The Role of Disc Nutrition in the Etiology and Clinical Treatment of Disc Degeneration

The purpose of this research study is to examine the effects of physical therapy on the spinal discs. Back pain is the number one cause of disability in the US, and the spine is the most common location of chronic pain in Veterans. Physical therapy is often very effective at improving patients' back pain, but it does not work for everyone, and it is not understood how physical therapy alters the tissues within the spine. With this research the investigators hope to learn if the investigative team can measure changes to the spinal discs on MRI scans that might predict if a patient's back pain will improve with physical therapy or not.

Study Overview

• Status: Not yet recruiting
• Conditions: Back Pain; Intervertebral Disc Degeneration
• Intervention / Treatment: Procedure: Physical Therapy

Detailed Description

Low back pain, which is frequently associated with intervertebral disc degeneration, is the most common cause of adult disability in the United States. Among active service members, the incidence of disc degeneration more than doubled from 2001 to 2010, with over 68,000 days of lost duty time attributed to disc degeneration.2 The most common location of chronic pain in Veterans is the spine. The incidence of back pain in the general public has remained relatively stable over the past decade, however, there has been more than a 50% increase in the number of Veterans diagnosed with back pain. The intervertebral discs are the largest avascular structures in the body, and therefore cells within the disc rely on transport from the small vessels in the adjacent vertebral endplate to receive nutrients and expel waste products. Despite the immense social and economic burden of back pain, the etiology of disc degeneration remains poorly understood. Because of the avascular nature of the disc, it has been speculated that poor disc nutrition characterized by reduced trans-endplate transport into the disc could contribute to the initiation and progression of degeneration. If a reduction in trans-endplate transport of nutrients and waste products is a primary contributor to the initiation and progression of the degenerative cascade, then enhancing disc nutrition may have a therapeutic effect. Physical therapy and exercise can be very effective in managing back pain for certain patients, yet it is not fully understood why certain patients respond to physical therapy and others do not, and what effects such interventions have on disc nutrition and disc health. The goal of this study is to undertake a pilot study to determine the feasibility and preliminary outcomes of utilizing quantitative MRI in human patients to quantify changes in disc health and trans-endplate transport over the course of physical therapy.

To do so, patients with low back pain and concomitant disc degeneration, who have not had prior spinal surgery, will be recruited. Recruited patients will undergo MRI T2-mapping and post-contrast enhanced T1-mapping of their lumbar spines at 1.5T to measure disc health and nutrition, respectively. Patients will then begin a 6 week physical therapy treatment regimen, after which the same MRI scans will be performed again on each patient. Pain and disability level of patients will be assessed via the visual analog scale (VAS) and Oswestry Disability Index (ODI) questionnaires, both pre- and post-treatment. Lumbar active range of motion will also be quantified at the initial and final in-office physical therapy session. Inclinometers will be placed at the thoracolumbar junction and sacrum, and the patient asked to bend forward and backward. Lumbar flexion will be quantified as the difference in motion between the two inclinometers.

Significant differences T1 and T2 values in the disc, as well as VAS and ODI scores and lumbar range of motion, before and after physical therapy will be assessed via a paired t-test, with significance defined as p<0.05. Univariate linear correlations between the changes in T1 or T2 values and changes in VAS, ODI scores and lumbar range of motion will be performed to determine if altered disc health or nutrition with physical therapy is significantly correlated with improvements in pain and disability.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sarah E Gullbrand, PhD; Phone Number: (215) 823-5800; Email: sgullb@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-4551
      • Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
      • Contact: Sarah E Gullbrand, PhD; Phone Number: 215-823-5800; Email: sgullb@pennmedicine.upenn.edu
      • Principal Investigator: Sarah E. Gullbrand, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Current activity limiting low back pain
• With symptoms of any duration
• With or without symptoms extending distal to the buttocks
• Medically stable
• Candidate for physical therapy

Exclusion Criteria:

• Documented history of prior spinal surgery

• Contraindications to MRI including:

  • claustrophobia
  • pregnancy

  • implanted electronic devices

    • pacemakers, cochlear implant, insulin pumps, etc

  • metallic foreign bodies

    • i.e. shrapnel

  • documented history of contraindications to gadodiamide (Omniscan) administration:

    • chronic severe kidney disease
    • acute kidney injury
    • impaired elimination of gadolinium based contrast agents
    • pre-existing renal insufficiency
    • a prior hypersensitivity reaction to MRI contrast

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Physical therapy; Subjects will be prescribed a 6-week physical therapy regimen consisting of one 45 minute in office visit per week, and home exercises performed daily. The in-office visits with a physical therapy provider will consist of the application of manual therapy, particularly high-velocity, low amplitude thrust mobilization in the anterior/posterior direction of the lumbar spine. In office visits will also include supervised repeated motion of the lumbar spine into extension (McKenzie therapy, 3 sets of 10 repetitions, in prone and standing positions) Patients will be instructed to complete these repeated extension exercises at home daily for the 6 week period.

Procedure: Physical Therapy; Subjects will be prescribed a 6-week physical therapy regimen consisting of one 45 minute in office visit per week, and home exercises performed daily. The in-office visits with a physical therapy provider will consist of the application of manual therapy, particularly high-velocity, low amplitude thrust mobilization in the anterior/posterior direction of the lumbar spine. In office visits will also include supervised repeated motion of the lumbar spine into extension (McKenzie therapy, 3 sets of 10 repetitions, in prone and standing positions) Patients will be instructed to complete these repeated extension exercises at home daily for the 6 week period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Disc T2 relaxation time	Subjects will undergo MRI scanning to obtain T2-maps of the lumbar spine before and after 6 weeks of physical therapy. T2 relaxation times of the disc tissues are calculated from the images.	0 to 6 weeks
Change in Visual Analog Scale (VAS) score	Subjects will complete a visual analog scale (VAS) for their back pain before and after 6 weeks of physical therapy. This is a scale from 0 (no pain) to 15 (the worst imaginable pain).	0 to 6 weeks
Change in Lumbar Range of Motion	Lumbar range of motion will be measured using inclinometers placed on the subject's upper and lower back, at both the index and final in-office physical therapy visit.	0 to 6 weeks
Change in Disc T1 relaxation time	Subjects will undergo MRI scanning to obtain post-contrast enhanced T1 maps of the lumbar spine before and after 6 weeks of physical therapy. To obtain the T1 maps, an intravenous catheter will be placed, and 0.1 mmols/kg of Omniscan will be administered. T1 MRIs will be acquired prior to and 2 hours following Omniscan administration. T1 relaxation times of the disc tissues are calculated from the images.	0 to 6 weeks
Change in Oswestry Disability Index (ODI) score	Subjects will complete the ODI questionnaire before and after 6 weeks of physical therapy. This is a scale from 0 (no disability) to 50 (bed bound).	0 to 6 weeks

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Sarah E. Gullbrand, PhD, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2024
• Primary Completion (Estimated): February 2, 2026
• Study Completion (Estimated): February 2, 2026

Study Registration Dates

• First Submitted: October 18, 2019
• First Submitted That Met QC Criteria: October 18, 2019
• First Posted (Actual): October 22, 2019

Study Record Updates

• Last Update Posted (Actual): May 8, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: imaging; intervertebral disc; physical therapy; spine
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Spinal Diseases; Bone Diseases; Intervertebral Disc Degeneration
• Other Study ID Numbers: B3118-W

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No