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Spinal Segment MRI Perfusion and Diffusion Response to Spinal Manipulation in Low Back Pain Patients

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ClinicalTrials.gov Identifier: NCT03880500
Recruitment Status : Not yet recruiting
First Posted : March 19, 2019
Last Update Posted : March 19, 2019
Sponsor:
Collaborators:
Verein Pro Chiropraktik
Balgrist Foundation
Information provided by (Responsible Party):
Balgrist University Hospital

Brief Summary:

The main objective is to quantify changes in diffusion and perfusion in the intervertebral disc and adjacent spinal muscle tissue of a spinal segment receiving a spinal manipulative or control intervention using diffusion-weighted magnetic resonance Imaging (MRI) (DWI, used for quantifying diffusion) and intravoxel incoherent motion MRI (IVIM, used for quantifying perfusion).

Additional objectives are to test if clinical parameters such as pain and disability, radiological parameters, or pain-related inflammatory parameters in venous blood have predictive value in relation to these perfusion and diffusion effects, and if these effects correlate to clinical outcome.

An additional objective is to test the repeatability of IVIM-MRI in assessing perfusion changes in musculoskeletal tissue, and, as a positive control, assessing diurnal changes in perfusion and diffusion parameters in spinal tissue of healthy controls.


Condition or disease Intervention/treatment Phase
Pain, Back Other: Spinal Manipulative Therapy Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 20 Controls, 50 Patients
Masking: Double (Investigator, Outcomes Assessor)
Masking Description: Blinding of Investigator to type of Intervention Blinding of Outcome assesors during follow-up.
Primary Purpose: Treatment
Official Title: MRI-quantified Changes in Perfusion and Diffusion in Spinal Segments After High-Velocity, Low-Amplitude Spinal Manipulation: A Randomized Controlled Trial
Estimated Study Start Date : March 2019
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : December 2020

Arm Intervention/treatment
Sham Comparator: Patient
25 Patients will receive a spinal manipulative therapy Intervention, the other 25 Patients receive a sham Intervention.
Other: Spinal Manipulative Therapy
The patient lies in sidelying position, with the hip of the upper leg flexed to 90° and the foot of the flexed leg hooked behind the popliteal space of the downside leg. The chiropractor faces the subject at a 45°-angle, fixates the flexed knee with his own knee/thigh. The fingers of the cephalic hand reach under the patient's upper arm to contact the upside lateral surface of the superior spinous process. The fingers of the caudal hand hook down-side aspect of the spinous process, the forearm contacts the patient's buttock and thigh. The cephalic hand thrusts lateromedially and caudocranially, from upside toward downside (push). The caudal hand thrusts lateromedially in the opposing direction, from downside toward upside (pull). SMT is repeated after the patient turns to left side lying.
Other Names:
  • SMT
  • Spinal Manipulative Intervention
  • Thrust Manipulation
  • High-velocity, low-amplitude thrust

No Intervention: Control
No intervention



Primary Outcome Measures :
  1. Apparent Diffusion Coefficient Change [ Time Frame: Measured on day 1 during the study ]
    Computed on diffusion-weighted MRI, refers to the mean diffusion in a voxel (on MRI). Apparent diffusion coefficient (ADC) is measured in the intervertebral disc and adjacent spinal muscle tissue in patients before and after an SMT- or control intervention and in controls before and after 20 minutes of lying supine. The computed difference is the Apparent Diffusion Coefficient Change.

  2. Capillary Perfusion Change [ Time Frame: Measured on day 1 during the study ]
    Also called pseudodiffusion or D*. Measured on IVIM-MRI in square millimeters per second. Perfusion in capillaries in spinal muscle tissue is measured in patients before and after an SMT- or control intervention and in controls before and after 20 minutes of lying supine. The computed difference equals the Capillary Perfusion Change.

  3. Diffusion Change [ Time Frame: Measured on day 1 during the study ]
    Measured on diffusion-weighted MRI in square millimeters per second. Diffusion (D) in intra- and extracellular compartments in the intervertebral disc and adjacent spinal muscle tissue is measured in patients before and after an SMT- or control intervention and in controls before and after 20 minutes of lying supine. The computed difference is the Diffusion Change.


Secondary Outcome Measures :
  1. Change in Apparent Diffusion Coefficient (Control) [ Time Frame: Measured approximately 9 hours after the first MRI, during the study ]
    Measured on MRI. Secondary outcomes are the diurnal changes of the apparent diffusion coefficient in musculoskeletal tissue in controls approximately 9 hours after the first MRI.

  2. Change in Capillary Perfusion (Control) [ Time Frame: Measured approximately 9 hours after the first MRI, during the study ]
    Secondary outcomes are the diurnal changes of capillary perfusion in musculoskeletal tissue in controls approximately 9 hours after the first MRI.

  3. Diffusion change [ Time Frame: Measured approximately 9 hours after the first MRI, during the study ]
    Secondary outcomes are the diurnal changes of diffusion in the intervertebral disc and adjacent spinal muscle tissue in controls approximately 9 hours after the first MRI.


Other Outcome Measures:
  1. Pfirrmann-Grade [ Time Frame: Measured on day 1, during the study ]

    The severity of degenerative changes classified according to the Pfirrmann-grade on MRI.

    Grade I: disc is homogeneous with bright hyperintense white signal intensity and normal disc height.

    Grade II: disc is inhomogeneous, but keeping the hyperintense white signal. Nucleus and annulus are clearly differentiated, and a gray horizontal band could be present. Disc height is normal.

    Grade III: disc is inhomogeneous with an intermittent gray signal intensity. Distinction between nucleus and annulus is unclear. Disc height is normal or slightly decreased Grade IV: Disc is inhomogeneous with a hypointense dark gray signal intensity. There is no more distinction between the nucleus and annulus. Disc height is slightly or moderately decreased.

    Grade V: Disc is inhomogeneous with a hypointense black signal intensity. There is no more difference between the nucleus and annulus. The disc space is collapsed.


  2. Weishaupt-Grade [ Time Frame: Measured on day 1, during the study ]

    The severity of degenerative changes classified according to the Weishaupt-Classification on MRI.

    0 Normal facet joint space (2±4 mm width)

    1. Narrowing of the facet joint space (< 2 mm) and/or small osteophytes and/or mild hypertrophy of the articular process
    2. Narrowing of the facet joint space and/or moderate osteophytes and/or moderate hypertrophy of the articular process and/or mild subarticular bone erosions
    3. Narrowing of the facet joint space and/or large osteophytes and/or severe hypertrophy of the articular process and/or severe subarticular bone erosions and/or subchondral cysts

  3. Inflammatory Parameters (interleukins) [ Time Frame: Measured on day 1, during the study, and up to 12 months after ]
    The concentration of pro- and anti-inflammatory markers (Interleukin 1-beta, 4, 6, and 8) in the obtained blood samples.

  4. Inflammatory Parameters (CRP) [ Time Frame: Measured on day 1, during the study ]
    The concentration of CRP in the obtained blood samples.

  5. Inflammatory Parameters (TNF-alpha) [ Time Frame: Measured on day 1, during the study ]
    The concentration of TNF-Alpha in the obtained blood samples.

  6. Disability Change [ Time Frame: Disability change is assessed at 1 week, 1 month and 3 months follow-up ]
    Change in Oswestry disability Index. The questionnaire contains ten topics: intensity of pain, lifting, ability to care for oneself, ability to walk, ability to sit, sexual function, ability to stand, social life, sleep quality, and ability to travel. Each category consists of 6 statements describing different scenarios in the patient's life relating to the category. The patient checks the statement which most precisely resembles their situation. Each question is scored on a scale of 0-5 with the first statement being zero and indicating the least disability and the last statement is scored 5 indicating the most disability. The scores for all questions answered are added, then multiplied by two to obtain the index (range 0 to 100).

  7. Pain Change: NRS [ Time Frame: Pain change is assessed at 1 week, 1 month and 3 months follow-up ]
    Change in pain on the numerical Rating scale NRS (11-point Scale ranging from 0 (no pain) to 10 (most pain).

  8. Treatment-related adverse events [ Time Frame: Treatment-related adverse events are assessed at all time points during the study, starting from the time of inclusion to completion of 3 months follow up ]
    Number of participants with treatment-related adverse events as defined in the study Protocol Chapter 8.2.4.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria:

Patients:

  1. Persons over 18 years and under 75 years of age with low back pain of any duration clinically not attributable to "red flags" (infection, trauma, fractures, inflammatory illnesses).
  2. Source of LBP clinically at the L4/5 or L5/S1 segment.
  3. Duration of LBP is longer than 4 weeks
  4. Obtained informed consent.

Controls:

  1. Persons over 18 years and under 75 years of age who have not suffered from low back pain in the last year and have never experienced low back pain for longer than 7 consecutive days.
  2. Obtained informed consent.

Exclusion criteria:

Subjects are excluded from enrolment if they

  1. have undergone prior spinal surgery
  2. have undergone facet joint, epidural or periradicular injections in the last 6 months
  3. had a spinal manipulative therapy intervention in the past 2 weeks
  4. have spinal abnormalities (benign or malignant tumors, congenital abnormalities, isthmic spondylolisthesis)
  5. have any contraindication to spinal manipulative interventions or are deemed unable to tolerate SMT to both body sides (e.g. pain attributable to above mentioned red flags, inability to perform side-lying without pain, radiculopathy with motor deficits <M4-, severe spinal canal stenosis)
  6. have any contraindication to MRI (e.g. heart pacemaker, metallic foreign body or claustrophobia)
  7. have started a new prescription medication targeting blood circulation within the last 3 months
  8. are pregnant or nursing
  9. Subjects are excluded from venipuncture if they are known to be HIV-positive or have Hepatitis A, B, or C or have another systemic infection (excludes subjects from venipuncture). No study specific testing for HIV or Hepatitis A, B or C is performed.

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): NCT03880500


Contacts
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Contact: Malin B Muehlemann, Dr med.chiro 0041443865712 malin.muehlemann@balgrist.ch
Contact: Petra Schweinhardt, PhD, MD 0041443867381 petra.schweinhardt@balgrist.ch

Sponsors and Collaborators
Balgrist University Hospital
Verein Pro Chiropraktik
Balgrist Foundation
Investigators
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Principal Investigator: Petra Schweinhardt, PhD, MD Balgrist University Hospital
  Study Documents (Full-Text)

Documents provided by Balgrist University Hospital:

Publications:

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Responsible Party: Balgrist University Hospital
ClinicalTrials.gov Identifier: NCT03880500     History of Changes
Other Study ID Numbers: BalgristUH
First Posted: March 19, 2019    Key Record Dates
Last Update Posted: March 19, 2019
Last Verified: March 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

Additional relevant MeSH terms:
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Back Pain
Pain
Neurologic Manifestations
Signs and Symptoms