The Effect of Oral Carnitine Supplementation on MRS-derived Mitochondrial Function

Study Overview
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Brief Summary
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This is a longitudinal study supported by Pfizer and is a collaboration between DMPI (Duke Molecular Physiology Institute) and DIAL (Duke Image Acquisition Laboratory) to measure the effects of acute exercise on carnitine and acylcarnitine levels in the muscle and on insulin sensitivity in the plasma. This pilot study seeks to explain why moderate intensity exercise provides more improvements in glucose control for pre-diabetic patients than vigorous intensity. The investigators hypothesize that moderate intensity exercise might be beneficial for elderly individuals who are overweight or obese, specifically by: 1. Reducing damaging excess protein acetylation (measured in muscle biopsy), 2. Improving the acylcarnitine/carnitine ratio (measured by MRS), 3. Improving overall mitochondrial function as reflected in reduced phosphocreatine recovery time (measured by MRS) and 4. Increasing insulin sensitivity as measured by a 4-hour oral glucose tolerance test. Investigators intend to use the results of this study to show feasibility in measuring mitochondrial function at Duke for a larger federal grant submission. Investigators hypothesize that carnitine insufficiency might contribute to mitochondrial dysfunction and obesity-related impairments in glucose tolerance and insulin action.

Official Title
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The Effect of Oral Carnitine Supplementation on MRS-derived Mitochondrial Function

Conditions
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Elderly, Pre-diabetic

Intervention / Treatment
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* Other: Acute Exercise
* Other: Acute Exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 60-80 years Moderately Overweight: BMI - 25.0 - 35.4 Sedentary - exercise ≤ 1 day/week Fasting plasma glucose: > 100 - < 126 mg/dL Readings from two separate days Exclusion Criteria: Orthopedic limitations, musculoskeletal disease and/or injury Allergic to xylocaine Inability to give blood continuously through an intravenous catheter Have a confounding medical condition that is progressive and unstable such as HIV, Hepatitis C, active cancer, and/or taking medications for those conditions that are likely to confound the assessment of pre-diabetes Prior surgical operation within the past 6 months Prior injury to the eye involving metallic objects or fragments Prior injury involving a metallic object or foreign body (eg. BB, bullet, shrapnel, etc.) Tattoos from the waist down to the feet Any of the following implants or devices Aneurysm clip Cardiac pacemaker Implanted cardioverter defibrillator (ICD) Electronic implant or device Magnetically activated implant or device Neurostimulation system Spinal cord stimulator Internal electrodes or wires Bone growth/bone fusion stimulator Cochlear, otologic or other ear implant Insulin or other infusion pump Implanted drug infusion device Eye implants Vascular access port and/or catheter Wire mesh implant or stent Other implant Claustrophobia Prior knee replacement surgery Pregnant or intending to become pregnant during the study

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acute Exercise<br>Repeated isometric leg exercises at varying intensities and a second visit with aerobic bike exercise for 30 minutes at 50% peak VO2. | Other: Acute Exercise<br>* Repeated isometric leg exercises at varying intensities for up to twelve minutes per bout. Leg exercises will target the quadriceps muscles.<br>Other: Acute Exercise<br>* Aerobic exercise session on a bike at 50% of peak VO2 for 30 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Acylcarnitine/Carnitine ratio |  | Baseline, One Month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Protein acetylation |  | Baseline, One Month | 
| Change in Insulin Sensitivity |  | Baseline, One Month | 
| Change in Mitochondrial Function |  | Baseline, One Month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Carnitine, Acylcarnitine, Exercise, Exercise Intensity, Insulin Sensitivity