Cardiac Energetics and Function in Normal Human Ageing

Ageing Clinical Trial

Official title:

Cardiac Energetics and Function in Normal Human Ageing

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01504828
• Other study ID #: BH111454
• Secondary ID: 95309
• Status: Completed
• Phase: N/A
• First received: December 21, 2011
• Last updated: March 29, 2017
• Start date: July 2012
• Est. completion date: December 2015

Study information

• Verified date: March 2017
• Source: Newcastle-upon-Tyne Hospitals NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 135
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Ageing
• Left Ventricular Function Diastolic Dysfunction
• Left Ventricular Function Systolic Dysfunction

Intervention

Drug:
• Ramipril
Ramipril in one dose to reduce vascular stiffness to determine effects of this on left ventricular function and energetics

Locations

Country	Name	City	State
United Kingdom	Campus for Ageing and Vitality	Newcastle upon Tyne

Sponsors (1)

Lead Sponsor	Collaborator
Newcastle-upon-Tyne Hospitals NHS Trust

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

Hollingsworth KG, Blamire AM, Keavney BD, Macgowan GA. Left ventricular torsion, energetics, and diastolic function in normal human aging. Am J Physiol Heart Circ Physiol. 2012 Feb 15;302(4):H885-92. doi: 10.1152/ajpheart.00985.2011. Epub 2011 Dec 16. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Vascular Stiffness	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).	2 Hours - Acute study with no follow-up
Primary	Left Ventricular Energetics	Left ventricular energetics is measured as the ratio of phosphocreatine to adenosine triphosphate	2 hours - Acute Study, no follow-up
Primary	Left Ventricular Function	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.	2 hours - Acute Study, no follow-up
Secondary	Effects of ACE inhibitor on left ventricular energetics and function in those subjects aged 40 and over	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.	6 hours - Acute study, no follow-up