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Study of Changes in Skeletal Muscle After Caloric Restriction

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
Charles R. Flynn, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00993460
First received: October 7, 2009
Last updated: November 19, 2012
Last verified: November 2012
History of Changes
  Purpose

Research has shown that fat stored within muscles affects the muscle's sensitivity to insulin and ability to handle blood glucose. The purpose of this study is to examine the effects of weight loss surgery-induced caloric restriction on the accumulation and types of fats within skeletal muscle, as well as the effects of such caloric restriction on insulin sensitivity and inflammatory responses in skeletal muscle. The investigator proposes that caloric restriction will result in decreases in diacylglycerols enriched with saturated fat and increases in diacylglycerols enriched with monounsaturated fats.


Condition
Obesity

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Diacylglycerols and Insulin Action in Skeletal Muscle Upon Caloric Restriction

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • UPLC-ESI MS/MS profiling of lipd extracts from muscle biopsies to evaluate effects of gastric bypass induced-caloric restriction on diacylglycerol molecular species accumulation. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the effects of gastric bypass induced-caloric restriction on skeletal muscle insulin action via a hyperinsulinemic-euglycemic clamp and profiling markers of insulin signaling. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • To evaluate the effects of gastric bypass induced-caloric restriction on lipid-mediated inflammatory responses by profiling cytokines and free fatty acids in blood and inflammation markers in skeletal muscle biopsies. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Whole blood, plasma, muscle tissue


Estimated Enrollment: 24
Study Start Date: March 2011
Estimated Study Completion Date: November 2013
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
Normal body weight
Female subjects, ages 21-65 yrs, with BMI of 21-27 kg/m2 with normal glucose tolerance.
Roux-en-Y gastric bypass
Female subjects ages 21-65 with insulin resistance and scheduled for Roux-en-Y gastric bypass at Vanderbilt University Medical Center will be studied before and 4-6 weeks after surgery.

Detailed Description:

We hypothesize that in a setting of surgically-induced weight loss decrements in select DAGs result in improved glucose utilization, altered insulin signaling and decreased inflammatory responses. We propose to examine the impact of molecular DAG species accumulation on glucose utilization, insulin signaling and inflammation in skeletal muscle from morbidly obese subjects before/after 10% weight loss facilitated by Roux-en-Y Gastric Bypass (RYGB). We will compare these results to those from a control, normal weight cohort

The detected differences in DAG molecular species, insulin action, inflammatory responses between normal and obese subjects (before/after weight loss) will emphasize pathways coordinately altered as a consequence of adiposity and RYGB surgery. The primary endpoints for this study will be: Insulin sensitivity (glucose Rd, insulin levels, DAG mass, DAG species amounts).Secondary endpoints will be: FFA levels, inflammatory cytokine production, and insulin signaling in skeletal muscle.

  Eligibility

Ages Eligible for Study:   21 Years to 65 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Female subjects approved for Roux-en-Y gastric bypass surgery at Vanderbilt University Medical Center.

Criteria

Inclusion Criteria:

  • For Normal Weight Subjects:

    • Age 21-65 years
    • BMI of 21 to 27 kg/m2
    • Normal glucose tolerance as determined by OGTT on day of screening
    • No family history of diabetes

  • For Morbidly Obese Subjects:

    • Age 21-65 years
    • BMI of 30 to 65 kg/m2
    • Scheduled for Roux-en-Y gastric bypass at Vanderbilt Medical Center
    • Insulin resistant as determined by OGTT on day of screening

Exclusion Criteria (for all subjects):

  • Clinically significant heart disease
  • Clinically significant hepatic or renal disease
  • Pregnancy
  • Breastfeeding
  • Any abnormality that would preclude safe completion of study
  • Use of statins
  • Use of thiazide or furosemide diuretics, beta blockers, or other chronic medications with known adverse effects on glucose tolerance levels unless subject has been on stable dose of such medications for the past 3 months before entering the study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00993460

Locations
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Charles R Flynn, PhD Vanderbilt University
Study Chair: Naji Abumrad, MD Vanderbilt University
  More Information

No publications provided

Responsible Party: Charles R. Flynn, Assistant Professor, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00993460     History of Changes
Other Study ID Numbers: IRB #091145
Study First Received: October 7, 2009
Last Updated: November 19, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
Obesity
Insulin sensitivity
Inflammation

Additional relevant MeSH terms:
Obesity
Overnutrition
Nutrition Disorders
 Overweight
Body Weight
Signs and Symptoms

ClinicalTrials.gov processed this record on May 23, 2013