Cardiac Energetics and Function in Normal Human Ageing

Sponsor

Newcastle-upon-Tyne Hospitals NHS Trust (Other)

Overall Status

Completed

CT.gov ID

NCT01504828

Collaborator

(none)

135

Enrollment

Location

Arm

Duration (Months)

3.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Left Ventricular Function Systolic Dysfunction Left Ventricular Function Diastolic Dysfunction Ageing	Drug: Ramipril	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

135 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Cardiac Energetics and Function in Normal Human Ageing

Study Start Date :

Jul 1, 2012

Actual Primary Completion Date :

Dec 1, 2015

Actual Study Completion Date :

Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Vascular Stiffness [2 Hours - Acute study with no follow-up]
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 [2 hours - Acute Study, no follow-up]
Left ventricular energetics is measured as the ratio of phosphocreatine to adenosine triphosphate
Left Ventricular Function [2 hours - Acute Study, no follow-up]
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 [6 hours - Acute study, no follow-up]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.