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Lumbar Spine Muscle Degeneration Inhibits Rehabilitation-Induced Muscle Recovery

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ClinicalTrials.gov Identifier: NCT03442374
Recruitment Status : Not yet recruiting
First Posted : February 22, 2018
Last Update Posted : June 11, 2019
Sponsor:
Collaborators:
University of Zurich, Balgrist Hospital
Spine Institute of San Diego (Spine Zone)
Information provided by (Responsible Party):
Samuel R. Ward, University of California, San Diego

Brief Summary:
Low back pain (LBP) is a complex condition that affects 65-85% of the population, and is the leading musculoskeletal condition contributing to disability in the United States. Disc herniation is the most common injury and 75% of individuals undergoing surgical and rehabilitative interventions for this condition experience suboptimal or poor outcomes. These patients demonstrate disability and deficits in functional capacity, including strength and endurance of the lumbar musculature. Muscle-specific changes in individuals with LBP include altered muscle volume, fatty infiltration and fibrosis, and fiber area and type. Importantly, these changes are insensitive to rehabilitation in patients with continued chronic or recurrent symptoms. While normal disuse-related atrophy in the presence of LBP is expected, more severe or chronic pathology, such as inflammation and fiber damage, may be inducing irreversible fiber degeneration and fatty/fibrotic tissue changes that impair muscle function and recovery. While the structural and adaptive capacities of healthy muscle are well understood, muscle recovery in the presence of pathology is less clear. To address this gap in knowledge, the purpose of this project is to compare structural, physiological, and adaptive responses of muscle in the presence of acute and chronic lumbar spine pathology. The central hypothesis is that chronic injury results in a state of muscle inflammation, atrophy, fibrosis, and muscle degeneration that is not responsive to exercise. The Investigators will identify which patients respond to exercise by examining muscle hypertrophic, fibrotic, inflammatory, and adipogenic gene expression profiles. Patients will be followed for six months post-operatively to measure muscle recovery and strength.

Condition or disease Intervention/treatment Phase
Disc Degeneration Low Back Pain Other: Exercise Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Stratified by fatty infiltration severity (n=20/group x 2 groups + non exercise controls n=20)
Masking: Single (Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Lumbar Spine Muscle Degeneration Inhibits Rehabilitation-Induced Muscle
Estimated Study Start Date : July 2019
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Exercise
A single bout of moderate intensity lumbar extensor muscle exercise.
Other: Exercise
The exercise protocol consists of 1 set of 20 repetitions (range 15-25 reps) at a rate of 5 seconds/repetitions with a starting weight of 60-80% of their computerized strength score. Patients will be instructed to target an exertion level of 7/10 on the Borg Rate of Perceived Exertion (RPE) scale within their available passive ROM range into flexion-extension

No Intervention: Non-exercise
No exercise intervention.



Primary Outcome Measures :
  1. Change in Multifidus Muscle Fatty Infiltration [ Time Frame: 6 months ]
    (% fat at 6 months - % fat at baseline / % fat at baseline)


Secondary Outcome Measures :
  1. Change in Oswestry Disability Index (ODI) [ Time Frame: 6 Months ]
    Disability Questionnaire (10 questions, % scale is sum of 10 questions/50, higher score is worse), 6 months - baseline

  2. Change in Fear Avoidance Beliefs Questionnaire (FABQ) [ Time Frame: 6 months ]
    Fear Avoidance Behaviors (sumo 16 items, 0-64 scale, higher score is worse), 6 months- baseline

  3. Change in Pain Catastrophizing Scale (PCS) [ Time Frame: 6 months ]
    Pain behaviors questionnaire (sum of 13 items, 0-52 scale, higher score is worse), 6 months - baseline

  4. Change in Activated Muscle Volume (%) [ Time Frame: After exercise (within 5 minutes) ]
    (% muscle activation after exercise - % muscle activation at baseline / % muscle activation at baseline)

  5. Change in Pain (VAS) [ Time Frame: 6 months ]
    Visual Analog Scale (0-100 mm scale), 6 months - baseline

  6. Change in Strength [ Time Frame: 6 months ]
    MedEx dynamometer, Back Extensor Strength (Nm), 6 months - baseline

  7. MYHC3 gene expression (delta CT/delta CT) [ Time Frame: 6 hours after a single exercise bout ]
    Embryonic myosin heavy chain gene expression

  8. MHY3 protein abundance (ug/mg) [ Time Frame: 6 hours after a single exercise bout ]
    Embryonic myosin heavy chain protein abundance

  9. MYOG gene expression (delta CT/delta CT) [ Time Frame: 6 hours after a single exercise bout ]
    Myogenin gene expression

  10. MYOG protein abundance (ug/mg) [ Time Frame: 6 hours after a single exercise bout ]
    Myogenin protein abundance

  11. PAX7 gene expression (delta CT/delta CT) [ Time Frame: 6 hours after a single exercise bout ]
    PAX7 gene expression

  12. PAX7 gene expression (ug/mg) [ Time Frame: 6 hours after a single exercise bout ]
    PAX7 protein abundance

  13. ANKRD2 gene expression (delta CT/delta CT) [ Time Frame: 6 hours after a single exercise bout ]
    ANKRD2 gene expression

  14. ANKRD2 protein abundance (ug/mg) [ Time Frame: 6 hours after a single exercise bout ]
    ANKRD2 protein abundance

  15. MTOR gene expression (delta CT/delta CT) [ Time Frame: 6 hours after a single exercise bout ]
    MTOR gene expression

  16. MTOR protein abundance (ug/mg) [ Time Frame: 6 hours after a single exercise bout ]
    MTOR protein abundance

  17. COL1A1 gene expression (delta CT/delta CT) [ Time Frame: 6 hours after a single exercise bout ]
    COL1A1 gene expression

  18. COL3A1 gene expression (delta CT/delta CT) [ Time Frame: 6 hours after a single exercise bout ]
    COL3A1 gene expression

  19. COL9A1 gene expression (delta CT/delta CT) [ Time Frame: 6 hours after a single exercise bout ]
    COL9A1 gene expression

  20. LOX gene expression (delta CT/delta CT) [ Time Frame: 6 hours after a single exercise bout ]
    LOX gene expression

  21. CTGF gene expression (delta CT/delta CT) [ Time Frame: 6 hours after a single exercise bout ]
    CTGF gene expression

  22. TGFB1 gene expression (delta CT/delta CT) [ Time Frame: 6 hours after a single exercise bout ]
    TGFB1 gene expression

  23. MMP1 gene expression (delta CT/delta CT) [ Time Frame: 6 hours after a single exercise bout ]
    MMP1 gene expression

  24. MMP3 gene expression (delta CT/delta CT) [ Time Frame: 6 hours after a single exercise bout ]
    MMP3 gene expression

  25. MMP9 gene expression (delta CT/delta CT) [ Time Frame: 6 hours after a single exercise bout ]
    MMP9 gene expression

  26. CEBPA gene expression (delta CT/delta CT) [ Time Frame: 6 hours after a single exercise bout ]
    CEBPA gene expression

  27. FABP4 gene expression (delta CT/delta CT) [ Time Frame: 6 hours after a single exercise bout ]
    FABP4 gene expression

  28. PPARG gene expression (delta CT/delta CT) [ Time Frame: 6 hours after a single exercise bout ]
    PPARG gene expression

  29. PPARD gene expression (delta CT/delta CT) [ Time Frame: 6 hours after a single exercise bout ]
    PPARD gene expression

  30. LEP gene expression (delta CT/delta CT) [ Time Frame: 6 hours after a single exercise bout ]
    LEP gene expression

  31. ADIPOQ gene expression (delta CT/delta CT) [ Time Frame: 6 hours after a single exercise bout ]
    ADIPOQ gene expression

  32. CASP1 gene expression (delta CT/delta CT) [ Time Frame: 6 hours after a single exercise bout ]
    CASP1 gene expression

  33. CASP3 gene expression (delta CT/delta CT) [ Time Frame: 6 hours after a single exercise bout ]
    CASP3 gene expression

  34. TNFa gene expression (delta CT/delta CT) [ Time Frame: 6 hours after a single exercise bout ]
    TNFa gene expression

  35. IL10 gene expression (delta CT/delta CT) [ Time Frame: 6 hours after a single exercise bout ]
    IL10 gene expression

  36. IL6 gene expression (delta CT/delta CT) [ Time Frame: 6 hours after a single exercise bout ]
    IL6 gene expression

  37. IL1B gene expression (delta CT/delta CT) [ Time Frame: 6 hours after a single exercise bout ]
    IL1B gene expression

  38. COL1A1 Protein abundance (ug/mg) [ Time Frame: 6 hours after a single exercise bout ]
    COL1A1 Protein abundance

  39. COL3A1 Protein abundance (ug/mg) [ Time Frame: 6 hours after a single exercise bout ]
    COL3A1 Protein abundance

  40. COL9A1 Protein abundance (ug/mg) [ Time Frame: 6 hours after a single exercise bout ]
    COL9A1 Protein abundance

  41. LOX Protein abundance (ug/mg) [ Time Frame: 6 hours after a single exercise bout ]
    LOX Protein abundance

  42. CTGF Protein abundance (ug/mg) [ Time Frame: 6 hours after a single exercise bout ]
    CTGF Protein abundance

  43. TGFB1 Protein abundance (ug/mg) [ Time Frame: 6 hours after a single exercise bout ]
    TGFB1 Protein abundance

  44. MMP1 Protein abundance (ug/mg) [ Time Frame: 6 hours after a single exercise bout ]
    MMP1 Protein abundance

  45. MMP3 Protein abundance (ug/mg) [ Time Frame: 6 hours after a single exercise bout ]
    MMP3 Protein abundance

  46. MMP9 Protein abundance (ug/mg) [ Time Frame: 6 hours after a single exercise bout ]
    MMP9 Protein abundance

  47. CEBPA Protein abundance (ug/mg) [ Time Frame: 6 hours after a single exercise bout ]
    CEBPA Protein abundance

  48. FABP4 Protein abundance (ug/mg) [ Time Frame: 6 hours after a single exercise bout ]
    FABP4 Protein abundance

  49. PPARG Protein abundance (ug/mg) [ Time Frame: 6 hours after a single exercise bout ]
    PPARG Protein abundance

  50. PPARD Protein abundance (ug/mg) [ Time Frame: 6 hours after a single exercise bout ]
    PPARD Protein abundance

  51. LEP Protein abundance (ug/mg) [ Time Frame: 6 hours after a single exercise bout ]
    LEP Protein abundance

  52. ADIPOQ Protein abundance (ug/mg) [ Time Frame: 6 hours after a single exercise bout ]
    ADIPOQ Protein abundance

  53. CASP1 Protein abundance (ug/mg) [ Time Frame: 6 hours after a single exercise bout ]
    CASP1 Protein abundance

  54. CASP3 Protein abundance (ug/mg) [ Time Frame: 6 hours after a single exercise bout ]
    CASP3 Protein abundance

  55. TNFa Protein abundance (ug/mg) [ Time Frame: 6 hours after a single exercise bout ]
    TNFa Protein abundance

  56. IL10 Protein abundance (ug/mg) [ Time Frame: 6 hours after a single exercise bout ]
    IL10 Protein abundance

  57. IL6 Protein abundance (ug/mg) [ Time Frame: 6 hours after a single exercise bout ]
    IL6 Protein abundance

  58. IL1B Protein abundance (ug/mg) [ Time Frame: 6 hours after a single exercise bout ]
    IL1B Protein abundance

  59. Change in Multifidus muscle volume (%) [ Time Frame: baseline ]
    Multifidus muscle volume (cc), (6 months - baseline/baseline)



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Spine pathologies requiring un-instrumented surgery (i.e. laminectomy, laminoforaminotomy, or discectomy).
  • Age 21-85 years of age.

Exclusion Criteria:

  • History of lumbar spine surgery.
  • Patients requiring placement of instrumentation as part of the surgical procedure (i.e. fusion).
  • Diabetes.
  • Neuromuscular diseases.

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): NCT03442374


Contacts
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Contact: Samuel Ward, PT, PhD (858)534-4918 srward@ucsd.edu
Contact: Bahar Shahidi, PT, PhD (858)822-0439 bshahidi@ucsd.edu

Locations
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United States, California
UC San Diego Not yet recruiting
La Jolla, California, United States, 92093
Contact: Bahar Shahidi, PT, PhD    858-822-0439    bshahidi@ucsd.edu   
Contact: Samuel Ward, PT, PhD    (858)534-4918    srward@ucsd.edu   
Sponsors and Collaborators
University of California, San Diego
University of Zurich, Balgrist Hospital
Spine Institute of San Diego (Spine Zone)

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Responsible Party: Samuel R. Ward, Professor and Vice Chair of Research, University of California, San Diego
ClinicalTrials.gov Identifier: NCT03442374     History of Changes
Other Study ID Numbers: HD088437
First Posted: February 22, 2018    Key Record Dates
Last Update Posted: June 11, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by Samuel R. Ward, University of California, San Diego:
Multifidus
Muscle
Degeneration
Lumbar Spine
Disc

Additional relevant MeSH terms:
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Intervertebral Disc Degeneration
Back Pain
Low Back Pain
Pain
Neurologic Manifestations
Signs and Symptoms
Spinal Diseases
Bone Diseases
Musculoskeletal Diseases