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

Phase 2

Completed

• Conditions: Cardiovascular Disease; Aging; Endothelial Dysfunction; Physical Activity
• Interventions: Drug: Alt-711; Behavioral: Physical exercise training

• Registration Number: NCT01417663
• Lead Sponsor: Radboud University Medical Center

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2008-11
• Primary Completion: 2011-06
• Study Completion: 2011-06
• Study First Submitted: 2011-06-17
• Study First Submitted QC: 2011-08-15
• Study First Posted: 2011-08-16
• Status Verified: 2013-09
• Last Update Submitted: 2013-09-06
• Last Update Posted: 2013-09-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 48

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Alagebrium	Physical 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
Exercise training	Alt-711	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
Exercise training	Physical 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
Alagebrium	Alt-711	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

Primary Outcome Measures

Name	Time	Method
Examine the combined effects of one year exercise training and the AGE-crosslink breaker Alagebrium on vascular endothelial function.	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 Outcome Measures

Name	Time	Method
Examine the individual effects of one year exercise training and the AGE-crosslink breaker Alagebrium on vascular endothelial function.	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.
Examine the combined effects of one year exercise training and the AGE-crosslink breaker Alagebrium on cardiac function.	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.
Examine the individual effects of one year exercise training and the AGE-crosslink breaker Alagebrium on cardiac function.	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.
Examine the combined effects of one year exercise training and the AGE-crosslink breaker Alagebrium on cerebral perfusion and cognitive function.	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.
Examine the individual effects of one year exercise training and the AGE-crosslink breaker Alagebrium on cerebral perfusion and cognitive function.	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.

Trial Locations

Locations (1)

Radboud University Nijmegen Medical Centre; 🇳🇱 Nijmegen, Netherlands