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

This study has been completed.
Sponsor:
Collaborators:
Dutch Heart Foundation
Synvista Therapeutics, Inc
Information provided by (Responsible Party):
Maria Hopman, Radboud University
ClinicalTrials.gov Identifier:
NCT01417663
First received: June 17, 2011
Last updated: September 6, 2013
Last verified: September 2013
  Purpose

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 Intervention Phase
Cardiovascular Disease
Aging
Endothelial Dysfunction
Physical Activity
Drug: Alt-711
Behavioral: Physical exercise training
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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:
  • 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 ] [ Designated as safety issue: No ]
    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. [ Time Frame: 0, 6 and 12 months ] [ Designated as safety issue: No ]
    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. [ Time Frame: 0, 6 and 12 months ] [ Designated as safety issue: No ]
    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. [ Time Frame: 0 and 12 months ] [ Designated as safety issue: No ]

    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. [ Time Frame: 0 and 12 months ] [ Designated as safety issue: No ]

    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.



Enrollment: 48
Study Start Date: November 2008
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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
  More Information

No publications provided by Radboud University

Additional 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
Study First Received: June 17, 2011
Last Updated: September 6, 2013
Health Authority: Netherlands: Medical Ethics Review Committee (METC)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
European Union: European Medicines Agency
United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Cardiovascular Diseases

ClinicalTrials.gov processed this record on August 18, 2014