Resistance Training and Testosterone After Spinal Cord Injury

Spinal Cord Injury Clinical Trial

Official title:

Effects of Evoked Resistance Training and Testosterone After Spinal Cord Injury

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01652040
• Other study ID #: B7867-W
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: July 2, 2012
• Est. completion date: December 30, 2017

Study information

• Verified date: May 2018
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this proposal is to investigate the efficacy of a complimentary approach of evoked resistance training and testosterone replacement therapy on the changes in body composition and metabolic profile after SCI. The proposed method could become a recommended and simple intervention especially for individuals with limited access and poor tolerance to exercise. The rationale is based on the evidence that individuals with SCI experience decline in anabolic hormones which may be responsible for the deterioration in body composition and metabolic profiles and leads to increase obesity, type 2 diabetes mellitus, dyslipidemia and subsequently cardiovascular disease. The designed study will provide explanation to the adaptations in the energy source of the muscle cells in response to training.

Description:

Individuals with spinal cord injury (SCI) are at a lifelong risk of increasing obesity and several chronic metabolic disorders such as glucose intolerance, insulin resistance and dyslipidemia secondary to deterioration in body composition. Within few weeks of injury, there are significant decrease in whole body fat-free mass (FFM), particularly lower extremity skeletal muscle mass and subsequent increase in fat mass (FM). Resistance training (RT) is an important type of exercise that has been shown to induce positive physiological adaptations such as increasing lean mass and reducing metabolic disorders in other clinical populations.

In a pilot work, the investigators provided evidence that evoked RT using surface neuromuscular electrical stimulation (NMES) for knee extensor muscle group resulted in significant increase skeletal muscle cross-sectional area (CSA), reduction in % leg FM and a trend towards decrease in visceral adipose tissue (VAT) CSA. The favorable adaptations in body composition were associated with decrease in plasma insulin area under the curve and plasma triglycerides. The investigators attributed the adaptations in body composition and metabolic profile to an associated increase in plasma insulin-like growth factor (IGF-1). The investigators concluded that twelve weeks of evoked RT targeted towards evoking skeletal muscle hypertrophy could result in significant body composition and metabolic adaptations in individuals with SCI.

It is unclear if a longer RT program greater than 12 weeks would provide additional benefits to Veterans with SCI. It is also unknown whether enhancing the decline anabolic homeostasis by providing testosterone (T) replacement therapy (TRT) would reverse body composition and metabolic profile changes in Veterans with SCI. The major research goal of this proposal is to investigate the effects of 16 weeks of evoked RT+TRT vs. TRT on body composition (muscle CSA, VAT, %FM) and the metabolic profiles (glucose and lipid metabolism) in individuals with motor complete SCI. To address this goal, surface NMES accompanied with ankle weights will be conducted twice weekly to exercise the knee extensor skeletal muscle groups from sitting position. After 4 weeks of delayed entry approach, participants (n =24) will be randomly assigned into RT+TRT (n =12) or TRT (n =12) groups. The TRT will be provided via transdermal T patches that will be alternated on both shoulders over the course of the study. The investigators also propose to study the effects of detraining on body composition and metabolic profiles.

The research plan includes three specific aims

Specific aim 1 will demonstrate the effects of NMES RT and/or Testosterone patches (Tp) on the CSA of thighs and legs skeletal muscle groups, percentage FFM, and the CSA of VAT, intramuscular fat and percentage FM after 16 weeks of training+Tp and 16 weeks of detraining.

Specific aim 2 will determine the changes in metabolic milieu (resting energy expenditure, glucose homeostasis, lipid profile, free fatty acids, serum total and free testosterone and IGF-1), and cytokines (c-reactive protein, tumor necrosis factor alpha and IL-6 as inflammatory biomarkers) after 16 weeks of training+Tp and detraining.

Specific aim 3 will determine if 16 weeks of evoked RT and Tp will increase GLUT-4 concentration, muscle IGF-1 and peroxisome-proliferator-activated receptor-gamma co-activator 1 (PGC-1) expressions, altered fiber type distribution and enhance the mitochondrial enzymatic activities (electron transport chain) compared to Tp only.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: December 30, 2017
• Est. primary completion date: December 30, 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Male with Spinal Cord Injury

• Between 18-50 years old

• BMI < 30 Kg/m2

• Traumatic motor complete C5-L2 level of injury

• American Spinal Injury Classification (A and B; i.e. motor deficit below the level of injury)

Exclusion Criteria:

• Cardiovascular disease

• Uncontrolled type II DM and those on insulin

• Pressures sores stage 2 or greater

• Supra-physiological T level

• Hematocrit above 50%

• Urinary tract infection or symptoms

Related Conditions & MeSH terms

• Spinal Cord Injuries
• Spinal Cord Injury
• Wounds and Injuries

Intervention

Device:
• Resistance Training and Testosterone Patches
We are going to activate the knee extensor muscle group to lift ankle weights over 16 weeks and we are going to provide Tp to improve anabolic profile.

Drug:
• Testosterone Patches
The investigators will provide Tp patches for 16 weeks for patients with Spinal Cord Injury.

Locations

Country	Name	City	State
United States	Hunter Holmes McGuire VA Medical Center, Richmond, VA	Richmond	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
VA Office of Research and Development	Virginia Commonwealth University

Country where clinical trial is conducted

United States, 

References & Publications (20)

Abilmona SM, Gorgey AS. Associations of the trunk skeletal musculature and dietary intake to biomarkers of cardiometabolic health after spinal cord injury. Clin Physiol Funct Imaging. 2018 Feb 6. doi: 10.1111/cpf.12505. [Epub ahead of print] — View Citation

Gorgey AS, Caudill C, Khalil RE. Effects of once weekly NMES training on knee extensors fatigue and body composition in a person with spinal cord injury. J Spinal Cord Med. 2016;39(1):99-102. doi: 10.1179/2045772314Y.0000000293. Epub 2015 Jan 23. — View Citation

Gorgey AS, Cirnigliaro CM, Bauman WA, Adler RA. Estimates of the precision of regional and whole body composition by dual-energy x-ray absorptiometry in persons with chronic spinal cord injury. Spinal Cord. 2018 Mar 6. doi: 10.1038/s41393-018-0079-x. [Epub ahead of print] — View Citation

Gorgey AS, Dolbow DR, Cifu DX, Gater DR. Neuromuscular electrical stimulation attenuates thigh skeletal muscles atrophy but not trunk muscles after spinal cord injury. J Electromyogr Kinesiol. 2013 Aug;23(4):977-84. doi: 10.1016/j.jelekin.2013.04.007. Epub 2013 May 15. — View Citation

Gorgey AS, Khalil RE, Gill R, O'Brien LC, Lavis T, Castillo T, Cifu DX, Savas J, Khan R, Cardozo C, Lesnefsky EJ, Gater DR, Adler RA. Effects of Testosterone and Evoked Resistance Exercise after Spinal Cord Injury (TEREX-SCI): study protocol for a randomised controlled trial. BMJ Open. 2017 Apr 4;7(4):e014125. doi: 10.1136/bmjopen-2016-014125. — View Citation

Gorgey AS, Lester RM, Wade RC, Khalil RE, Khan RK, Anderson ML, Castillo T. A feasibility pilot using telehealth videoconference monitoring of home-based NMES resistance training in persons with spinal cord injury. Spinal Cord Ser Cases. 2017 Jun 29;3:17039. doi: 10.1038/scsandc.2017.39. eCollection 2017. — View Citation

Gorgey AS, Mather KJ, Cupp HR, Gater DR. Effects of resistance training on adiposity and metabolism after spinal cord injury. Med Sci Sports Exerc. 2012 Jan;44(1):165-74. doi: 10.1249/MSS.0b013e31822672aa. — View Citation

Gorgey AS, Moore PD, Wade RC, Gill RS, Lavis T, Adler RA. Disruption in bone marrow fat may attenuate testosterone action on muscle size after spinal cord injury: a case report. Eur J Phys Rehabil Med. 2017 Aug;53(4):625-629. doi: 10.23736/S1973-9087.17.04452-5. Epub 2017 Mar 13. — View Citation

Gorgey AS, Shepherd C. Skeletal muscle hypertrophy and decreased intramuscular fat after unilateral resistance training in spinal cord injury: case report. J Spinal Cord Med. 2010;33(1):90-5. — View Citation

Khalil RE, Gorgey AS, Janisko M, Dolbow DR, Moore JR, Gater DR. The role of nutrition in health status after spinal cord injury. Aging Dis. 2013 Feb;4(1):14-22. Epub 2012 Nov 30. — View Citation

McCauley LS, Sumrell RM, Gorgey AS. Anthropometric Prediction of Visceral Adipose Tissue in Persons With Motor Complete Spinal Cord Injury. PM R. 2018 Feb 21. pii: S1934-1482(18)30098-4. doi: 10.1016/j.pmrj.2018.02.007. [Epub ahead of print] — View Citation

Moore PD, Gorgey AS, Wade RC, Khalil RE, Lavis TD, Khan R, Adler RA. Neuromuscular electrical stimulation and testosterone did not influence heterotopic ossification size after spinal cord injury: A case series. World J Clin Cases. 2016 Jul 16;4(7):172-6. doi: 10.12998/wjcc.v4.i7.172. — View Citation

Nightingale TE, Gorgey AS. Predicting Basal Metabolic Rate in Men with Motor Complete Spinal Cord Injury. Med Sci Sports Exerc. 2018 Jan 8. doi: 10.1249/MSS.0000000000001548. [Epub ahead of print] — View Citation

Nightingale TE, Moore P, Harman J, Khalil R, Gill RS, Castillo T, Adler RA, Gorgey AS. Body Composition changes with Testosterone Replacement Therapy following Spinal Cord Injury and Aging. A Mini Review. J Spinal Cord Med. 2017 Aug 3:1-21. doi: 10.1080/10790268.2017.1357917. [Epub ahead of print] — View Citation

O'Brien LC, Chen Q, Savas J, Lesnefsky EJ, Gorgey AS. Skeletal muscle mitochondrial mass is linked to lipid and metabolic profile in individuals with spinal cord injury. Eur J Appl Physiol. 2017 Nov;117(11):2137-2147. doi: 10.1007/s00421-017-3687-9. Epub — View Citation

O'Brien LC, Graham ZA, Chen Q, Lesnefsky EJ, Cardozo C, Gorgey AS. Plasma adiponectin levels are correlated with body composition, metabolic profiles, and mitochondrial markers in individuals with chronic spinal cord injury. Spinal Cord. 2018 Mar 20. doi: 10.1038/s41393-018-0089-8. [Epub ahead of print] — View Citation

O'Brien LC, Wade RC, Segal L, Chen Q, Savas J, Lesnefsky EJ, Gorgey AS. Mitochondrial mass and activity as a function of body composition in individuals with spinal cord injury. Physiol Rep. 2017 Feb;5(3). pii: e13080. doi: 10.14814/phy2.13080. — View Citation

Rankin KC, O'Brien LC, Gorgey AS. Quantification of trunk and android lean mass using dual energy x-ray absorptiometry compared to magnetic resonance imaging after spinal cord injury. J Spinal Cord Med. 2018 Feb 20:1-9. doi: 10.1080/10790268.2018.1438879. [Epub ahead of print] — View Citation

Rankin KC, O'Brien LC, Segal L, Khan MR, Gorgey AS. Liver Adiposity and Metabolic Profile in Individuals with Chronic Spinal Cord Injury. Biomed Res Int. 2017;2017:1364818. doi: 10.1155/2017/1364818. Epub 2017 Aug 30. — View Citation

Wade RC, Gorgey AS. Anthropometric prediction of skeletal muscle cross-sectional area in persons with spinal cord injury. J Appl Physiol (1985). 2017 May 1;122(5):1255-1261. doi: 10.1152/japplphysiol.01042.2016. Epub 2017 Mar 2. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Body Composition	Changes in body composition fat mass	16 weeks
Secondary	Metabolic Profile	Basal Metabolic Rate	16 weeks