up ] [ Designated as safety issue: No ]
    A single dose of ACE inhibitor is given to reduce vascular stiffness, and we then measure the effects of this on the measures of left ventricular function and energetics which are the torsion to shortening ratio, diastolic early to late filling ratio, and the phosphocreatine to adenosine triphosphate ratio.


Estimated Enrollment: 96
Study Start Date: July 2012
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ramipril
Those who are 40 years and older receive an ACE inhibitor to determine if this reduces age-related changes in left ventricular energetics and function
Drug: Ramipril
Ramipril in one dose to reduce vascular stiffness to determine effects of this on left ventricular function and energetics

Detailed Description:

Normal aging is characterized by altered cardiovascular function. Our preliminary data with MR imaging and spectroscopy in normal subjects without cardiovascular disease or hypertension show that age-related cardiac dysfunction is characterized initially by diastolic dysfunction (40 - 60 years), and then at > 60 years altered systolic strains and impaired myocardial energetics. The investigators propose to study the mechanism of these findings in subjects with normal aging without any cardiovascular disease, hypothesizing that increased vascular stiffening contributes to impaired energetics and left ventricular function. For the first time, the investigators will test whether the functional and energetic effects of normal aging can be reversed by acutely reducing afterload using an ACE inhibitor. This will be tested at 2 ages (40-60 and > 60 years), so that the intervention tests the hypothesis soon after the abnormalities develop (40-60 years - diastolic dysfunction; > 60 years energetics and altered strains). This will potentially have important insights into how normal aging affects the heart, and how potential treatments could be used to attenuate this process.

  Eligibility

Ages Eligible for Study:   20 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male and female subjects between the ages of 20 and 80 years

Exclusion Criteria:

  • Any cardiovascular condition including hypertension, or on any cardiovascular therapy.
  • Blood Pressure > 150 mmHg systolic, and/or > 90 mmHg diastolic
  • Claustrophobia
  • Implanted metal prosthesis
  • Chronic renal failure requiring dialysis
  • Diabetes mellitus.
  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: NCT01504828

Contacts
Contact: Guy A MacGowan, MD guy.macgowan@nuth.nhs.uk

Locations
United Kingdom
Campus for Ageing and Vitality Not yet recruiting
Newcastle upon Tyne, United Kingdom, NE4 6BE
Contact: Guy A MacGowan, MD       guy.macgowan@nuth.nhs.uk   
Sponsors and Collaborators
Newcastle-upon-Tyne Hospitals NHS Trust
Investigators
Principal Investigator: Guy A MacGowan, MD Freeman Hospital, Newcastle upon Tyne and Newcastle University
  More Information

Publications:
Responsible Party: Guy A. MacGowan, Consultant Cardiologist with Major Interest in Heart Failure, Honorary Clinical Senior Lecturer, Newcastle-upon-Tyne Hospitals NHS Trust
ClinicalTrials.gov Identifier: NCT01504828     History of Changes
Other Study ID Numbers: BH111454, 95309
Study First Received: December 21, 2011
Last Updated: January 3, 2012
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by Newcastle-upon-Tyne Hospitals NHS Trust:
Energy Metabolism
Ageing
left ventricle
energetics
function

Additional relevant MeSH terms:
Ramipril
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014