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

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.

Study Overview

• Status: Completed
• Conditions: Elderly; Pre-diabetic
• Intervention / Treatment: Other: Acute Exercise; Other: Acute Exercise

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Center for Living

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acute Exercise; 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; Repeated isometric leg exercises at varying intensities for up to twelve minutes per bout. Leg exercises will target the quadriceps muscles.; Other: Acute Exercise; Aerobic exercise session on a bike at 50% of peak VO2 for 30 minutes.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Pfizer
• Investigators: Principal Investigator: William E Kraus, MD, Duke University

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: April 24, 2014
• First Submitted That Met QC Criteria: April 24, 2014
• First Posted (Estimate): April 28, 2014

Study Record Updates

• Last Update Posted (Estimate): June 17, 2015
• Last Update Submitted That Met QC Criteria: June 15, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: Exercise; Insulin Sensitivity; Exercise Intensity; Carnitine; Acylcarnitine
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Prediabetic State
• Other Study ID Numbers: Pro00053117