Metabolic Inflexibility is Related to Elevated Muscle Anaerobic Glycolysis

NCT04320264 | Recruiting

• 1 other identifier: UMCIRB 19-000914
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The focus of this proposal is on overweight (25\>BMI\<30 kg/m2) subjects, as these individuals exhibit a high risk of becoming obese and/or developing metabolic diseases. We hypothesize that in some overweight individuals there is a "metabolic program" in skeletal muscle which predisposes them to the development of obesity. Findings may lead to clinical screening tools for determining risk for obesity in non-obese individuals and targeting this group for prevention.

Conditions

Metabolic Inflexibility

Keywords

Metabolic Inflexibility; Obesity; Anaerobic glycolysis

Outcome Measures

Primary Outcomes (6)

• Carbohydrate/fat oxidation (RER) in the fasting condition.

  RER will be measured from indirect calorimetry

  Years 1-5

• Muscle oxygen consumption (substrate oxidation) in the fasting condition.

  Muscle oxygen consumption will be measured by near-infrared spectroscopy (NIRS)

  Years 1-5

• Muscle lactate release in the fasting condition.

  Muscle lactate release will be measured by microdialysis

  Years 1-5

• Change in Carbohydrate/fat oxidation (RER) in response to glucose + insulin (metabolic flexibility)

  Indirect calorimetry during glucose clamp

  Years 1-5

• Change in muscle fat oxidation in response to high fat feeding (metabolic flexibility).

  Oxidation of fatty acid in muscle homogenate.

  Years 1-5

• Change in muscle oxygen consumption (substrate oxidation) in response to high fat feeding (metabolic flexibility).

  Oxygen consumption measured by near-infrared spectroscopy (NIRS)

  Years 1-5

Secondary Outcomes (2)

• Insulin sensitivity (clamp M value).

  Years 1-5

• Endogenous glucose production in the fasting condition.

  Years 1-5

Study Arms (3)

Low oxidizers/high lactate

Individuals with low aerobic oxidation

High oxidizers/low lactate

Individuals with high aerobic oxidation

Obese

Severely obese scheduled for surgery

Procedure: Weight loss surgery

Interventions

Weight loss surgery PROCEDURE

Severely obese women (BMI \>40) undergo sleeve gastrectomy

Obese

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

High oxidizers Low oxidizers Obese

You may qualify if:

• years old
• BMI of 25 - 30 kg/m2
• BMI \> 40kg/m2
• Lactate levels in top and lower 25%

You may not qualify if:

• Pregnant women
• Mentally disabled
• Prisoners
• Smokers
• Subjects with heart disease
• Type 1 and 2 diabetes
• Endocrine disease
• Hypertension
• Musculoskeletal disease
• Peripheral occlusion
• Hepatic disease
• Have had weight fluctuations exceeding + 3% in the previous 12 months
• On medications which alter carbohydrate metabolism will not be studied

Sponsors & Collaborators

• East Carolina University: lead
• Duke University: collaborator
• University of Arkansas: collaborator

Study Sites (1)

East Carolina University

Greenville, North Carolina, 27834, United States

RECRUITING

Related Publications (5)

• Ryan TE, Brophy P, Lin CT, Hickner RC, Neufer PD. Assessment of in vivo skeletal muscle mitochondrial respiratory capacity in humans by near-infrared spectroscopy: a comparison with in situ measurements. J Physiol. 2014 Aug 1;592(15):3231-41. doi: 10.1113/jphysiol.2014.274456. Epub 2014 Jun 20.

  PMID: 24951618 BACKGROUND

• Camisa C, Rossana C. Variant of keratoderma hereditaria mutilans (Vohwinkel's syndrome). Treatment with orally administered isotretinoin. Arch Dermatol. 1984 Oct;120(10):1323-8.

  PMID: 6237617 BACKGROUND

• Craglietto T, Giarelli L, Paolini A. [Comparative study of the DNA content of human female breast adenocarcinomas and of their recurrences. (Histo-spectrophotometric findings)]. Riv Anat Patol Oncol. 1964 Nov-Dec;26(5):694-706. No abstract available. Italian.

  PMID: 5866193 BACKGROUND

• Ciresa M, Gabl F, Knapp E. [Acid-base equilibrium]. Wien Klin Wochenschr. 1970 Jan 2;82(1):11-2. No abstract available. German.

  PMID: 5513193 BACKGROUND

• Iwamasa J, Tajima C, Matsuura K, Okamura H. [Role of progesterone in the ovulatory process of PMSG/hCG treated immature female rats]. Nihon Sanka Fujinka Gakkai Zasshi. 1989 Oct;41(10):1551-6. Japanese.

  PMID: 2584808 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood and tissue samples without analysis of DNA

MeSH Terms

Conditions

Obesity

Interventions

Bariatric Surgery

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Bariatrics; Obesity Management; Therapeutics; Surgical Procedures, Operative

Study Officials

• Joseph Houmard, PhD

  East Carolina University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Terry Jones, PhD

CONTACT

2527446249; joneste@ecu.edu

Nicholas Broskey, PhD

CONTACT

2527374684; broskeyn19@ecu.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2019
• First Posted: March 24, 2020
• Study Start: March 3, 2020
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: August 7, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)