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

Primary Purpose

Obesity, Disorder of Lipid Storage and Metabolism, Lipid Metabolism Disorders

Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Exercise
Sponsored by
AdventHealth Translational Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Obesity focused on measuring skeletal muscle, adipose tissue, metabolism, oxidation, mitochondrial capacity

Eligibility Criteria

18 Years - 40 Years (Adult)All SexesAccepts Healthy Volunteers

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)

Sites / Locations

  • Translational Research Institute for Metabolism and Diabetes

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

No Intervention

No Intervention

Arm Label

Group 1 - Regular exercise

Group 2 - Athlete exercise

Group 3 - Obese No Exercise

Arm Description

Alternate interval training and aerobic training and exercise

Athletes are not given any intervention

The Obese group will not receive intervention

Outcomes

Primary Outcome Measures

Measure change in mitochondrial capacity
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
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
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.

Full Information

First Posted
July 24, 2013
Last Updated
June 6, 2023
Sponsor
AdventHealth Translational Research Institute
Collaborators
Sanford-Burnham Medical Research Institute, Takeda
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1. Study Identification

Unique Protocol Identification Number
NCT01911091
Brief Title
Identification of Novel Skeletal Muscle-derived Factors That Promote Lipid Oxidation (Columbus)
Acronym
Columbus
Official Title
Identification of Novel Skeletal Muscle-derived Factors That Promote Lipid Oxidation in Both Skeletal Muscle and Adipose Tissue
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 2013 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AdventHealth Translational Research Institute
Collaborators
Sanford-Burnham Medical Research Institute, Takeda

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
Study Objectives: 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. 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Disorder of Lipid Storage and Metabolism, Lipid Metabolism Disorders, Metabolic Disorder
Keywords
skeletal muscle, adipose tissue, metabolism, oxidation, mitochondrial capacity

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
56 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group 1 - Regular exercise
Arm Type
Experimental
Arm Description
Alternate interval training and aerobic training and exercise
Arm Title
Group 2 - Athlete exercise
Arm Type
No Intervention
Arm Description
Athletes are not given any intervention
Arm Title
Group 3 - Obese No Exercise
Arm Type
No Intervention
Arm Description
The Obese group will not receive intervention
Intervention Type
Behavioral
Intervention Name(s)
Exercise
Intervention Description
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.
Primary Outcome Measure Information:
Title
Measure change in mitochondrial capacity
Description
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.
Time Frame
Baseline (Day -6), Day 18
Secondary Outcome Measure Information:
Title
Measure change of expression of proteins
Description
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.
Time Frame
Baseline (Day -6), Day 0, Day 5, Day 12, Day 18
Title
Measure change in mRNA/miRNA levels
Description
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.
Time Frame
Baseline (Day -6), Day 0, Day 5, Day 12, Day 18

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven R Smith, MD
Organizational Affiliation
Translational Research Institute for Metabolism and Diabetes
Official's Role
Principal Investigator
Facility Information:
Facility Name
Translational Research Institute for Metabolism and Diabetes
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States

12. IPD Sharing Statement

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

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