The Effect of Exercise and Alagebrium on the Diastolic Function of the Heart (AGE)

August 4, 2020 updated by: Benjamin Levine, University of Texas Southwestern Medical Center
The purpose of this study is to determine whether an investigational drug (Alagebrium (generic: ALT-711), a type of medication referred to as an advanced glycaton end-product clever) can be combined with exercise training to reverse the stiffening of the heart that takes place naturally with aging.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Objectives: Chronic physical inactivity contributes to the deaths of nearly 1 in 10 Americans. In seniors, the single most common life-threatening disease is congestive heart failure and for these patients, abnormalities of diastolic function play a critical role in the pathophysiology of their disease. The sponsor's research has demonstrated that healthy but sedentary aging leads to atrophy and stiffening of the heart with reduced myocardial and chamber compliance. In contrast, highly competitive senior runners had cardiac compliance that was indistinguishable from healthy young individuals suggesting that lifelong exercise training prevented this stiffening. However, prolonged and intense exercise training (4-6 hrs/wk for 1 yr) failed to restore cardiac compliance in healthy seniors despite other health benefits.

Why did this year of training fail to restore cardiac compliance? New evidence suggests that the structural plasticity of myocardial cells in the elderly may be functionally constrained by the accumulation of toxic metabolites called advanced glycation end-products (AGEs). AGEs are arrays of protein which have been non-enzymatically cross-linked by sugars; these arrays increase the stiffness of arterial walls and the myocardium. Investigators have recently developed a drug capable of cleaving AGE cross-links. Termed ALT-711, this drug has been shown to be safe in human studies with varying degrees of efficacy on endpoints such as blood pressure and non-invasive indices of diastolic function. Based on animal studies, we hypothesize that AGE cross-links must be broken before a meaningful improvement in cardiac compliance can occur with exercise training in sedentary seniors.

Hypothesis: We hypothesize that AGE cross-links must be broken before a meaningful improvement in cardiac compliance can occur with exercise training in previously sedentary seniors; the combination of the AGE cross-link breaker, ALT-711, with exercise training will be superior to either intervention alone in improving cardiac compliance in these subjects.

Specific Aim: To test this hypothesis, we will study four groups of previously sedentary senior subjects for one year with the following interventions: A) sedentary controls taking placebo; B) sedentary subjects taking ALT-711; C) subjects undergoing moderate intensity exercise training while taking placebo and D) subjects undergoing moderate intensity exercise training while taking ALT-711.

A comprehensive set of "Baseline Testing" (prior to the one year intervention) and "Follow-up Testing" (after the one year intervention) will take place to assess the effects of the intervention. This testing will include submaximal and maximal exercise testing as well as comprehensive invasive (right heart catheterization) and non-invasive (ultrasound, MRI) measures of cardiac mechanics, relaxation and morphology. From these data, the following indices of diastolic and systolic function will be generated: Starling and pressure/volume curves; calculations of LV wall stress and strain; and measurements of flow propagation velocity, ejection fraction and relaxation velocity.

In assessing the risk benefit ratio for our study, the major benefits include: 1) obtaining meaningful information for society regarding the effects of ALT-711 and moderate intensity exercise training on the compliance of the left ventricular chamber; 2) obtaining important information for the subject regarding ambulatory blood pressure, exercise performance, cardiac morphology and cardiac function; and 3) providing the subject one year of supervised moderate intensity exercise training or yoga training, each with associated health benefits. The risks of the study are primarily imposed by the dosing of our investigational drug, which has a favorable side effect profile, and the placement of a peripherally inserted right heart catheter, which carries minimal risk when placed by an experienced cardiovascular specialist in a catheterization lab. Hence, in the final analysis, we feel the benefits to both the enrolled individual and to society far outweigh the risks of participation.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
62

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Dallas, Texas, United States, 75231
        • The Institute for Exercise and Environmental Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

65 years to 80 years (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Healthy senior status (age > 64)
  • Body mass index < 30
  • Sedentary status (not exercising > 2/wk)

Exclusion Criteria:

  • Hypertension
  • Diabetes
  • Heart Failure
  • Asthma
  • Chronic obstructive pulmonary disease
  • Coronary artery disease (as evidenced by angina or prior myocardial infarction)
  • Cerebrovascular disease (as evidenced by prior transient ischemic attack or stroke)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Aerobic Exercise Training + Placebo
Behavioral: Aerobic Exercise Training
Aerobic exercise training consisting of exercise of choice (walking, eliptical machine, stairstepper, stationary bike, etc.) 4 times per week for 40 minutes at a base pace, and two higher intensity steady state sessions per month.
Experimental: Tai Chi and/or Yoga Training + Placebo
Behavioral: Tai Chi and/or Yoga Training
Tai Chi or Yoga training includes a series of exercises that improve flexibility, balance and coordination. Training will be supervised by trained instructors. This training will occur 3 times per week.
Experimental: Aerobic Exercise Training + Alagebrium
Behavioral: Aerobic Exercise Training
Aerobic exercise training consisting of exercise of choice (walking, eliptical machine, stairstepper, stationary bike, etc.) 4 times per week for 40 minutes at a base pace, and two higher intensity steady state sessions per month.
Drug: Alagebrium (generic: ALT-711)
The dosage of our drug, ALT-711, will be one 100 mg caplet by mouth twice per day for 12 months. Total dose per day 200 mg.
Experimental: Tai Chi and/or Yoga Training + Alagebrium
Behavioral: Tai Chi and/or Yoga Training
Tai Chi or Yoga training includes a series of exercises that improve flexibility, balance and coordination. Training will be supervised by trained instructors. This training will occur 3 times per week.
Drug: Alagebrium (generic: ALT-711)
The dosage of our drug, ALT-711, will be one 100 mg caplet by mouth twice per day for 12 months. Total dose per day 200 mg.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Left ventricular compliance and distensibility.
Time Frame: One year after enrollment in the study.
One year after enrollment in the study.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Texas Southwestern Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute on Aging (NIA)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Benjamin D Levine, M.D., University of Texas Southwestern Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2008

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 13, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 16, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 17, 2009

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 7, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 4, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2020

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • STU 122010-189
  • R01AG017479 (NIH)
  • IRB#032008-012
  • IND72,382

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Ventricular Function

Clinical Trials on Aerobic Exercise Training

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings