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

NCT ID: NCT03880500

Last Updated: 2023-08-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-06
• Study Completion Date: 2024-07-31

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.

Detailed Description

Non-specific low back pain (LBP) is a very common condition in developed countries, with a point prevalence between 15% and 30% and a lifetime prevalence of about 70%. As a non-invasive treatment method, high-velocity, low-amplitude spinal manipulative therapy (SMT) is used in the conservative treatment of non-specific low back pain (LBP). Several studies suggest an association with favourable outcome. However, the overall effect size of clinical improvement following SMT remains modest. Most research on the effectiveness of SMT on back pain is conducted on patients suffering from "non-specific" LBP, the diagnosis of which is usually based upon the criterium that pain is not attributed to a recognizable pathology (e.g., infection, tumor, inflammatory diseases, fractures, disc herniations with nerve compression)8. In most of these studies, it is unclear whether patients' diagnoses were based upon more than history and clinical examination. The investigators argue that in the majority of cases, back pain labelled as non-specific might be more accurately labelled as non-specified and does have an attributable source and cause, whether one is able to recognize it or not. Therefore, if the diagnosis of non-specific LBP comprises heterogenic conditions, it is unlikely that patients will respond to one therapeutic modality equally.

Diffusion-weighted MR-imaging (DWI) is an application of magnetic resonance imaging that allows the measurement of water movement within and between tissues and is increasingly being used to study musculoskeletal physiology. Because DWI is sensitive even to small changes in fluid flow, it is potentially valuable in the study of the influence of therapeutic interventions such as manual therapy, exercise, and physical agents on musculoskeletal tissues. Studies using DWI have suggested that changes in diffusion within lumbar intervertebral discs occur in response to joint mobilization, prone press-ups, spinal traction and spinal manipulative therapy.

Intravoxel incoherent motion (IVIM) is a method proposed in 1988 by Le Bihan et al. which extracts microvascular blood flow information from diffusion-weighted imaging acquired at different b-values. It is used to generate separate images of diffusion and perfusion without requiring the injection of exogenous contrast agents. Originally developed in brain studies, it has been used in recent years to study perfusion in musculoskeletal tissue. There is a paucity of research addressing physiological events following a SMT intervention for patients with low back pain. A deeper understanding of local biomechanical and neurophysiological effects of SMT interventions might help refine its utilization and improve its effectiveness.

The purpose of this study is to quantify changes in diffusion and perfusion parameters within the intervertebral disc and paraspinal muscle tissue of a spinal segment receiving a spinal manipulative or sham intervention and to evaluate whether those changes differ in spinal segments with or without degenerative changes in 50 low-back-pain patients.

Additionally, it is of interest to determine the relationships between baseline parameters and changes in diffusion and perfusion as well as the degree of degenerative changes. Post-intervention changes in segmental spinal muscle perfusion will also be investigated. There will be a clinical follow-up immediately after the second MRI and at 1 week,4 and 12 weeks.

The repeatability and diurnal variation of IVIM imaging in quantifying perfusion in musculoskeletal tissues will be assessed by comparing perfusion parameters of 20 controls who will not receive any intervention. The investigators will perform a diffusion- and perfusion-weighted MRI at the beginning of the visit in the morning, which is repeated after approximately 20 minutes of rest (lying supine). Controls will present for an additional MRI approximately 10 hours later in the evening of the same day.

In participants consenting to venipuncture, approximately 8 ml of venous blood will be withdrawn using serum collection tubes, allowed to clot, and then centrifuged. The resulting serum supernatant is stored in aliquots at Balgrist Campus at -80°C. It will be analysed at the end of data collection for pro- and anti-inflammatory markers (e.g. C-reactive Protein, Interleukin 1-beta, Interleukin 6 and Tumor Necrosis Factor) in order to determine the relationship between inflammatory markers and degenerative changes, pain duration, and pain and disability outcomes.

Conditions

Pain, Back

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Patient

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

Group Type: SHAM_COMPARATOR

Spinal Manipulative Therapy

Intervention Type: 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.

Control

No intervention

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: OTHER

Other Intervention Names

SMT; Spinal Manipulative Intervention; Thrust Manipulation; High-velocity, low-amplitude thrust

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Verein Pro Chiropraktik

UNKNOWN

Sponsor Role: collaborator

Balgrist Foundation

UNKNOWN

Sponsor Role: collaborator

Balgrist University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Petra Schweinhardt, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

Balgrist University Hospital

Locations

University Hospital Balgrist

Zurich, Canton of Zurich, Switzerland

Site Status: RECRUITING

Countries

Switzerland

Central Contacts

Malin B Muehlemann, Dr med.chiro

Role: CONTACT

malin.muehlemann@balgrist.ch

0041443865712

Petra Schweinhardt, PhD, MD

Role: CONTACT

petra.schweinhardt@balgrist.ch

0041443867381

Facility Contacts

Petra Schweinhardt, MD PhD

Role: primary

petra.schweinhardt@balgrist.ch

0041443861111

References

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.

Reference Type: BACKGROUND

PMID: 24261925 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29277647 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26684052 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26020851 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27720935 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17909210 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

BalgristUH

Identifier Type: -

Identifier Source: org_study_id