Long Duration Activity and Metabolic Control After Spinal Cord Injury

NCT ID: NCT03139344

Last Updated: 2023-02-16

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

89 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-08-01

Study Completion Date

2022-04-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Skeletal muscle is a critical organ for regulating glucose and insulin in the body as a whole, and post-spinal cord injury (SCI) adaptations in muscle severely undermine this capacity. Contemporary SCI rehabilitation for people with complete SCI does not intervene to protect the function of paralyzed skeletal muscle as a key regulator of metabolic homeostasis. Through its deleterious effects on multiple systems, metabolic disease is one of the leading sources of morbidity, mortality, and health care cost for this population.

In the non-SCI population, pervasive, frequent, low-magnitude muscle contractions can increase energy expenditure by 50.3% above sitting levels. The loss of this component of muscle activity contributes to the energy imbalance and metabolic dysregulation observed in SCI. Subsidizing low-magnitude muscle contractions may offer an important metabolic stimulus for people with SCI. The significance of this study is that it builds on previous work demonstrating healthful transcriptional and translational gene adaptations in response to electrical stimulation training in SCI. These adaptations may initiate improvements in systemic biomarkers of metabolic health and improvements in secondary health conditions and health-related quality of life.

In our previous work, we demonstrated that regular electrical stimulation of paralyzed muscle up-regulates PGC-1α, a key transcriptional co-activator for skeletal muscle and metabolic adaptation. Our previous work also indicates that electrical stimulation alters the expression of genes controlling mitochondrial biogenesis. However, we understand very little about the optimal amount of electrically-evoked muscle activity to deliver in order to promote positive metabolic adaptations. Long duration, low force contractions are likely to be most advantageous for promoting metabolic stability in people with chronic SCI, who also have osteoporosis and are unable to receive high force muscle contractions induced by conventional rehabilitation protocols. This study will intervene with a protocol of low-force, long-duration muscle stimulation designed to instigate systemic metabolic adaptations. In the proposed study we hypothesize that gene-level adaptations will yield tissue-level improvements in glucose utilization that facilitate systemic improvements in clinical markers of metabolic control, culminating in fewer secondary health conditions and enhanced health-related quality of life.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Spinal Cord Injuries

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Acute gene regulation: low frequency

Adaptations in gene regulation in response to single-session low-frequency exercise.

Group Type EXPERIMENTAL

Low-frequency Exercise

Intervention Type OTHER

The quadriceps/hamstrings will perform exercise via the application of low-frequency electrical stimulation.

Acute gene regulation: high frequency

Adaptations in gene regulation in response to single-session high-frequency exercise.

Group Type EXPERIMENTAL

High-frequency Exercise

Intervention Type OTHER

The quadriceps/hamstrings will perform exercise via the application of high-frequency electrical stimulation.

Training study: low frequency

Adaptations in gene regulation, systemic metabolic markers, and patient-report metrics in response to training with low-frequency exercise.

Group Type EXPERIMENTAL

Low-frequency Exercise

Intervention Type OTHER

The quadriceps/hamstrings will perform exercise via the application of low-frequency electrical stimulation.

Training study: high frequency

Adaptations in gene regulation in response to training with high-frequency exercise.

Group Type EXPERIMENTAL

High-frequency Exercise

Intervention Type OTHER

The quadriceps/hamstrings will perform exercise via the application of high-frequency electrical stimulation.

Comparator cohort

Participants will undergo selected outcome measures to provide comparison values for Experimental arms.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Low-frequency Exercise

The quadriceps/hamstrings will perform exercise via the application of low-frequency electrical stimulation.

Intervention Type OTHER

High-frequency Exercise

The quadriceps/hamstrings will perform exercise via the application of high-frequency electrical stimulation.

Intervention Type OTHER

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

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

NIH

Sponsor Role collaborator

Richard K Shields

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Richard K Shields

Professor

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Richard K Shields, PhD, PT

Role: PRINCIPAL_INVESTIGATOR

University of Iowa

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University of Iowa

Iowa City, Iowa, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Dudley-Javoroski S, Saha PK, Liang G, Li C, Gao Z, Shields RK. High dose compressive loads attenuate bone mineral loss in humans with spinal cord injury. Osteoporos Int. 2012 Sep;23(9):2335-46. doi: 10.1007/s00198-011-1879-4. Epub 2011 Dec 21.

Reference Type BACKGROUND
PMID: 22187008 (View on PubMed)

Dudley-Javoroski S, Shields RK. Dose estimation and surveillance of mechanical loading interventions for bone loss after spinal cord injury. Phys Ther. 2008 Mar;88(3):387-96. doi: 10.2522/ptj.20070224. Epub 2008 Jan 17.

Reference Type BACKGROUND
PMID: 18202080 (View on PubMed)

Dudley-Javoroski S, Shields RK. Active-resisted stance modulates regional bone mineral density in humans with spinal cord injury. J Spinal Cord Med. 2013 May;36(3):191-9. doi: 10.1179/2045772313Y.0000000092.

Reference Type BACKGROUND
PMID: 23809588 (View on PubMed)

Dudley-Javoroski S, Littmann AE, Iguchi M, Shields RK. Doublet stimulation protocol to minimize musculoskeletal stress during paralyzed quadriceps muscle testing. J Appl Physiol (1985). 2008 Jun;104(6):1574-82. doi: 10.1152/japplphysiol.00892.2007. Epub 2008 Apr 24.

Reference Type BACKGROUND
PMID: 18436697 (View on PubMed)

Dudley-Javoroski S, Shields RK. Assessment of physical function and secondary complications after complete spinal cord injury. Disabil Rehabil. 2006 Jan 30;28(2):103-10. doi: 10.1080/09638280500163828.

Reference Type BACKGROUND
PMID: 16393840 (View on PubMed)

Adams CM, Suneja M, Dudley-Javoroski S, Shields RK. Altered mRNA expression after long-term soleus electrical stimulation training in humans with paralysis. Muscle Nerve. 2011 Jan;43(1):65-75. doi: 10.1002/mus.21831.

Reference Type BACKGROUND
PMID: 21171097 (View on PubMed)

Frey Law LA, Shields RK. Femoral loads during passive, active, and active-resistive stance after spinal cord injury: a mathematical model. Clin Biomech (Bristol). 2004 Mar;19(3):313-21. doi: 10.1016/j.clinbiomech.2003.12.005.

Reference Type BACKGROUND
PMID: 15003348 (View on PubMed)

Kunkel SD, Suneja M, Ebert SM, Bongers KS, Fox DK, Malmberg SE, Alipour F, Shields RK, Adams CM. mRNA expression signatures of human skeletal muscle atrophy identify a natural compound that increases muscle mass. Cell Metab. 2011 Jun 8;13(6):627-38. doi: 10.1016/j.cmet.2011.03.020.

Reference Type BACKGROUND
PMID: 21641545 (View on PubMed)

McHenry CL, Wu J, Shields RK. Potential regenerative rehabilitation technology: implications of mechanical stimuli to tissue health. BMC Res Notes. 2014 Jun 3;7:334. doi: 10.1186/1756-0500-7-334.

Reference Type BACKGROUND
PMID: 24894666 (View on PubMed)

McHenry CL, Shields RK. A biomechanical analysis of exercise in standing, supine, and seated positions: Implications for individuals with spinal cord injury. J Spinal Cord Med. 2012 May;35(3):140-7. doi: 10.1179/2045772312Y.0000000011.

Reference Type BACKGROUND
PMID: 22507023 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25531450 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24744911 (View on PubMed)

Shields RK, Dudley-Javoroski S. Monitoring standing wheelchair use after spinal cord injury: a case report. Disabil Rehabil. 2005 Feb 4;27(3):142-6. doi: 10.1080/09638280400009337.

Reference Type BACKGROUND
PMID: 15823996 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25635001 (View on PubMed)

Zhorne R, Dudley-Javoroski S, Shields RK. Skeletal muscle activity and CNS neuro-plasticity. Neural Regen Res. 2016 Jan;11(1):69-70. doi: 10.4103/1673-5374.169623. No abstract available.

Reference Type BACKGROUND
PMID: 26981083 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27486743 (View on PubMed)

Shields RK. Turning Over the Hourglass. Phys Ther. 2017 Oct 1;97(10):949-963. doi: 10.1093/ptj/pzx072.

Reference Type BACKGROUND
PMID: 29029555 (View on PubMed)

Woelfel JR, Kimball AL, Yen CL, Shields RK. Low-Force Muscle Activity Regulates Energy Expenditure after Spinal Cord Injury. Med Sci Sports Exerc. 2017 May;49(5):870-878. doi: 10.1249/MSS.0000000000001187.

Reference Type BACKGROUND
PMID: 28009786 (View on PubMed)

Yen CL, McHenry CL, Petrie MA, Dudley-Javoroski S, Shields RK. Vibration training after chronic spinal cord injury: Evidence for persistent segmental plasticity. Neurosci Lett. 2017 Apr 24;647:129-132. doi: 10.1016/j.neulet.2017.03.019. Epub 2017 Mar 16.

Reference Type BACKGROUND
PMID: 28315725 (View on PubMed)

Oza PD, Dudley-Javoroski S, Shields RK. Modulation of H-Reflex Depression with Paired-Pulse Stimulation in Healthy Active Humans. Rehabil Res Pract. 2017;2017:5107097. doi: 10.1155/2017/5107097. Epub 2017 Oct 31.

Reference Type BACKGROUND
PMID: 29225972 (View on PubMed)

Woelfel JR, Dudley-Javoroski S, Shields RK. Precision Physical Therapy: Exercise, the Epigenome, and the Heritability of Environmentally Modified Traits. Phys Ther. 2018 Nov 1;98(11):946-952. doi: 10.1093/ptj/pzy092.

Reference Type BACKGROUND
PMID: 30388254 (View on PubMed)

Cole KR, Dudley-Javoroski S, Shields RK. Hybrid stimulation enhances torque as a function of muscle fusion in human paralyzed and non-paralyzed skeletal muscle. J Spinal Cord Med. 2019 Sep;42(5):562-570. doi: 10.1080/10790268.2018.1485312. Epub 2018 Jun 20.

Reference Type BACKGROUND
PMID: 29923814 (View on PubMed)

Dudley-Javoroski S, Lee J, Shields RK. Cognitive function, quality of life, and aging: relationships in individuals with and without spinal cord injury. Physiother Theory Pract. 2022 Jan;38(1):36-45. doi: 10.1080/09593985.2020.1712755. Epub 2020 Jan 8.

Reference Type BACKGROUND
PMID: 31914347 (View on PubMed)

Petrie MA, Sharma A, Taylor EB, Suneja M, Shields RK. Impact of short- and long-term electrically induced muscle exercise on gene signaling pathways, gene expression, and PGC1a methylation in men with spinal cord injury. Physiol Genomics. 2020 Feb 1;52(2):71-80. doi: 10.1152/physiolgenomics.00064.2019. Epub 2019 Dec 23.

Reference Type BACKGROUND
PMID: 31869286 (View on PubMed)

Lee J, Dudley-Javoroski S, Shields RK. Motor demands of cognitive testing may artificially reduce executive function scores in individuals with spinal cord injury. J Spinal Cord Med. 2021 Mar;44(2):253-261. doi: 10.1080/10790268.2019.1597482. Epub 2019 Apr 3.

Reference Type BACKGROUND
PMID: 30943119 (View on PubMed)

Shields RK. Precision Rehabilitation: How Lifelong Healthy Behaviors Modulate Biology, Determine Health, and Affect Populations. Phys Ther. 2022 Jan 1;102(1):pzab248. doi: 10.1093/ptj/pzab248. No abstract available.

Reference Type BACKGROUND
PMID: 34718793 (View on PubMed)

Shields RK, Dudley-Javoroski S. Epigenetics and the International Classification of Functioning, Disability and Health Model: Bridging Nature, Nurture, and Patient-Centered Population Health. Phys Ther. 2022 Jan 1;102(1):pzab247. doi: 10.1093/ptj/pzab247.

Reference Type BACKGROUND
PMID: 34718813 (View on PubMed)

Petrie MA, Taylor EB, Suneja M, Shields RK. Genomic and Epigenomic Evaluation of Electrically Induced Exercise in People With Spinal Cord Injury: Application to Precision Rehabilitation. Phys Ther. 2022 Jan 1;102(1):pzab243. doi: 10.1093/ptj/pzab243.

Reference Type BACKGROUND
PMID: 34718779 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

R01HD082109

Identifier Type: NIH

Identifier Source: secondary_id

View Link

201503732

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Carbohydrate Study, Chronic SCI
NCT00786435 COMPLETED
Retraining Walking After Spinal Cord Injury
NCT00059553 UNKNOWN PHASE2/PHASE3