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Dynamic in Vivo PET Imaging and ex Vivo Biopsies From Skeletal Muscle and Adipose Tissue to Investigate the Effects of Exercise on Insulin Resistance and Mitochondrial Energetics in Type 2 Diabetes (EXPET)

Primary Purpose

Type 2 Diabetes

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Maximal ATP Production (ATPmax)
Exercise Testing (VO2max)
Muscle Biopsy
Adipose Tissue Biopsy
Hyperinsulinemic euglycemic clamp
PET imaging
Sponsored by
AdventHealth Translational Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Type 2 Diabetes

Eligibility Criteria

30 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. Age 30-65 years
  2. Men and women
  3. Body mass index (BMI) between 25 and 45 kg/m2
  4. Sedentary (1 day or less per week of structured exercise)
  5. Type 2 diabetes mellitus determined by self-report or by a fasting glucose >126mg/dl
  6. Weight stable (± 2 kg) for prior 3 months
  7. Willing to commit to the schedule of assessment visits, including the exercise intervention

Exclusion Criteria:

  1. Currently taking insulin, injectable incretin mimetics and thiazolidinediones
  2. Taking more than two glucose-lowering medications
  3. Resting blood pressure ≥ 160/100 mm Hg
  4. Triglycerides ≥ 500 mg/dL
  5. Any renal, cardiac, liver, lung, or neurological disease that in the opinion of the principal investigator would compromise participant safety or the participants' ability to complete the exercise training protocol
  6. Any significant disease or unstable medical condition (i.e., coronary heart disease, chronic renal failure, chronic hepatic disease, severe pulmonary disease)
  7. Presence of clinically significant abnormalities on electrocardiogram (ECG) that is a contra-indication to exercise training
  8. Pulse check ("Allen test") indicates participant has poor blood flow in the hands
  9. Cancer (active malignancy with or without concurrent chemotherapy; except for basal cell carcinoma)
  10. Pregnancy during the previous 6 months, lactating, or planned pregnancy in the next year
  11. Use of drugs known to affect energy metabolism or body weight: including, but not limited to orlistat, sibutramine, ephedrine, phenylpropanolamine, corticosterone, etc
  12. Current treatment with blood thinners or anti-platelet medications that cannot be safely stopped for testing procedures
  13. Participant is currently taking anti-inflammatory medication or has had inflammatory medication within 1 week prior to screening (including over the counter formulations: e.g. Aleve, Motrin, Ibuprofen, Naproxen, low dose ASA.
  14. New onset (<3 months on a stable regime) hormone replacement therapy
  15. Current use of beta-adrenergic blocking agents
  16. Major surgery on the abdomen, pelvis, or lower extremities within previous 3 months
  17. Increased liver function tests (AST/ALT/GGT/or alkaline phosphatase greater than 2.5 times the upper limit of normal)
  18. Abnormal blood count/anemia, blood transfusion or blood donation within the last 2 months
  19. Current smokers (smoking within the past 3 months prior to screening visit, including any/all tobacco products)
  20. Current drug or alcohol abuse/dependence
  21. Metal implants (pace-maker, aneurysm clips) based on investigator's judgment at screening
  22. Not physically capable of performing the exercise required of the study protocols
  23. Plans to be away >2 weeks in the next 3 months
  24. Unable to participate in Magnetic Resonance Imaging (MRI) assessments due to physical limitations of equipment tolerances (e.g. MRI bore size) based on investigator's judgment at screening.
  25. Unable to tolerate MRI or claustrophobia.
  26. Nickel allergy
  27. Lidocaine allergy
  28. Unable or unwilling to communicate with staff or to provide written informed consent

Sites / Locations

  • AdventHealth Translational Research InstituteRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

All Participants

Arm Description

Outcomes

Primary Outcome Measures

Individual steps of muscle glucose uptake (pre-exercise)
Muscle glucose uptake will be assessed two times (pre and post exercise intervention) on the biceps femoris and vastus lateralis through PET imaging and hyperinsulinemic euglycemic clamp.
Individual steps of muscle glucose uptake (post-exercise)
Muscle glucose uptake will be assessed two times (pre and post exercise intervention) on the biceps femoris and vastus lateralis through PET imaging and hyperinsulinemic euglycemic clamp.

Secondary Outcome Measures

Full Information

First Posted
February 5, 2021
Last Updated
August 2, 2023
Sponsor
AdventHealth Translational Research Institute
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1. Study Identification

Unique Protocol Identification Number
NCT04754581
Brief Title
Dynamic in Vivo PET Imaging and ex Vivo Biopsies From Skeletal Muscle and Adipose Tissue to Investigate the Effects of Exercise on Insulin Resistance and Mitochondrial Energetics in Type 2 Diabetes
Acronym
EXPET
Official Title
Dynamic in Vivo PET Imaging and ex Vivo Biopsies From Skeletal Muscle and Adipose Tissue to Investigate the Effects of Exercise on Insulin Resistance and Mitochondrial Energetics in Type 2 Diabetes
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 30, 2021 (Actual)
Primary Completion Date
August 2023 (Anticipated)
Study Completion Date
August 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AdventHealth Translational Research Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The overall aim of this pilot study is to investigate the effects of exercise training on skeletal muscle and adipose tissue insulin resistance in subjects with Type 2 Diabetes (T2D).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
This is a single-site, pre-post design pilot study with no control group.
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
All Participants
Arm Type
Other
Intervention Type
Other
Intervention Name(s)
Maximal ATP Production (ATPmax)
Intervention Description
ATPmax will be measured in order to determine in vivo mitochondrial capacity. The magnetic resonance scans to measure mitochondrial energetics will also be performed.
Intervention Type
Other
Intervention Name(s)
Exercise Testing (VO2max)
Intervention Description
Aerobic fitness level will be assessed while participant pedals on a stationary bicycle/walk on a treadmill. The volume of oxygen intake and carbon dioxide (CO2) production will be measured.
Intervention Type
Procedure
Intervention Name(s)
Muscle Biopsy
Intervention Description
Sample muscle cells from the left leg Vastus Lateralis (thigh) muscle.
Intervention Type
Procedure
Intervention Name(s)
Adipose Tissue Biopsy
Intervention Description
Sample fat tissue from the abdomen.
Intervention Type
Other
Intervention Name(s)
Hyperinsulinemic euglycemic clamp
Intervention Description
Measurement of insulin sensitivity.
Intervention Type
Other
Intervention Name(s)
PET imaging
Intervention Description
After an overnight fast, an intravenous catheter will be placed in each arm (one with arterial line for PET infusion, and the other for infusion of insulin, glucose, and 6,6 D2 glucose tracer. FDG-glucose will be injected followed by 90-minute PET scanning of the thigh.
Primary Outcome Measure Information:
Title
Individual steps of muscle glucose uptake (pre-exercise)
Description
Muscle glucose uptake will be assessed two times (pre and post exercise intervention) on the biceps femoris and vastus lateralis through PET imaging and hyperinsulinemic euglycemic clamp.
Time Frame
24 hours
Title
Individual steps of muscle glucose uptake (post-exercise)
Description
Muscle glucose uptake will be assessed two times (pre and post exercise intervention) on the biceps femoris and vastus lateralis through PET imaging and hyperinsulinemic euglycemic clamp.
Time Frame
24 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Age 30-65 years Men and women Body mass index (BMI) between 25 and 45 kg/m2 Sedentary (1 day or less per week of structured exercise) Type 2 diabetes mellitus determined by self-report or by a fasting glucose >126mg/dl Weight stable (± 2 kg) for prior 3 months Willing to commit to the schedule of assessment visits, including the exercise intervention Exclusion Criteria: Currently taking insulin, injectable incretin mimetics and thiazolidinediones Taking more than two glucose-lowering medications Resting blood pressure ≥ 160/100 mm Hg Triglycerides ≥ 500 mg/dL Any renal, cardiac, liver, lung, or neurological disease that in the opinion of the principal investigator would compromise participant safety or the participants' ability to complete the exercise training protocol Any significant disease or unstable medical condition (i.e., coronary heart disease, chronic renal failure, chronic hepatic disease, severe pulmonary disease) Presence of clinically significant abnormalities on electrocardiogram (ECG) that is a contra-indication to exercise training Pulse check ("Allen test") indicates participant has poor blood flow in the hands Cancer (active malignancy with or without concurrent chemotherapy; except for basal cell carcinoma) Pregnancy during the previous 6 months, lactating, or planned pregnancy in the next year 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 Participant is currently taking anti-inflammatory medication or has had inflammatory medication within 1 week prior to screening (including over the counter formulations: e.g. Aleve, Motrin, Ibuprofen, Naproxen, low dose ASA. New onset (<3 months on a stable regime) hormone replacement therapy Current use of beta-adrenergic blocking agents Major surgery on the abdomen, pelvis, or lower extremities within previous 3 months Increased liver function tests (AST/ALT/GGT/or alkaline phosphatase greater than 2.5 times the upper limit of normal) Abnormal blood count/anemia, blood transfusion or blood donation within the last 2 months Current smokers (smoking within the past 3 months prior to screening visit, including any/all tobacco products) Current drug or alcohol abuse/dependence Metal implants (pace-maker, aneurysm clips) based on investigator's judgment at screening Not physically capable of performing the exercise required of the study protocols Plans to be away >2 weeks in the next 3 months Unable to participate in Magnetic Resonance Imaging (MRI) assessments due to physical limitations of equipment tolerances (e.g. MRI bore size) based on investigator's judgment at screening. Unable to tolerate MRI or claustrophobia. Nickel allergy Lidocaine allergy Unable or unwilling to communicate with staff or to provide written informed consent
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Recruitment Department
Phone
407-303-7100
Email
Fh.tri.recruitment@adventhealth.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bret Goodpaster, PhD
Organizational Affiliation
Scientific Director | Senior Investigator
Official's Role
Principal Investigator
Facility Information:
Facility Name
AdventHealth Translational Research Institute
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Recruitment Department
Phone
407-303-7100
Email
Fh.tri.recruitment@adventhealth.com

12. IPD Sharing Statement

Links:
URL
https://www.adventhealthresearchinstitute.com/research/translational-research
Description
Website for AdventHealth Translational Research Institute

Learn more about this trial

Dynamic in Vivo PET Imaging and ex Vivo Biopsies From Skeletal Muscle and Adipose Tissue to Investigate the Effects of Exercise on Insulin Resistance and Mitochondrial Energetics in Type 2 Diabetes

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