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

NCT03880500 | Unknown DMC

• 1 other identifier: BalgristUH
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

Pain, Back

Outcome Measures

Primary Outcomes (3)

• Apparent Diffusion Coefficient Change

  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.

  Measured on day 1 during the study

• Capillary Perfusion Change

  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.

  Measured on day 1 during the study

• Diffusion Change

  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.

  Measured on day 1 during the study

Secondary Outcomes (3)

• Change in Apparent Diffusion Coefficient (Control)

  Measured approximately 9 hours after the first MRI, during the study

• Change in Capillary Perfusion (Control)

  Measured approximately 9 hours after the first MRI, during the study

• Diffusion change

  Measured approximately 9 hours after the first MRI, during the study

Other Outcomes (8)

• Pfirrmann-Grade

  Measured on day 1, during the study

• Weishaupt-Grade

  Measured on day 1, during the study

• Inflammatory Parameters (interleukins)

  Measured on day 1, during the study, and up to 12 months after

Study Arms (2)

Patient

SHAM COMPARATOR

25 Patients will receive a spinal manipulative therapy Intervention, the other 25 Patients receive a sham Intervention.

Other: Spinal Manipulative Therapy

Control

NO INTERVENTION

No intervention

Interventions

Spinal Manipulative Therapy OTHER

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.

Also known as: SMT, Spinal Manipulative Intervention, Thrust Manipulation, High-velocity, low-amplitude thrust

Patient

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients:
• 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).
• Source of LBP clinically at the L4/5 or L5/S1 segment.
• Duration of LBP is longer than 4 weeks
• Obtained informed consent.
• Controls:
• 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.
• Obtained informed consent.

You may not qualify if:

• Subjects are excluded from enrolment if they
• have undergone prior spinal surgery
• have undergone facet joint, epidural or periradicular injections in the last 6 months
• had a spinal manipulative therapy intervention in the past 2 weeks
• have spinal abnormalities (benign or malignant tumors, congenital abnormalities, isthmic spondylolisthesis)
• 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)
• have any contraindication to MRI (e.g. heart pacemaker, metallic foreign body or claustrophobia)
• have started a new prescription medication targeting blood circulation within the last 3 months
• are pregnant or nursing
• 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.

Sponsors & Collaborators

• Balgrist University Hospital: lead
• Verein Pro Chiropraktik: collaborator
• Balgrist Foundation: collaborator

Study Sites (1)

University Hospital Balgrist

Zurich, Canton of Zurich, 8008, Switzerland

RECRUITING

Related Publications (6)

• Beattie PF, Butts R, Donley JW, Liuzzo DM. The within-session change in low back pain intensity following spinal manipulative therapy is related to differences in diffusion of water in the intervertebral discs of the upper lumbar spine and L5-S1. J Orthop Sports Phys Ther. 2014 Jan;44(1):19-29. doi: 10.2519/jospt.2014.4967. Epub 2013 Nov 21.

  PMID: 24261925 BACKGROUND

• Le Bihan D. What can we see with IVIM MRI? Neuroimage. 2019 Feb 15;187:56-67. doi: 10.1016/j.neuroimage.2017.12.062. Epub 2017 Dec 22.

  PMID: 29277647 BACKGROUND

• Nguyen A, Ledoux JB, Omoumi P, Becce F, Forget J, Federau C. Application of intravoxel incoherent motion perfusion imaging to shoulder muscles after a lift-off test of varying duration. NMR Biomed. 2016 Jan;29(1):66-73. doi: 10.1002/nbm.3449.

  PMID: 26684052 BACKGROUND

• Wong AY, Parent EC, Dhillon SS, Prasad N, Kawchuk GN. Do participants with low back pain who respond to spinal manipulative therapy differ biomechanically from nonresponders, untreated controls or asymptomatic controls? Spine (Phila Pa 1976). 2015 Sep 1;40(17):1329-37. doi: 10.1097/BRS.0000000000000981.

  PMID: 26020851 BACKGROUND

• Klyne DM, Barbe MF, Hodges PW. Systemic inflammatory profiles and their relationships with demographic, behavioural and clinical features in acute low back pain. Brain Behav Immun. 2017 Feb;60:84-92. doi: 10.1016/j.bbi.2016.10.003. Epub 2016 Oct 6.

  PMID: 27720935 BACKGROUND

• Chou R, Huffman LH; American Pain Society; American College of Physicians. Nonpharmacologic therapies for acute and chronic low back pain: a review of the evidence for an American Pain Society/American College of Physicians clinical practice guideline. Ann Intern Med. 2007 Oct 2;147(7):492-504. doi: 10.7326/0003-4819-147-7-200710020-00007.

  PMID: 17909210 BACKGROUND

MeSH Terms

Conditions

Back Pain

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Petra Schweinhardt, PhD, MD

  Balgrist University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Malin B Muehlemann, Dr med.chiro

CONTACT

0041443865712; malin.muehlemann@balgrist.ch

Petra Schweinhardt, PhD, MD

CONTACT

0041443867381; petra.schweinhardt@balgrist.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Blinding of Investigator to type of Intervention Blinding of Outcome assesors during follow-up.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 20 Controls, 50 Patients

Study Record Dates

• First Submitted: December 6, 2018
• First Posted: March 19, 2019
• Study Start: March 6, 2019
• Primary Completion: June 1, 2024
• Study Completion: July 1, 2024
• Last Updated: August 15, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)