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

Type 2 Diabetes Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04754581
• Other study ID #: 1581803
• Status: Recruiting
• Phase: N/A
• Start date: March 30, 2021
• Est. completion date: August 2024

Study information

• Verified date: January 2024
• Source: AdventHealth Translational Research Institute
• Contact: Recruitment Department
• Phone: 407-303-7100
• Email: Fh.tri.recruitment[@]adventhealth.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: August 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Insulin Resistance
• Type 2 Diabetes

Intervention

Other:
• Maximal ATP Production (ATPmax)
ATPmax will be measured in order to determine in vivo mitochondrial capacity. The magnetic resonance scans to measure mitochondrial energetics will also be performed.
• Exercise Testing (VO2max)
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.

Procedure:
• Muscle Biopsy
Sample muscle cells from the left leg Vastus Lateralis (thigh) muscle.
• Adipose Tissue Biopsy
Sample fat tissue from the abdomen.

Other:
• Hyperinsulinemic euglycemic clamp
Measurement of insulin sensitivity.
• PET imaging
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.

Locations

Country	Name	City	State
United States	AdventHealth Translational Research Institute	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AdventHealth Translational Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	24 hours
Primary	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.	24 hours

External Links

•   Website for AdventHealth Translational Research Institute