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Cardiovascular Mechanisms of Exercise Intolerance in Diabetes and the Role of Sex

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ClinicalTrials.gov Identifier: NCT03419195
Recruitment Status : Recruiting
First Posted : February 1, 2018
Last Update Posted : February 12, 2018
Sponsor:
Collaborator:
VA Eastern Colorado Health Care System
Information provided by (Responsible Party):
University of Colorado, Denver

Brief Summary:

This study will define the relationship of cardiac, vascular function and skeletal muscle blood flow (individually and together) to cardiovascular exercise capacity in in men and women with and without type 2 diabetes (T2DM). Identification of differences in the effects of exercise training on the integrated cardiovascular system and metabolism in men and women with and without T2DM will reveal specific adaptive responses to exercise.This study will evaluate & compare exercise function in a total of 60 subjects from the Denver area (30 people with T2DM and 30 overweight control subjects).

Specific Aim 1: To test the hypothesis that the integration of cardiac function, macrovascular function, and microvascular function is impaired in T2D and correlates with cardiovascular exercise capacity (CVEC) impairment.

Specific Aim 2: To test the hypothesis that exercise training will elicit adaptive responses in cardiac and vascular function, muscle perfusion and metabolism with differences by T2D status.

Differences between the exercise responses in people with T2DM and healthy people will help further identify the disease process of T2DM and direct future research of treatments and interventions.


Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Healthy Overweight Cardiovascular Risk Factor Other: Cardiovascular exercise training Not Applicable

Detailed Description:

It is well established that functional exercise capacity and peak oxygen uptake (VO2) are reduced in patients with type 2 diabetes mellitus (T2DM) compared with healthy counterparts. The mechanisms underlying the exercise deficit in T2DM remain largely unknown, but previous work has suggested that reduced exercise blood flow and impaired submaximal VO2 may be contributing factors. Both of these findings are consistent with a peripheral impairment of skeletal muscle oxygen delivery, oxygen utilization, or both. Indeed, dysfunction of skeletal muscle metabolism plays a key role in the pathophysiology of T2DM, and considerable work has described abnormalities of oxidative function in the skeletal muscle of people with T2DM. Given this, it is likely that the causes of exercise intolerance in T2DM may relate to specific defects at the level of the skeletal muscle, particularly given that skeletal muscle blood flow and oxidative capacity are impaired in diabetes. However, to the knowledge of the investigators, no one has related these peripheral muscle abnormalities to the diminished exercise function in this patient group.

The overarching hypothesis for the proposed research is that impaired CVEC in T2DM is the result of preclinical cardiac, vascular dysfunction and skeletal muscle perfusion abnormalities. Exercise training will improve CVEC and will reveal specific reversible therapeutic aspects of this pathology. The investigators will first determine the impairments and then evaluate responses to an established cardiac rehabilitation exercise training program, established to improve fitness in people with and without diabetes. Given the greater CVEC abnormalities observed in women, sex differences will be evaluated for each aim.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Cardiovascular Mechanisms of Exercise Intolerance in Diabetes and the Role of Sex
Actual Study Start Date : February 7, 2018
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cardiovascular Exercise
Cardiovascular exercise training is conducted 3 times a week for 3 months under the supervision of experienced exercise specialists. Each session will last a total of one hour - a 5 minute warm up, 50 minutes of cardiovascular exercise using a treadmill, stationary bike, elliptical, rowing machine, or a combination of machines, and a 5 minute cool-down. Exercise intensity will be based on heart rate. There will also be a 3 week ramp-up period to get accustomed to exercising. This is in addition to the 3 month intervention.
Other: Cardiovascular exercise training
Following the completion of baseline testing, both subject groups will undergo supervised cardiovascular exercise training 3 times per week for 3 months (plus a 3 week ramp-up). Exercise training will take place on a treadmill, stationary bicycle, elliptical, rowing machine, or combination of machines. Each session will last 1 hour, which includes a 5 minute warm-up, 50 minutes of exercise, and a 5 minute cool down.
Other Name: Exercise Training




Primary Outcome Measures :
  1. Change in peak oxygen consumption (VO2peak) [ Time Frame: Through study completion, approximately 4 months ]
    Subjects' peak oxygen consumption will be tested on a stationary bike before and after 3 months of exercise

  2. Change in insulin sensitivity [ Time Frame: Through study completion, approximately 4 months ]
    The investigators will evaluate the changes in insulin sensitivity utilizing a euglycemic insulin clamp

  3. Change in muscular mitochondrial function [ Time Frame: Through study completion, approximately 4 months ]
    The investigators will examine mitochondrial function using magnetic resistance (MR) spectroscopy during single leg calf exercise

  4. Change in cardiovascular function [ Time Frame: Through study completion, approximately 4 months ]
    The investigators will examine the change in cardiovascular function using novel cardiac MRI techniques

  5. Change in muscular respiration, function, and vascularization [ Time Frame: Through study completion, approximately 4 months ]
    The investigators will examine various changes in the vastus lateralis assessed by muscle biopsy


Secondary Outcome Measures :
  1. Changes from baseline in echocardiographic measures [ Time Frame: Through study completion, approximately 4 months ]
    Potential change in cardiac function will be assessed by echocardiography before and after 3 months of exercise

  2. Change from baseline in peak dilation of femoral artery diameter [ Time Frame: Through study completion, approximately 4 months ]
    Change in the response of the femoral artery to hyperemia will be assessed before and after 3 months of exercise

  3. Change in (non-invasively measured) deoxygenated hemoglobin concentration in the gastrocnemius during exercise [ Time Frame: Through study completion, approximately 4 months ]
    Deoxygenated hemoglobin concentration will be measured using near-infrared spectroscopy during sub-maximal exercise before and after 3 months of exercise



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Ages Eligible for Study:   30 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Men and women with and without type 2 diabetes
  • BMI 25-40
  • Sedentary subjects not participating in a regular exercise program (<one bout of exercise/week)

Exclusion Criteria:

  • Documented cardiovascular disease
  • Uncontrolled hypertension: disease systolic blood pressure (SBP) > 150, diastolic blood pressure (DBP)> 110
  • Obstructive pulmonary disease or asthma
  • Peripheral neuropathy
  • Physical impairment that would limit exercise ability
  • Subjects taking beta blockers, calcium channel blockers, insulin, or Thiazolidinediones (TZD)
  • Current or past smoking within the last 2 years
  • Anemia
  • Control HbA1c > 5.7, T2DM HbA1c > 10
  • Pregnant, nursing or hormonal therapy (other than contraceptives)
  • Peri or post-menopausal women
  • Type 1 diabetes
  • Hepatic or renal disease.
  • Peptic ulcer disease.

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): NCT03419195


Contacts
Contact: Deirdre Rafferty, MS 720-848-6688 deirdre.rafferty@ucdenver.edu
Contact: Judy Regensteiner, PhD 303-724-2247 judy.regensteiner@ucdenver.edu

Locations
United States, Colorado
University of Colorado, Anschutz Medical Campus Recruiting
Aurora, Colorado, United States, 80045
Contact: Deirdre Rafferty, MS    720-848-6688    deirdre.rafferty@ucdenver.edu   
Contact: Ian Leavitt, MS    720-848-7103    ian.leavitt@ucdenver.edu   
Principal Investigator: Judy Regensteiner, PhD         
Principal Investigator: Jane Reusch, MD         
Sponsors and Collaborators
University of Colorado, Denver
VA Eastern Colorado Health Care System
Investigators
Principal Investigator: Judy Regensteiner, PhD University of Colorado, Denver

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT03419195     History of Changes
Other Study ID Numbers: 17-0356
First Posted: February 1, 2018    Key Record Dates
Last Update Posted: February 12, 2018
Last Verified: February 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Colorado, Denver:
Type 2 Diabetes
Overweight
Exercise Training
Exercise Impairment
Healthy Control
Veteran
Blood Flow

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Overweight
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Body Weight
Signs and Symptoms