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Identification of Novel Skeletal Muscle-derived Factors That Promote Lipid Oxidation (Columbus)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Sanford-Burnham Medical Research Institute
Takeda
Information provided by (Responsible Party):
Translational Research Institute for Metabolism and Diabetes, Florida
ClinicalTrials.gov Identifier:
NCT01911091
First received: July 24, 2013
Last updated: November 18, 2014
Last verified: November 2014
  Purpose

The purpose of this study is to collect data to help researchers identify factors, such as certain proteins or genetic codes, that are secreted from muscle that are associated with the beneficial effects of exercise.


Condition Intervention
Obesity
Disorder of Lipid Storage and Metabolism
Lipid Metabolism Disorders
Metabolic Disorder
Behavioral: Exercise

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Identification of Novel Skeletal Muscle-derived Factors That Promote Lipid Oxidation in Both Skeletal Muscle and Adipose Tissue

Resource links provided by NLM:


Further study details as provided by Translational Research Institute for Metabolism and Diabetes, Florida:

Primary Outcome Measures:
  • Measure change in mitochondrial capacity [ Time Frame: Baseline (Day -6), Day 18 ] [ Designated as safety issue: No ]

    The difference will be measured in obese, lean and athletic participants.

    The Phosphocreatine (PCr) recovery time constant and the PCr level in oxygenated muscle at rest will be used to calculate maximum mitochondrial capacity.



Secondary Outcome Measures:
  • Measure change of expression of proteins [ Time Frame: Baseline (Day -6), Day 0, Day 5, Day 12, Day 18 ] [ Designated as safety issue: No ]

    The difference will be measured in obese, lean and athletic participants.

    This will be taken from muscle biopsy and/or blood plasma samples obtained at baseline, before and after exercise.


  • Measure change in mRNA/miRNA levels [ Time Frame: Baseline (Day -6), Day 0, Day 5, Day 12, Day 18 ] [ Designated as safety issue: No ]

    The difference will be measured in obese, lean and athletic participants.

    This will be taken from muscle biopsy and/or blood plasma samples obtained at baseline, before and after exercise.



Estimated Enrollment: 56
Study Start Date: July 2013
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1 - Regular exercise
Alternate interval training and aerobic training and exercise
Behavioral: Exercise
A 5-minute warm-up and a 5-minute cool-down prior to and following each exercise session, respectively. There will be alternating days of interval training and aerobic training. The interval training will be performed on an upright stationary bike, while the aerobic training will be performed on a treadmill. The interval training will consist of five-minute bouts of higher intensity alternated with 4 minutes of lower intensity for a total duration of 45 minutes. Intensity will increase each week. The aerobic training component will be fixed at a moderate intensity, but will increase in duration each week from 45 minutes to 75 minutes to 90 minutes during the third and final week.
No Intervention: Group 2 - Athlete exercise
Athletes are not given any intervention
No Intervention: Group 3 - Obese No Exercise
The Obese group will not receive intervention

Detailed Description:

Study Objectives:

  1. To identify specific changes in messenger ribonucleic acid (mRNA)/micro ribonucleic acid (miRNA) expression in muscle associated with higher or lower relative measures of mitochondrial capacity and fat oxidation.
  2. To identify secreted factors/miRNAs that specifically relate to the metabolic response of muscle and that are present after a single initial bout of exercise.
  3. To collect the appropriate clinical samples (muscle and adipose tissue, plasma/serum) to enable validation of myokines associated with changes in oxygen consumption/mitochondrial content via in vivo and in vitro discovery efforts.
  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Applicable to all Groups

  • Healthy men and women, aged 18 - 40, inclusive.
  • Willing to stop alcohol and caffeine consumption for 48 hours preceding each blood draw

Applicable to Group 1

  • BMI between 22 and 29.9 kg/m2
  • Not involved in regular exercise program
  • Willing to exercise every day for the study period

Applicable to Group 2

  • BMI between 22 and 29.9 kg/m2
  • Maximal oxygen uptake (VO2max) ≥ 45 ml/kg fat-free mass

    /min

  • Engaged in a minimum of 1.5 h of moderate to vigorous intensity aerobic exercise 3 times/ week

Applicable to Group 3

  • BMI ≥ 30 kg/m2 and weight ≤ 350 lbs
  • Not involved in a regular exercise program

Exclusion Criteria:

Applicable to All Groups

  • History of Type 2 Diabetes
  • "Unfavorable anatomy" for continuous venous blood sample collection
  • Abnormal resting ECG
  • Significant renal, cardiac, liver, lung, or neurological disease (controlled hypertension is acceptable if baseline bp < 140/90 on medications)
  • Use of drugs known to affect energy metabolism or body weight: including, but not limited to: orlistat, sibutramine, ephedrine, phenylpropanolamine, corticosterone, etc
  • Current treatment with blood thinners or anti-platelet medications that cannot be safely stopped for testing procedures
  • New onset (<3 months on a stable regime) use of oral contraceptives or hormone replacement therapy
  • Alcohol or other drug abuse
  • Smoking within the past 3 months
  • Females that are currently or have been pregnant or are currently or have nursed a child within the last 12 months (minimum).
  • Parental enrollment into the study that compromises the well being of the child [no partner or connected caregiver]
  • Unwilling or unable to abstain from caffeine or alcohol 48 hours prior to metabolic rate measurements
  • Increased liver function tests
  • Metal objects that would interfere with the measurement of body composition /magnetic resonance spectroscopy such as implanted rods, surgical clips, etc
  • Any New York Heart Association class of congestive heart failure
  • History of deep vein thrombosis or pulmonary embolism
  • Significant varicose veins
  • Abnormal blood count/Anemia, or blood donation within the last 2 months
  • Major surgery on the abdomen, pelvis, or lower extremities within previous 3 months
  • Bariatric surgery or liposuction within the previous 3 years
  • Cancer (active malignancy with or without concurrent chemotherapy)
  • Rheumatoid disease
  • Bypass graft in limb
  • Known genetic factor (Factor V Leiden, etc) or hypercoagulable state
  • Diagnosed peripheral arterial or vascular disease, or intermittent claudication
  • Family history of primary deep vein thrombosis or pulmonary embolism
  • Peripheral neuropathy
  • Claustrophobia
  • Frequent nocturnal urination and/or sleep apnea
  • Presence of any condition that, in the opinion of the investigator, compromises participant safety or data integrity or the participants' ability to complete the training protocol

Applicable to Group 2

  • Gait problems
  • Major Depression
  • Presence of an eating disorder or eating attitudes/behaviors that could interfere with the study completion
  • Unwilling or unable to complete the protocol

Applicable to Group 3

  • HbA1c ≥ 6.5% (O)
  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: NCT01911091

Locations
United States, Florida
Translational Research Institute for Metabolism and Diabetes
Orlando, Florida, United States, 32804
Sponsors and Collaborators
Translational Research Institute for Metabolism and Diabetes, Florida
Sanford-Burnham Medical Research Institute
Takeda
Investigators
Principal Investigator: Steven R Smith, MD Translational Research Institute for Metabolism and Diabetes
  More Information

Additional Information:
Publications:

Responsible Party: Translational Research Institute for Metabolism and Diabetes, Florida
ClinicalTrials.gov Identifier: NCT01911091     History of Changes
Other Study ID Numbers: TRIMDFH 460196
Study First Received: July 24, 2013
Last Updated: November 18, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Translational Research Institute for Metabolism and Diabetes, Florida:
skeletal muscle
adipose tissue
metabolism
oxidation
mitochondrial capacity

Additional relevant MeSH terms:
Disease
Lipid Metabolism Disorders
Metabolic Diseases
Sphingolipidoses
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Genetic Diseases, Inborn
Lipid Metabolism, Inborn Errors
Lipidoses
Lysosomal Storage Diseases
Lysosomal Storage Diseases, Nervous System
Nervous System Diseases
Metabolism, Inborn Errors
Pathologic Processes

ClinicalTrials.gov processed this record on November 25, 2014