Muscle Insulin Resistance In Aging (MIRAGE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2013 by University of Pittsburgh
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Bret Goodpaster, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01808924
First received: January 13, 2012
Last updated: March 8, 2013
Last verified: March 2013
  Purpose

The overall objective of this project is to thoroughly investigate the effects of diet-induced weight loss in the absence of or in combination with exercise on skeletal muscle IR, energy metabolism and function. These studies will significantly improve our understanding of the fundamental biochemical and molecular factors linking intervention-induced changes in mitochondria, oxidative stress, lipotoxicity, IR, and loss of muscle function in aging humans.


Condition Intervention
Aging
Other: Exercise training protocol
Other: Dietary
Other: Educational control.

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Health Services Research
Official Title: Muscle Insulin Resistance In Aging

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • muscle biopsy [ Time Frame: pre/post intervention ] [ Designated as safety issue: No ]
    A muscle biopsy will be performed before the start of each clamp and also right before the end of each clamp to determine changes in the primary outcome (independent) variables intramyocellular lipid (IMCL) content and oxidative enzyme capacity.


Estimated Enrollment: 120
Study Start Date: December 2011
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Energy Restriction-Induced Weight Loss. (DIWL)
The goal of the weight loss intervention will be to produce a weight loss of 10% body weight. A reduction of 500-1000 kcal/day - based on baseline weight -and low fat (<30% of calories from fat) diet will be used as part of the weight loss intervention. Particular efforts will be made to maintain the recommended daily protein, vitamin and mineral intake. The weight loss program will be administered individually to subjects so that the registered dietician will meet with each subject weekly to provide dietary prescription and record body weight. In order to eliminate the confounding effects of acute caloric restriction on insulin sensitivity, the dietician will keep subjects weight stable during the last two weeks.
Other: Dietary
The goal of the weight loss intervention will be to produce a weight loss of 10% body weight. A reduction of 500-1000 kcal/day - based on baseline weight -and low fat (<30% of calories from fat) diet will be used as part of the weight loss intervention. Particular efforts will be made to maintain the recommended daily protein, vitamin and mineral intake. The weight loss program will be administered individually to subjects so that the registered dietician will meet with each subject weekly to provide dietary prescription and record body weight. In order to eliminate the confounding effects of acute caloric restriction on insulin sensitivity, the dietician will keep subjects weight stable during the last two weeks.
Other Names:
  • diet
  • nutrition
Exercise training protocol. (WLEX)

Participants will complete a progressive 6-month exercise-training program, 4-5 days per week, 45 min per session (180 min per week), consisting mostly of walking (both outside and on an indoor treadmill) but with the option to include both stationary cycling and rowing, similar to what we have utilized previously to elicit significant improvements in insulin sensitivity in both middle-age and older adults (52-55).

Beginning at week 8, these subjects will also perform 2 non-consecutive resistance exercise sessions per week, 30 min per session, focused on major muscle groups using Keiser pneumatic-powered machines (total days of exercise will still be 4 to 5).

Other: Exercise training protocol

Participants will complete a progressive 6-month exercise-training program, 4-5 days per week, 45 min per session (180 min per week), consisting mostly of walking (both outside and on an indoor treadmill) but with the option to include both stationary cycling and rowing, similar to what we have utilized previously to elicit significant improvements in insulin sensitivity in both middle-age and older adults (52-55).

Beginning at week 8, these subjects will also perform 2 non-consecutive resistance exercise sessions per week, 30 min per session, focused on major muscle groups using Keiser pneumatic-powered machines (total days of exercise will still be 4 to 5)

Other Names:
  • cardio
  • resistance training
Educational control.

Educational control. Subjects in the control arm will require special attention for compliance.

This will involve frequent (biweekly) educational sessions, including topics such as medications. We will in part model this program on what we have developed and implemented for the LIFE study, a large, multi-center randomized controlled exercise trial in older adults (57; 58). The primary purpose to ensure compliance is not to equate their contact time or exposure time to the exercise group, but rather to increase the chance to detect differences in the outcomes between the control group and treatment groups. At the end of the 6 months these participants will be offered a structured weight loss and exercise program, which should greatly aid in recruitment and adherence.

Other: Educational control.
Subjects in the control arm will require special attention for compliance. This will involve frequent (biweekly) educational sessions, including topics such as medications. We will in part model this program on what we have developed and implemented for the LIFE study, a large, multi-center randomized controlled exercise trial in older adults (57; 58). The primary purpose to ensure compliance is not to equate their contact time or exposure time to the exercise group, but rather to increase the chance to detect differences in the outcomes between the control group and treatment groups. At the end of the 6 months these participants will be offered a structured weight loss and exercise program, which should greatly aid in recruitment and adherence.
Other Names:
  • education
  • behavioral

Detailed Description:

Aging is associated with alterations in skeletal muscle energy metabolism, insulin resistance and a higher prevalence of type 2 diabetes mellitus (T2DM). Aging is also associated with a progressive loss of muscle mass and increased adiposity, known as sarcopenic obesity, which leads to mobility limitations and disability. However, the causes of insulin resistance and sarcopenia in humans are not known. This project will provide novel information regarding potential factors underlying both metabolic dysfunction and sarcopenia in aging muscle - namely, mitochondria and the accumulation of intramyocellular lipids. Within this conceptual framework we will help elucidate the biological underpinnings of these two significant health problems related to aging. In addition, we will provide intervention-based evidence to better understand these complex age-related disorders and whether mitochondria or intramyocellular lipids are modifiable targets for improved prevention or treatment strategies for metabolic and muscle dysfunction. Therefore, our overall objectives are to employ highly innovative methods in muscle biopsy specimens in order to determine the functional and clinically relevant consequences of these interventions as well as alterations in several novel biochemical and molecular factors potentially underlying these intervention effects on human skeletal muscle. Our primary approach to address all aims of the proposed studies is to conduct a 6-month randomized controlled trial in obese (BMI ≥ 30 kg/m2) sedentary older men and women 65-80 years of age.

  1. Control (health education) group (CON): Subjects will not receive specific exercise or dietary education or prescription, but will be asked to participate in biweekly health education sessions.
  2. Diet-induced weight loss (DIWL): The goal will be to achieve a goal of 10% weight loss.
  3. Weight Loss + Exercise (WLEX): This group will receive exactly the same dietary intervention as the respective DIWL group. In addition, subjects will be complete a progressive, moderate intensity supervised This is a single-site randomized controlled trial. The analysis of each of the aims will involve multiple steps and draw on statistical methods ranging from simple descriptive statistics to the modeling of repeated measures outcome data accounting for potential missing observations.

The major outcomes of the study, the muscle biopsy parameters, insulin sensitivity, muscle mass, strength, power and quality, will be measured at entry into the study and at the end of the study.

  Eligibility

Ages Eligible for Study:   65 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 65-80 years of age
  • Stable weight (No Gain/Loss of > 10 lbs in 6 months)
  • Sedentary (≤ 1 continuous exercise/week)
  • Non-smoker
  • BMI ≥ 30 kg/m2
  • Resting Blood Pressure ≤ 150mmHg systolic and ≤ 95 mmHg diastolic
  • Note from PCP/Cardiologist for exercise clearance if positive stress test
  • Symptoms were observed from exercise test
  • Independent in self blood glucose monitoring (those with diabetes only)

Exclusion Criteria:

  • Clinically significant CVD including h/o MI
  • Peripheral Vascular Disease
  • Section: Section 3 - Human Subjects
  • Hepatic, renal, muscular/neuromuscular, or active hematologic/oncologic disease
  • Clinically diminished pulse
  • Presence of bruits in lower extremities
  • Previous history of pulmonary emboli
  • Peripheral Neuropathy
  • Anemia (Hematocrit <34%)
  • Any contraindications to moderate exercise (Please specify)
  • Inability and/ or willingness to comply with the protocol as written
  • Active alcohol or substance abuse (Past 5 Years)
  • Total cholesterol >300 mg/dL
  • Triglycerides >350 mg/dL
  • ALT >80, AST>80, Alk Phos >240
  • Proteinuria (defined as > 1+)
  • Hypothyroidism (sTSH>8)
  • Fasting Glucose > 250 mg/dl
  • Hemoglobin A1c > 8.5%
  • Currently taking blood thinners such as Coumadin, Lovenox etc
  • Currently taking any medications that can alter glucose homeostasis (steroids, glucocorticoids,nicotinic acid)
  • Currently taking thiazolidinediones or insulin
  • Females currently on hormone replacement therapy (HRT) less than 6 months
  • Claustrophobia
  • Previous difficulty with lidocaine or other local anesthetic
  • Stress test symptoms:

    • Positive ECG (> 2mm ST segment depression) without PCP cardiologist permission to participate
    • Signs or symptoms of cardiovascular decomposition (hypotensive response to exercise)
    • Onset of angina or angina like symptoms, shortness of breath, change in heart rhythm, signs of poor perfusion (light-headedness), tightness,
    • Hypotension
  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: NCT01808924

Contacts
Contact: Nicole L Helbling, MS, RN 412-692-2285 nlr8@pitt.edu
Contact: Heidi L Yarnal, BS 412-692-2848 hee4@pitt.edu

Locations
United States, Pennsylvania
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Nicole L Helbling, MS, RN    412-692-2285    nlr8@pitt.edu   
Contact: Heidi L Yarnal, BS    412-692-2848    hee4@pitt.edu   
Sub-Investigator: Frederico Toledo, MD         
Sub-Investigator: Nicole L Helbling, MS, RN         
Sub-Investigator: Maja Stefanovic-Racic, MD         
Sub-Investigator: John Dube, PhD         
Sub-Investigator: Stuart Seigel, MD         
Sub-Investigator: Jason Ng, MD         
Sub-Investigator: Paul Coen, PhD         
Sub-Investigator: Steve Anthony, MS         
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Bret Goodpaster, PhD University of Pittsburgh
  More Information

No publications provided

Responsible Party: Bret Goodpaster, Professor, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01808924     History of Changes
Other Study ID Numbers: PRO11080592, 2R01AG021961-05
Study First Received: January 13, 2012
Last Updated: March 8, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Pittsburgh:
aging
insulin resistance
diabetes
sarcopenia in aging
muscle mitochondria
intramyocellular lipids

Additional relevant MeSH terms:
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Insulin, Globin Zinc
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 21, 2014