- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03442374
Lumbar Spine Muscle Degeneration Inhibits Rehabilitation-Induced Muscle Recovery
Lumbar Spine Muscle Degeneration Inhibits Rehabilitation-Induced Muscle
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
AIM: To determine the effect of exercise on induction of muscle hypertrophic, fibrotic, inflammatory, and adipogenic pathways in patients with mild versus severe fatty infiltration of the multifidus muscle. Rationale. The objectives of this aim are to 1) measure molecular responses of muscle to a well-defined bout of pre-operative exercise, and 2) to determine if baseline morphological or exercise-induced molecular responses predict muscle structural recovery and functional gains up to 6 months post-operatively.
Design. This will be a longitudinal study of 40 patients with mild (< 20%) versus severe (> 50%) fatty infiltration. Non-exercise controls will also be important and the investigators intend to use a portion of biopsied tissue from other experiments as additional controls. Prior to surgery, patients will undergo clinical and MRI examinations. Additionally, patients will undergo an exercise bout 6 hours pre-operatively, and then immediately undergo a short MRI imaging protocol to measure exercise-induced perfusion changes (IVIM). Six hours after the exercise bout, the investigators will collect biopsies of the multifidus during surgery to characterize the hypertrophic, fibrotic, adipogenic, and inflammatory responses. For primary analyses, patient groups will be selected on the basis of severity of muscle fatty infiltration. Group ages and genders will be matched because the investigators know that baseline and exercise-induced gene expression varies with age. Surgical procedure and manipulation of the disc intraoperatively will be documented to account for the potential for disc and other surgery-specific effects on muscle structure. Six months post-operatively, repeated measures of muscle structure will be made via MRI. At 6, 12, and 24 weeks, strength (isokinetic dynamometer) and patient-specific function (questionnaire data) will be obtained as per standard protocol.
Methods:
Physical Examination: A physical therapist with spine injury experience will conduct the clinical exam. Age, gender and body mass index (BMI), duration of symptoms, anti-inflammatory drug use, active and passive range of motion, provocative neural tension tests (measuring joint range of motion [ROM]), strength and endurance as measured on an isokinetic dynamometer (MedX Holdings Inc.), neurovascular status, Oswestry Disability Index (81), Baecke Physical Activity Questionnaire (BPA), Fear Avoidance Beliefs Questionnaire (FABQ), and Pain Catastrophizing Scale (PCS) are important measures that capture both physical and psychosocial factors known to be related to LBP and will be collected at the clinical site. This screen will be used to confirm that discogenic symptoms are isolated to levels below L4, which allows us to use vastus lateralis as an internal control muscle biopsy.
Clinical MRI: Standard axial, sagittal oblique, and coronal oblique MR images of the spine will be collected on all patients who are scheduled for surgery. To identify disc injury severity (Pfirrmann grade), muscle fatty infiltration (Kjaer grade), and to confirm injury location, T1 and T2 non-fat suppressed or contrast-enhanced axial and sagittal MR images of the spine joint will be used.
Multimodal MRI: Imaging will be performed in a single session on a state-of-the-art 3T MRI system (GE MR750). The quantity and distribution of spine muscle volume, fat volume, and connective tissue volume will be performed from supine scans using high-resolution (1mm3) 3D FSPGR, IDEAL fat-water separation, and UTE pulse sequences, respectively using a 32-channel spine array coil. IVIM will be used to quantify regional muscle activation in response to an exercise bout.
Exercise protocol: Prior to surgery, patients will be subjected to a lumbar spine exercise protocol on a MedX Lumbar extension dynamometer with a pelvic restraint system allowing for isolation of lumbar spine muscles. 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.
Diet protocol: Importantly, the patients will remain NPO (no food or water) after the exercise bout but will have a standardized diet for 24 hours prior to the exercise bout and surgery, which mitigates the effects of diet on gene expression (137, 150-152). Evening meals will be standardized (1900h: 11 kcal/kg; 60% carbohydrate [CHO], 25% fat [FAT], 15% protein [PRO]; 2200h (3 kcal/kg; 95% CHO, 2% FAT, 3% PRO) because meal composition can acutely impact gene and protein expression.
Harvesting and storage of muscle biopsy: Muscle biopsies will be harvested within 6 hours of the exercise bout at their scheduled surgery time. Subjects will be excluded from the analysis if their biopsies are not harvested within 1 hour of the prescribed time point. Biopsies will be obtained with a standard biopsy clamp at the middle and deep margins of the multifidus muscle as noted in Aim #1 and immediately placed in RNAlater (Qiagen) for subsequent qPCR analysis or frozen in liquid nitrogen for protein abundance/phosphorylation measurements.
qPCR and western blotting: Gene expression and protein abundance will be measured by, qPCR and western blotting, respectively. Briefly, real-time PCR will be performed in a Bio-Rad CFX384 using customized plates (PrimePCR, Bio-Rad). Target gene expression will be calculated relative to values from 18S ribosomal subunit, as preliminary findings demonstrate it to be more stable than glyceraldehyde-3-phosphate dehydrogenase (GAPDH; data not presented). For genes in which we find a greater than 3-fold change in expression, western blotting will be used to assess protein abundance, as previously described.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
California
-
La Jolla, California, United States, 92093
- UC San Diego
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Exercise
A single bout of moderate intensity lumbar extensor muscle 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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Multifidus Muscle Fatty Infiltration
Time Frame: 6 months
|
(% fat at 6 months - % fat at baseline / % fat at baseline)
|
6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
6 Months
|
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
|
6 months
|
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
|
6 months
|
Change in Activated Muscle Volume (%)
Time Frame: After exercise (within 5 minutes)
|
(% muscle activation after exercise - % muscle activation at baseline / % muscle activation at baseline)
|
After exercise (within 5 minutes)
|
Change in Pain (VAS)
Time Frame: 6 months
|
Visual Analog Scale (0-100 mm scale), 6 months - baseline
|
6 months
|
Change in Strength
Time Frame: 6 months
|
MedEx dynamometer, Back Extensor Strength (Nm), 6 months - baseline
|
6 months
|
MYHC3 gene expression (delta CT/delta CT)
Time Frame: 6 hours after a single exercise bout
|
Embryonic myosin heavy chain gene expression
|
6 hours after a single exercise bout
|
MHY3 protein abundance (ug/mg)
Time Frame: 6 hours after a single exercise bout
|
Embryonic myosin heavy chain protein abundance
|
6 hours after a single exercise bout
|
MYOG gene expression (delta CT/delta CT)
Time Frame: 6 hours after a single exercise bout
|
Myogenin gene expression
|
6 hours after a single exercise bout
|
MYOG protein abundance (ug/mg)
Time Frame: 6 hours after a single exercise bout
|
Myogenin protein abundance
|
6 hours after a single exercise bout
|
PAX7 gene expression (delta CT/delta CT)
Time Frame: 6 hours after a single exercise bout
|
PAX7 gene expression
|
6 hours after a single exercise bout
|
PAX7 gene expression (ug/mg)
Time Frame: 6 hours after a single exercise bout
|
PAX7 protein abundance
|
6 hours after a single exercise bout
|
ANKRD2 gene expression (delta CT/delta CT)
Time Frame: 6 hours after a single exercise bout
|
ANKRD2 gene expression
|
6 hours after a single exercise bout
|
ANKRD2 protein abundance (ug/mg)
Time Frame: 6 hours after a single exercise bout
|
ANKRD2 protein abundance
|
6 hours after a single exercise bout
|
MTOR gene expression (delta CT/delta CT)
Time Frame: 6 hours after a single exercise bout
|
MTOR gene expression
|
6 hours after a single exercise bout
|
MTOR protein abundance (ug/mg)
Time Frame: 6 hours after a single exercise bout
|
MTOR protein abundance
|
6 hours after a single exercise bout
|
COL1A1 gene expression (delta CT/delta CT)
Time Frame: 6 hours after a single exercise bout
|
COL1A1 gene expression
|
6 hours after a single exercise bout
|
COL3A1 gene expression (delta CT/delta CT)
Time Frame: 6 hours after a single exercise bout
|
COL3A1 gene expression
|
6 hours after a single exercise bout
|
COL9A1 gene expression (delta CT/delta CT)
Time Frame: 6 hours after a single exercise bout
|
COL9A1 gene expression
|
6 hours after a single exercise bout
|
LOX gene expression (delta CT/delta CT)
Time Frame: 6 hours after a single exercise bout
|
LOX gene expression
|
6 hours after a single exercise bout
|
CTGF gene expression (delta CT/delta CT)
Time Frame: 6 hours after a single exercise bout
|
CTGF gene expression
|
6 hours after a single exercise bout
|
TGFB1 gene expression (delta CT/delta CT)
Time Frame: 6 hours after a single exercise bout
|
TGFB1 gene expression
|
6 hours after a single exercise bout
|
MMP1 gene expression (delta CT/delta CT)
Time Frame: 6 hours after a single exercise bout
|
MMP1 gene expression
|
6 hours after a single exercise bout
|
MMP3 gene expression (delta CT/delta CT)
Time Frame: 6 hours after a single exercise bout
|
MMP3 gene expression
|
6 hours after a single exercise bout
|
MMP9 gene expression (delta CT/delta CT)
Time Frame: 6 hours after a single exercise bout
|
MMP9 gene expression
|
6 hours after a single exercise bout
|
CEBPA gene expression (delta CT/delta CT)
Time Frame: 6 hours after a single exercise bout
|
CEBPA gene expression
|
6 hours after a single exercise bout
|
FABP4 gene expression (delta CT/delta CT)
Time Frame: 6 hours after a single exercise bout
|
FABP4 gene expression
|
6 hours after a single exercise bout
|
PPARG gene expression (delta CT/delta CT)
Time Frame: 6 hours after a single exercise bout
|
PPARG gene expression
|
6 hours after a single exercise bout
|
PPARD gene expression (delta CT/delta CT)
Time Frame: 6 hours after a single exercise bout
|
PPARD gene expression
|
6 hours after a single exercise bout
|
LEP gene expression (delta CT/delta CT)
Time Frame: 6 hours after a single exercise bout
|
LEP gene expression
|
6 hours after a single exercise bout
|
ADIPOQ gene expression (delta CT/delta CT)
Time Frame: 6 hours after a single exercise bout
|
ADIPOQ gene expression
|
6 hours after a single exercise bout
|
CASP1 gene expression (delta CT/delta CT)
Time Frame: 6 hours after a single exercise bout
|
CASP1 gene expression
|
6 hours after a single exercise bout
|
CASP3 gene expression (delta CT/delta CT)
Time Frame: 6 hours after a single exercise bout
|
CASP3 gene expression
|
6 hours after a single exercise bout
|
TNFa gene expression (delta CT/delta CT)
Time Frame: 6 hours after a single exercise bout
|
TNFa gene expression
|
6 hours after a single exercise bout
|
IL10 gene expression (delta CT/delta CT)
Time Frame: 6 hours after a single exercise bout
|
IL10 gene expression
|
6 hours after a single exercise bout
|
IL6 gene expression (delta CT/delta CT)
Time Frame: 6 hours after a single exercise bout
|
IL6 gene expression
|
6 hours after a single exercise bout
|
IL1B gene expression (delta CT/delta CT)
Time Frame: 6 hours after a single exercise bout
|
IL1B gene expression
|
6 hours after a single exercise bout
|
COL1A1 Protein abundance (ug/mg)
Time Frame: 6 hours after a single exercise bout
|
COL1A1 Protein abundance
|
6 hours after a single exercise bout
|
COL3A1 Protein abundance (ug/mg)
Time Frame: 6 hours after a single exercise bout
|
COL3A1 Protein abundance
|
6 hours after a single exercise bout
|
COL9A1 Protein abundance (ug/mg)
Time Frame: 6 hours after a single exercise bout
|
COL9A1 Protein abundance
|
6 hours after a single exercise bout
|
LOX Protein abundance (ug/mg)
Time Frame: 6 hours after a single exercise bout
|
LOX Protein abundance
|
6 hours after a single exercise bout
|
CTGF Protein abundance (ug/mg)
Time Frame: 6 hours after a single exercise bout
|
CTGF Protein abundance
|
6 hours after a single exercise bout
|
TGFB1 Protein abundance (ug/mg)
Time Frame: 6 hours after a single exercise bout
|
TGFB1 Protein abundance
|
6 hours after a single exercise bout
|
MMP1 Protein abundance (ug/mg)
Time Frame: 6 hours after a single exercise bout
|
MMP1 Protein abundance
|
6 hours after a single exercise bout
|
MMP3 Protein abundance (ug/mg)
Time Frame: 6 hours after a single exercise bout
|
MMP3 Protein abundance
|
6 hours after a single exercise bout
|
MMP9 Protein abundance (ug/mg)
Time Frame: 6 hours after a single exercise bout
|
MMP9 Protein abundance
|
6 hours after a single exercise bout
|
CEBPA Protein abundance (ug/mg)
Time Frame: 6 hours after a single exercise bout
|
CEBPA Protein abundance
|
6 hours after a single exercise bout
|
FABP4 Protein abundance (ug/mg)
Time Frame: 6 hours after a single exercise bout
|
FABP4 Protein abundance
|
6 hours after a single exercise bout
|
PPARG Protein abundance (ug/mg)
Time Frame: 6 hours after a single exercise bout
|
PPARG Protein abundance
|
6 hours after a single exercise bout
|
PPARD Protein abundance (ug/mg)
Time Frame: 6 hours after a single exercise bout
|
PPARD Protein abundance
|
6 hours after a single exercise bout
|
LEP Protein abundance (ug/mg)
Time Frame: 6 hours after a single exercise bout
|
LEP Protein abundance
|
6 hours after a single exercise bout
|
ADIPOQ Protein abundance (ug/mg)
Time Frame: 6 hours after a single exercise bout
|
ADIPOQ Protein abundance
|
6 hours after a single exercise bout
|
CASP1 Protein abundance (ug/mg)
Time Frame: 6 hours after a single exercise bout
|
CASP1 Protein abundance
|
6 hours after a single exercise bout
|
CASP3 Protein abundance (ug/mg)
Time Frame: 6 hours after a single exercise bout
|
CASP3 Protein abundance
|
6 hours after a single exercise bout
|
TNFa Protein abundance (ug/mg)
Time Frame: 6 hours after a single exercise bout
|
TNFa Protein abundance
|
6 hours after a single exercise bout
|
IL10 Protein abundance (ug/mg)
Time Frame: 6 hours after a single exercise bout
|
IL10 Protein abundance
|
6 hours after a single exercise bout
|
IL6 Protein abundance (ug/mg)
Time Frame: 6 hours after a single exercise bout
|
IL6 Protein abundance
|
6 hours after a single exercise bout
|
IL1B Protein abundance (ug/mg)
Time Frame: 6 hours after a single exercise bout
|
IL1B Protein abundance
|
6 hours after a single exercise bout
|
Change in Multifidus muscle volume (%)
Time Frame: baseline
|
Multifidus muscle volume (cc), (6 months - baseline/baseline)
|
baseline
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- HD088437
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Low Back Pain
-
Dow University of Health SciencesRecruitingLow Back Pain | Chronic Low-back Pain | Low Back Pain, Mechanical | Mechanical Low Back Pain | Pain, Chronic | Pain, Back | Lower Back Pain Chronic | CLBP - Chronic Low Back PainPakistan
-
Faculdade de Ciências Médicas da Santa Casa de...CompletedLow Back Pain, Mechanical | Low Back Pain, Postural | Lower Back Pain Chronic | Low Back Pain, Posterior CompartmentBrazil
-
University School of Physical Education in WroclawCompletedLow Back Pain | Low Back Pain, Mechanical | Low Back Pain, PosturalPoland
-
Texas Woman's UniversityTexas Physical Therapy AssociationCompletedLow Back Pain | Chronic Low Back Pain | Subacute Low Back PainUnited States
-
University of ParmaKing's College London; Helmholtz Zentrum München; GENOS; Ip Research Consulting... and other collaboratorsUnknownChronic Low Back Pain | Acute Low Back PainUnited States, Australia, Belgium, Croatia, Italy, United Kingdom
-
Karolinska InstitutetCompletedChronic Low Back Pain | Recurrent Low Back Pain | Persistent Low Back PainSweden
-
Ache Laboratorios Farmaceuticos S.A.Unknown
-
Palmer College of ChiropracticDepartment of Health and Human ServicesCompletedChronic Low Back Pain | Subacute Low Back PainUnited States
-
Universität Duisburg-EssenSiemens-BetriebskrankenkasseCompletedChronic Low Back Pain | Recurrent Low Back Pain
-
Apsen Farmaceutica S.A.CompletedLow Back Pain | Low Back Pain, Mechanical | Acute Low Back PainBrazil
Clinical Trials on Exercise
-
University of Kansas Medical CenterRecruiting
-
National Institute of Neurological Disorders and...TerminatedTraumatic Brain InjuryUnited States
-
University of Texas, El PasoRecruitingKnee Osteoarthritis | Knee Pain Chronic | Central Pain SyndromeUnited States
-
University of Alabama at BirminghamCompletedCystic FibrosisUnited States
-
University of LisbonFundação para a Ciência e a TecnologiaActive, not recruiting
-
University of Missouri-ColumbiaCompleted
-
University of AlcalaCompletedMyofascial Pain | Myofascial Pain Syndrome | Post Needling Soreness | Myofascial Trigger Point PainSpain
-
Bayero University Kano, NigeriaCompletedChronic Low Back PainNigeria
-
Toronto Rehabilitation InstituteCompletedAcute Myeloid LeukemiaCanada
-
Center for Health, Exercise and Sport Sciences,...CompletedSedentary LifestyleSerbia