Combining Exercise Training With a Drug to Break AGE-crosslinks; Effects on Cardiovascular Structure and Function and Related Mechanisms
Overview
- Phase
- Phase 2
- Intervention
- Alt-711
- Conditions
- Cardiovascular Disease
- Sponsor
- Radboud University Medical Center
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- Examine the combined effects of one year exercise training and the AGE-crosslink breaker Alagebrium on vascular endothelial function.
- Status
- Completed
- Last Updated
- 12 years ago
Overview
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.
Investigators
Maria Hopman
Prof.Dr. M.T.E. Hopman
Radboud University Medical Center
Eligibility Criteria
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
Arms & Interventions
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
Intervention: Alt-711
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
Intervention: Physical exercise training
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
Intervention: Alt-711
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
Intervention: Physical exercise training
Outcomes
Primary Outcomes
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
- Examine the individual effects of one year exercise training and the AGE-crosslink breaker Alagebrium on vascular endothelial function.(0 and 12 months)
- Examine the combined effects of one year exercise training and the AGE-crosslink breaker Alagebrium on cardiac function.(0, 6 and 12 months)
- Examine the individual effects of one year exercise training and the AGE-crosslink breaker Alagebrium on cardiac function.(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.(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.(0 and 12 months)