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

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ClinicalTrials.gov Identifier: NCT01417663
Recruitment Status : Completed
First Posted : August 16, 2011
Last Update Posted : September 9, 2013
Sponsor:
Collaborators:
Dutch Heart Foundation
Synvista Therapeutics, Inc
Information provided by (Responsible Party):
Maria Hopman, Radboud University

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.

Condition or disease Intervention/treatment Phase
Cardiovascular Disease Aging Endothelial Dysfunction Physical Activity Drug: Alt-711 Behavioral: Physical exercise training Phase 2 Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Combining Exercise Training With a Drug to Break AGE-crosslinks; Effects on Cardiovascular Structure and Function and Related Mechanisms
Study Start Date : November 2008
Actual Primary Completion Date : June 2011
Actual Study Completion Date : June 2011

Resource links provided by the National Library of Medicine


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

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




Primary Outcome Measures :
  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 Outcome Measures :
  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.




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Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01417663


Locations
Netherlands
Radboud University Nijmegen Medical Centre
Nijmegen, Netherlands, 6525EZ
Sponsors and Collaborators
Radboud University
Dutch Heart Foundation
Synvista Therapeutics, Inc
Investigators
Principal Investigator: Maria TE Hopman, MD, PhD Radboud University

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Maria Hopman, Prof.Dr. M.T.E. Hopman, Radboud University
ClinicalTrials.gov Identifier: NCT01417663     History of Changes
Other Study ID Numbers: ALT-711-0529B
First Posted: August 16, 2011    Key Record Dates
Last Update Posted: September 9, 2013
Last Verified: September 2013

Keywords provided by Maria Hopman, Radboud University:
Aging
Cardiovascular disease
Endothelial function
Physical activity
Advanced Glycation Endproducts
AGE crosslink breakers

Additional relevant MeSH terms:
Cardiovascular Diseases