Investigating the Effects of Aerobic and Resistance Training in Vivo on Skeletal Muscle Metabolism in Vitro in Primary Human Muscle Cells (MoTrMyo)

NCT04334343 | Active Not Recruiting DMC

• 1 other identifier: 1436585
• Study Type: interventional
• Target: 179
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of the study is to examine the ability of resistance or aerobic exercise training to "imprint" skeletal muscle cells in a manner which confers long-term changes in this tissue which in-turn contribute to improved metabolic health and functional capacity through epigenetic regulation of novel exercise response genes. This study will also provide primary human skeletal muscle cells to the Molecular Transducers of Physical Activity Consortium (MoTrPAC) (NCT03960827) repository for future use.

Conditions

Physical Activity

Outcome Measures

Primary Outcomes (2)

• Mitochondrial function

  Tested via a Analysis of Covariance (ANCOVA) with baseline as covariate followed by post-hoc multiple comparisons.

  Week 12 visit

• Insulin-stimulated glycogen synthesis in human skeletal muscle cell cultures (HSkMC)

  Tested via a Analysis of Covariance (ANCOVA) with baseline as covariate followed by post-hoc multiple comparisons.

  Week 12 visit

Study Arms (3)

Athletic group

ACTIVE COMPARATOR

Other: Additional Muscle Biopsy Collection

Sedentary exercise group

ACTIVE COMPARATOR

Other: Additional Muscle Biopsy Collection

Sedentary no-exercise group

ACTIVE COMPARATOR

Other: Additional Muscle Biopsy Collection

Interventions

Additional Muscle Biopsy Collection OTHER

Subjects will be asked if an additional biopsy from an existing incision can be obtained (i.e. additional needle insertion). For each biopsy required in the main MoTrPAC study (NCT03960827), a small needle will be used to inject some numbing medication (similar to what a dentist uses) in your thigh. A small incision (about 1/4 inch) will be made and a special needle will be used to collect 1 or 2 muscle samples (about the size of a pea).

Athletic group; Sedentary exercise group; Sedentary no-exercise group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willingness to provide informed consent to participate in the MoTrPAC Study
• Willingness to undergo an extra needle insertion for the extra muscle tissue collection during the MoTrPAC muscle biopsy
• Must be able to read and speak English well enough to provide informed consent and understand instructions
• Aged ≥18 y
• Body Mass Index (BMI) \>19 to \<35 kg/m2
• Sedentary defined as self-reporting no more than 1 day per week, lasting no more than 60 minutes, of regular (structured) EE \[e.g., brisk walking, jogging, running, cycling, elliptical, or swimming activity that results in feelings of increased heart rate, rapid breathing, and/or sweating\] or RE (resulting in muscular fatigue) in the past year
• Persons bicycling as a mode of transportation to and from work \>1 day/week etc. are not considered sedentary
• Leisure walkers are included unless they meet the heart rate, breathing, and sweating criteria noted above
• Willingness to provide informed consent to participate in the MoTrPAC Study
• Willingness to undergo an extra needle insertion for the extra muscle tissue collection during the MoTrPAC muscle biopsy
• Must be able to read and speak English well enough to provide informed consent and understand instructions
• Aged ≥18 y
• BMI \>19 to \<35 kg/m2
• Comparator Participants
• Highly Active Endurance Exercise (HAEE): defined as \>240 minutes/week of ET for \>1 year; this can include running, walking (brisk, power), cycling, elliptical, etc. which (at a minimum) results in increased heart rate, rapid breathing and sweating

You may not qualify if:

• Diabetes (self-report and screening tests)
• Treatment with any hypoglycemic agents (self-report) or A1c \>6.4 (screening test; may reassess once if 6.5-6.7)
• Fasting glucose \>125 (screening test; may reassess once)
• Use of hypoglycemic drugs (e.g., metformin) for non-diabetic reasons (self-report)
• Abnormal bleeding or coagulopathy (self-report)
• ◦History of a bleeding disorder or clotting abnormality
• Thyroid disease (screening test)
• Thyroid Stimulating Hormone (TSH) value outside of the normal range for the laboratory
• Individuals with hypothyroidism may be referred to their primary care provider (PCP) for evaluation and retested; any medication change must be stable for ≥3 months prior to retesting
• Individuals with hyperthyroidism are excluded, including those with normal TSH on pharmacologic treatment
• Pulmonary (self-report)
• ◦Clinical diagnosis of Chronic Obstructive Pulmonary Disease (COPD)
• Metabolic bone disease (self-report)
• History of non-traumatic fracture from a standing height or less
• Current pharmacologic treatment for low bone mass or osteoporosis, other than calcium, vitamin D, or estrogen

Sponsors & Collaborators

• AdventHealth Translational Research Institute: lead
• Wake Forest University: collaborator

Study Sites (1)

AdventHealth Translational Research Institute

Orlando, Florida, 32804, United States

Location

Related Publications (19)

• Myers J, Prakash M, Froelicher V, Do D, Partington S, Atwood JE. Exercise capacity and mortality among men referred for exercise testing. N Engl J Med. 2002 Mar 14;346(11):793-801. doi: 10.1056/NEJMoa011858.

  PMID: 11893790 BACKGROUND

• Kokkinos P, Myers J, Kokkinos JP, Pittaras A, Narayan P, Manolis A, Karasik P, Greenberg M, Papademetriou V, Singh S. Exercise capacity and mortality in black and white men. Circulation. 2008 Feb 5;117(5):614-22. doi: 10.1161/CIRCULATIONAHA.107.734764. Epub 2008 Jan 22.

  PMID: 18212278 BACKGROUND

• Egan B, Zierath JR. Exercise metabolism and the molecular regulation of skeletal muscle adaptation. Cell Metab. 2013 Feb 5;17(2):162-84. doi: 10.1016/j.cmet.2012.12.012.

  PMID: 23395166 BACKGROUND

• Reaven GM, Chen YD. Role of abnormal free fatty acid metabolism in the development of non-insulin-dependent diabetes mellitus. Am J Med. 1988 Nov 28;85(5A):106-12. doi: 10.1016/0002-9343(88)90402-0. No abstract available.

  PMID: 3057887 BACKGROUND

• Snijders T, Nederveen JP, McKay BR, Joanisse S, Verdijk LB, van Loon LJ, Parise G. Satellite cells in human skeletal muscle plasticity. Front Physiol. 2015 Oct 21;6:283. doi: 10.3389/fphys.2015.00283. eCollection 2015.

  PMID: 26557092 BACKGROUND

• Ceccarelli G, Benedetti L, Arcari ML, Carubbi C, Galli D. Muscle Stem Cell and Physical Activity: What Point is the Debate at? Open Med (Wars). 2017 Jul 24;12:144-156. doi: 10.1515/med-2017-0022. eCollection 2017.

  PMID: 28765836 BACKGROUND

• Murach KA, Fry CS, Kirby TJ, Jackson JR, Lee JD, White SH, Dupont-Versteegden EE, McCarthy JJ, Peterson CA. Starring or Supporting Role? Satellite Cells and Skeletal Muscle Fiber Size Regulation. Physiology (Bethesda). 2018 Jan 1;33(1):26-38. doi: 10.1152/physiol.00019.2017.

  PMID: 29212890 BACKGROUND

• Boyle KE, Patinkin ZW, Shapiro ALB, Bader C, Vanderlinden L, Kechris K, Janssen RC, Ford RJ, Smith BK, Steinberg GR, Davidson EJ, Yang IV, Dabelea D, Friedman JE. Maternal obesity alters fatty acid oxidation, AMPK activity, and associated DNA methylation in mesenchymal stem cells from human infants. Mol Metab. 2017 Nov;6(11):1503-1516. doi: 10.1016/j.molmet.2017.08.012. Epub 2017 Sep 1.

  PMID: 29107296 BACKGROUND

• Stephens NA, Sparks LM. Resistance to the beneficial effects of exercise in type 2 diabetes: are some individuals programmed to fail? J Clin Endocrinol Metab. 2015 Jan;100(1):43-52. doi: 10.1210/jc.2014-2545.

  PMID: 25412336 BACKGROUND

• Ukropcova B, McNeil M, Sereda O, de Jonge L, Xie H, Bray GA, Smith SR. Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor. J Clin Invest. 2005 Jul;115(7):1934-41. doi: 10.1172/JCI24332.

  PMID: 16007256 BACKGROUND

• Aas V, Bakke SS, Feng YZ, Kase ET, Jensen J, Bajpeyi S, Thoresen GH, Rustan AC. Are cultured human myotubes far from home? Cell Tissue Res. 2013 Dec;354(3):671-82. doi: 10.1007/s00441-013-1655-1. Epub 2013 Jun 8.

  PMID: 23749200 BACKGROUND

• Berggren JR, Tanner CJ, Houmard JA. Primary cell cultures in the study of human muscle metabolism. Exerc Sport Sci Rev. 2007 Apr;35(2):56-61. doi: 10.1249/JES.0b013e31803eae63.

  PMID: 17417051 BACKGROUND

• Gaster M, Kristensen SR, Beck-Nielsen H, Schroder HD. A cellular model system of differentiated human myotubes. APMIS. 2001 Nov;109(11):735-44. doi: 10.1034/j.1600-0463.2001.d01-140.x.

  PMID: 11900052 BACKGROUND

• Ciaraldi TP, Abrams L, Nikoulina S, Mudaliar S, Henry RR. Glucose transport in cultured human skeletal muscle cells. Regulation by insulin and glucose in nondiabetic and non-insulin-dependent diabetes mellitus subjects. J Clin Invest. 1995 Dec;96(6):2820-7. doi: 10.1172/JCI118352.

  PMID: 8675652 BACKGROUND

• Gaster M. Reduced lipid oxidation in myotubes established from obese and type 2 diabetic subjects. Biochem Biophys Res Commun. 2009 May 15;382(4):766-70. doi: 10.1016/j.bbrc.2009.03.102. Epub 2009 Mar 24.

  PMID: 19324004 BACKGROUND

• Lund J, Rustan AC, Lovsletten NG, Mudry JM, Langleite TM, Feng YZ, Stensrud C, Brubak MG, Drevon CA, Birkeland KI, Kolnes KJ, Johansen EI, Tangen DS, Stadheim HK, Gulseth HL, Krook A, Kase ET, Jensen J, Thoresen GH. Exercise in vivo marks human myotubes in vitro: Training-induced increase in lipid metabolism. PLoS One. 2017 Apr 12;12(4):e0175441. doi: 10.1371/journal.pone.0175441. eCollection 2017.

  PMID: 28403174 BACKGROUND

• Bourlier V, Saint-Laurent C, Louche K, Badin PM, Thalamas C, de Glisezinski I, Langin D, Sengenes C, Moro C. Enhanced glucose metabolism is preserved in cultured primary myotubes from obese donors in response to exercise training. J Clin Endocrinol Metab. 2013 Sep;98(9):3739-47. doi: 10.1210/jc.2013-1727. Epub 2013 Jul 24.

  PMID: 23884778 BACKGROUND

• Consitt LA, Bell JA, Koves TR, Muoio DM, Hulver MW, Haynie KR, Dohm GL, Houmard JA. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha overexpression increases lipid oxidation in myocytes from extremely obese individuals. Diabetes. 2010 Jun;59(6):1407-15. doi: 10.2337/db09-1704. Epub 2010 Mar 3.

  PMID: 20200320 BACKGROUND

• Hulver MW, Berggren JR, Carper MJ, Miyazaki M, Ntambi JM, Hoffman EP, Thyfault JP, Stevens R, Dohm GL, Houmard JA, Muoio DM. Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans. Cell Metab. 2005 Oct;2(4):251-61. doi: 10.1016/j.cmet.2005.09.002.

  PMID: 16213227 BACKGROUND

MeSH Terms

Conditions

Motor Activity

Condition Hierarchy (Ancestors)

Behavior

Study Officials

• Lauren Sparks, PhD

  Study Principal Investigator

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2020
• First Posted: April 6, 2020
• Study Start: November 1, 2020
• Primary Completion: January 29, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)