Effects of Exercise Training and AGE-crosslink Breaker on Cardiovascular Structure and Function

September 6, 2013 updated by: Maria Hopman, Radboud University Medical Center

Combining Exercise Training With a Drug to Break AGE-crosslinks; Effects on Cardiovascular Structure and Function and Related Mechanisms

Healthy but sedentary aging leads to increased morbidity and mortality of cardiovascular disease. This is partly due to the accumulation of Advanced Glycation Endproducts (AGEs) and the stiffening of the myocardium and arteries. New medication has been developed to break these AGE-crosslinks to improve cardiovascular compliance. The positive influence of regular physical activity is well known for cardiovascular disease and aging. Therefore, what is the most effective intervention, physical exercise and/or new medication AGE-crosslink breakers, in improving the cardiovascular and cerebrovascular compliance and improving the endothelial function in healthy sedentary elderly.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

48

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Nijmegen, Netherlands, 6525EZ
        • Radboud University Nijmegen Medical Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

65 years and older (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Healthy sedentary elderly
  • Age 65 yrs and older

Exclusion Criteria:

  • Cardiovascular disease
  • Cerebrovascular disease
  • Changes on ECG indicating cardiomyopathy or ischemia
  • No cardiovascular medication
  • Diabetes Mellitus
  • Hypercholesterolemia
  • BMI > 33 kg/m2
  • Intensive exercise > 1 hour a week

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Alagebrium

In this study there will be four different groups:

One Alagebrium 100 mg twice daily and exercise training 3x/week Two Placebo twice daily and exercise training 3x/week Three Alagebrium 100 mg twice daily and no exercise training Four Placebo twice daily and no exercise training
Drug: Alt-711
Alt-711, also known as Alagebrium, an AGE-crosslink breaker, will be given twice daily 100mg
Other Names:
  • AGE crosslink breaker
  • Alagebrium
  • 4,5-dimethyl-3-(2-oxo-2-phenylethyl)-thiazolium chloride
Behavioral: Physical exercise training
Exercise training will be given three times a week for 45 minutes per training session. The heart rate reserve will be slowly increased from 70% to 85%.
Other Names:
  • Exercise training
  • Cardiopulmonary fitness training
  • Cycloergometer
Other: Exercise training

In this study there will be four different groups:

One Alagebrium 100 mg twice daily and exercise training 3x/week Two Placebo twice daily and exercise training 3x/week Three Alagebrium 100 mg twice daily and no exercise training Four Placebo twice daily and no exercise training
Drug: Alt-711
Alt-711, also known as Alagebrium, an AGE-crosslink breaker, will be given twice daily 100mg
Other Names:
  • AGE crosslink breaker
  • Alagebrium
  • 4,5-dimethyl-3-(2-oxo-2-phenylethyl)-thiazolium chloride
Behavioral: Physical exercise training
Exercise training will be given three times a week for 45 minutes per training session. The heart rate reserve will be slowly increased from 70% to 85%.
Other Names:
  • Exercise training
  • Cardiopulmonary fitness training
  • Cycloergometer

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Examine the combined effects of one year exercise training and the AGE-crosslink breaker Alagebrium on vascular endothelial function.
Time Frame: 0 and 12 months
At baseline and 12 months the endothelial function will be measured with an invasive vascular function measurement using the leg model. Via an arterial line in the common femoral artery acethylcholine, sodium nitroprusside and LNMMA will be infused at different dosages. Vascular response will be measured using venous occlusion plethysmography. Non-invasive vascular measurements, e.g.flow mediated dilation and pulse wave velocity, using ultrasound techniques will be performed at 0, 6 and 12 months. Also, cardiopulmonary fitness level will be tested at 0, 3, 6 and 12 months with an ergometer.
0 and 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Examine the individual effects of one year exercise training and the AGE-crosslink breaker Alagebrium on vascular endothelial function.
Time Frame: 0 and 12 months
At baseline and 12 months the endothelial function will be measured with an invasive vascular function measurement using the leg model. Via an arterial line in the common femoral artery acethylcholine, sodium nitroprusside and LNMMA will be infused at different dosages. Vascular response will be measured using venous occlusion plethysmography. Non-invasive vascular measurements, e.g.flow mediated dilation and pulse wave velocity, using ultrasound techniques will be performed at 0, 6 and 12 months. Also, cardiopulmonary fitness level will be tested at 0, 3, 6 and 12 months with an ergometer.
0 and 12 months
Examine the combined effects of one year exercise training and the AGE-crosslink breaker Alagebrium on cardiac function.
Time Frame: 0, 6 and 12 months
An echocardiogram will be performed at baseline, 6 and 12 months. Measures such as strain, strain rate and myocardial velocity, together with the diastolic function parameters (e.g. E/A, S/D, and E/E' ratio) will be specifically evaluated. Also, the common measures such as wall thickness, volumes, etc, will be examined.
0, 6 and 12 months
Examine the individual effects of one year exercise training and the AGE-crosslink breaker Alagebrium on cardiac function.
Time Frame: 0, 6 and 12 months
An echocardiogram will be performed at baseline, 6 and 12 months. Measures such as strain, strain rate and myocardial velocity, together with the diastolic function parameters (e.g. E/A, S/D, and E/E' ratio) will be specifically evaluated. Also, the common measures such as wall thickness, volumes, etc, will be examined.
0, 6 and 12 months
Examine the combined effects of one year exercise training and the AGE-crosslink breaker Alagebrium on cerebral perfusion and cognitive function.
Time Frame: 0 and 12 months

A cerebral perfusion measurement will be performed at baseline and after 12 months with transcranial doppler, near infra-red spectroscopy and continuous beat to beat blood pressure monitoring using the Finameter during different posture maneuvers and hypo- and hypercapnia. Dynamic cerebral autoregulation and vasoreactivity will be examined.

Cognitive function will be measured at baseline, 6 and 12 months using the CANTAB.
0 and 12 months
Examine the individual effects of one year exercise training and the AGE-crosslink breaker Alagebrium on cerebral perfusion and cognitive function.
Time Frame: 0 and 12 months

A cerebral perfusion measurement will be performed at baseline and after 12 months with transcranial doppler, near infra-red spectroscopy and continuous beat to beat blood pressure monitoring using the Finameter during different posture maneuvers and hypo- and hypercapnia. Dynamic cerebral autoregulation and vasoreactivity will be examined.

Cognitive function will be measured at baseline, 6 and 12 months using the CANTAB.
0 and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Collaborators

Dutch Heart Foundation
Synvista Therapeutics, Inc

Investigators

  • Principal Investigator: Maria TE Hopman, MD, PhD, Radboud University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2008

Primary Completion (Actual)

June 1, 2011

Study Completion (Actual)

June 1, 2011

Study Registration Dates

First Submitted

June 17, 2011

First Submitted That Met QC Criteria

August 15, 2011

First Posted (Estimate)

August 16, 2011

Study Record Updates

Last Update Posted (Estimate)

September 9, 2013

Last Update Submitted That Met QC Criteria

September 6, 2013

Last Verified

September 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ALT-711-0529B

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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