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

Aging Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01417663
• Other study ID #: ALT-711-0529B
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: June 17, 2011
• Last updated: September 6, 2013
• Start date: November 2008
• Est. completion date: June 2011

Study information

• Verified date: September 2013
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: June 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 65 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aging
• Cardiovascular Disease
• Cardiovascular Diseases
• Endothelial Dysfunction
• Physical Activity

Intervention

Drug:
• Alt-711
Alt-711, also known as Alagebrium, an AGE-crosslink breaker, will be given twice daily 100mg

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%.

Locations

Country	Name	City	State
Netherlands	Radboud University Nijmegen Medical Centre	Nijmegen

Sponsors (3)

Lead Sponsor	Collaborator
Radboud University	Dutch Heart Foundation, Synvista Therapeutics, Inc

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Examine the combined effects of one year exercise training and the AGE-crosslink breaker Alagebrium on vascular endothelial function.	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	Examine the individual effects of one year exercise training and the AGE-crosslink breaker Alagebrium on vascular endothelial function.	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	Examine the combined effects of one year exercise training and the AGE-crosslink breaker Alagebrium on cardiac function.	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
Secondary	Examine the individual effects of one year exercise training and the AGE-crosslink breaker Alagebrium on cardiac function.	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
Secondary	Examine the combined effects of one year exercise training and the AGE-crosslink breaker Alagebrium on cerebral perfusion and cognitive function.	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
Secondary	Examine the individual effects of one year exercise training and the AGE-crosslink breaker Alagebrium on cerebral perfusion and cognitive function.	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