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Completed

NCT Number: NCT01417663

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

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.

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Key information

Conditions

Cardiovascular Disease Aging Behavior Cardiovascular Diseases Endothelial Dysfunction Motor Activity Physical Activity

Age range

65 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Radboud University Nijmegen Medical Centre

Nijmegen, 6525EZ, Netherlands

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Alt-711

Drug

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

Physical exercise training

Behavioral

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

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

Sponsors and collaborators

Lead sponsor

Radboud University Medical Center

Other

Collaborators

  • Dutch Heart Foundation
  • Synvista Therapeutics, Inc

Registry information

Official study title

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

Important dates

Study start
2008
Primary completion
2011
Study completion
2011
First posted
Aug 16, 2011
Registry last updated
Sep 9, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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