Long Duration Activity and Metabolic Control After Spinal Cord Injury

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ClinicalTrials.gov Identifier: NCT03139344

Recruitment Status : Recruiting

First Posted : May 3, 2017

Last Update Posted : June 8, 2018

See Contacts and Locations

Sponsor:

Collaborator:

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Information provided by (Responsible Party):

Richard K Shields, University of Iowa

Study Description

Brief Summary:

Skeletal muscle is the largest endocrine organ in the body, playing an indispensable role in glucose homeostasis. Spinal cord injury (SCI) prevents skeletal muscle from carrying out this important function. Dysregulation of glucose metabolism precipitates high rates of metabolic syndrome, diabetes, and other secondary health conditions (SHCs) of SCI. These SHCs exert a negative influence on health-related quality of life (HRQOL). New discoveries support that a low level of activity throughout the day offers a more effective metabolic stimulus than brief, episodic exercise bouts. The proposed study will translate this emerging concept to the population of individuals with SCI by using low-force, long-duration electrical muscle stimulation to subsidize daily activity levels. Recently, we demonstrated that this type of stimulation up-regulates key genes that foster an oxidative, insulin-sensitive phenotype in paralyzed muscle. We will now test whether this type of activity can improve glucose homeostasis and metabolic function in patients with chronic paralysis. We hypothesize that improvements in metabolic function will be accompanied by a reduction in SHCs and a concomitant improvement in self-reported HRQOL. The long-term goal of this research is to develop a rehabilitation strategy to protect the musculoskeletal health, metabolic function, and health-related quality of life of people living with complete SCI.

Condition or disease	Intervention/treatment	Phase
Spinal Cord Injuries	Other: Low-frequency Exercise Other: High-frequency Exercise	Not Applicable

Study Design


Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	96 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Basic Science
Official Title:	Long Duration Activity and Metabolic Control After Spinal Cord Injury
Actual Study Start Date :	August 1, 2015
Estimated Primary Completion Date :	April 2020
Estimated Study Completion Date :	April 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Exercise and Physical Fitness Spinal Cord Injuries

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Acute gene regulation Adaptations in gene regulation in response to single-session low-frequency exercise or high-frequency exercise.	Other: Low-frequency Exercise The quadriceps/hamstrings will perform exercise via the application of 1 Hz electrical stimulation. Other: High-frequency Exercise The quadriceps/hamstrings will perform exercise via the application of 3 Hz electrical stimulation.
Experimental: Training study Adaptations in gene regulation, systemic metabolic markers, and patient-report metrics in response to training with high-frequency exercise.	Other: High-frequency Exercise The quadriceps/hamstrings will perform exercise via the application of 3 Hz electrical stimulation.

Outcome Measures

Primary Outcome Measures :

Acute gene regulation: NR4A3 [ Time Frame: 3 hours ]
Acute post-stimulation effect upon skeletal muscle nuclear receptor subfamily 4 group A member 3 (NR4A3) expression, measured via muscle biopsy and exon array analysis
Acute gene regulation: PGC1-alpha [ Time Frame: 3 hours ]
Acute post-stimulation effect upon skeletal muscle peroxisome proliferator-activated gamma coactivator (PGC1-alpha) expression, measured via muscle biopsy and exon array analysis
Acute gene regulation: ABRA [ Time Frame: 3 hours ]
Acute post-stimulation effect upon skeletal muscle actin binding Rho activating protein (ABRA) expression, measured via muscle biopsy and exon array analysis
Acute gene regulation: PDK4 [ Time Frame: 3 hours ]
Acute post-stimulation effect upon skeletal muscle pyruvate dehydrogenase kinase 4 (PDK4) expression, measured via muscle biopsy and exon array analysis
Post-training gene regulation: MYH6 [ Time Frame: 6 months ]
Change from baseline in skeletal muscle myosin heavy chain 6 (MYH6) expression, measured via muscle biopsy and exon array analysis
Post-training gene regulation: MYL3 [ Time Frame: 6 months ]
Change from baseline in skeletal muscle myosin light chain 3 (MYL3) expression, measured via muscle biopsy and exon array analysis
Post-training gene regulation: MYH7 [ Time Frame: 6 months ]
Change from baseline in skeletal muscle myosin heavy chain 7 (MYH7) expression, measured via muscle biopsy and exon array analysis
Post-training gene regulation: ACTN3 [ Time Frame: 6 months ]
Change from baseline in skeletal muscle actin 3 (ACTN3) expression, measured via muscle biopsy and exon array analysis
Post-training metabolism: fasting insulin [ Time Frame: 6 months ]
Change from baseline in fasting insulin, measured via venipuncture and standard laboratory assays
Post-training metabolism: fasting glucose [ Time Frame: 6 months ]
Change from baseline in fasting glucose, measured via venipuncture and standard laboratory assays
Post-training subject-report measures: PROMIS Physical health [ Time Frame: 6 months ]
Change from baseline in Patient Reported Outcomes Measurement Information Systems (PROMIS) Global Health - Physical health T-score
Post-training subject-report measures: PROMIS Mental health [ Time Frame: 6 months ]
Change from baseline in Patient Reported Outcomes Measurement Information Systems (PROMIS) Global Health - Mental health T-score

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Motor complete SCI (AIS A-B)

Exclusion Criteria:

Pressure ulcers, chronic infection, lower extremity muscle contractures, deep vein thrombosis, bleeding disorder, recent limb fractures, pregnancy, metformin or other medications for diabetes

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03139344

Contacts


Contact: Richard K Shields, PhD, PT	319-335-9791	richard-shields@uiowa.edu
Contact: Shauna Dudley-Javoroski, PhD, PT	319-356-8203	shauna-dudley@uiowa.edu

Locations


United States, Iowa
University of Iowa	Recruiting
Iowa City, Iowa, United States, 52242

Sponsors and Collaborators

Richard K Shields

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators


Principal Investigator:	Richard K Shields, PhD, PT	University of Iowa

More Information

Publications:

Petrie MA, Suneja M, Faidley E, Shields RK. Low force contractions induce fatigue consistent with muscle mRNA expression in people with spinal cord injury. Physiol Rep. 2014 Feb 25;2(2):e00248. doi: 10.1002/phy2.248. eCollection 2014 Feb 1.

Petrie M, Suneja M, Shields RK. Low-frequency stimulation regulates metabolic gene expression in paralyzed muscle. J Appl Physiol (1985). 2015 Mar 15;118(6):723-31. doi: 10.1152/japplphysiol.00628.2014. Epub 2015 Jan 29.

Petrie MA, Suneja M, Faidley E, Shields RK. A minimal dose of electrically induced muscle activity regulates distinct gene signaling pathways in humans with spinal cord injury. PLoS One. 2014 Dec 22;9(12):e115791. doi: 10.1371/journal.pone.0115791. eCollection 2014.

Petrie MA, Kimball AL, McHenry CL, Suneja M, Yen CL, Sharma A, Shields RK. Distinct Skeletal Muscle Gene Regulation from Active Contraction, Passive Vibration, and Whole Body Heat Stress in Humans. PLoS One. 2016 Aug 3;11(8):e0160594. doi: 10.1371/journal.pone.0160594. eCollection 2016.


Responsible Party:	Richard K Shields, Professor, University of Iowa
ClinicalTrials.gov Identifier:	NCT03139344 History of Changes
Other Study ID Numbers:	201503732 R01HD082109 ( U.S. NIH Grant/Contract )
First Posted:	May 3, 2017 Key Record Dates
Last Update Posted:	June 8, 2018
Last Verified:	May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No


Studies a U.S. FDA-regulated Drug Product:		No
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Richard K Shields, University of Iowa:


metabolism exercise glucose secondary health conditions quality of life

Additional relevant MeSH terms:


Wounds and Injuries Spinal Cord Injuries Spinal Cord Diseases	Central Nervous System Diseases Nervous System Diseases Trauma, Nervous System

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