Brain MRI Research for Knee Osteoarthritis Pain

Recruiting at 1 trial location

Overseen By Ethan Danielli, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Toronto Rehabilitation Institute

Must not be taking: Psychotropic medications

Disqualifiers: Liver disease, Kidney disease, Fibromyalgia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

66 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are using psychotropic medications, you may not be eligible to participate.

Is the Cold Pressor Gel Test safe for humans?

The Cold Pressor Gel Test is described as a safe method for delivering a pain stimulus in brain imaging studies. ^{1 2 3 4 5}

How does the treatment in the Brain MRI Research for Knee Osteoarthritis Pain differ from other treatments?

This treatment is unique because it focuses on understanding how knee osteoarthritis pain affects the brain using MRI scans, rather than directly targeting the knee joint itself. It explores the brain's response to pain and potential neuroplastic changes, which is different from traditional treatments that primarily address joint inflammation and pain relief. ^{3 4 6 7 8}

What is the purpose of this trial?

It has been estimated that 300 million people worldwide have osteoarthritis (OA), and this has increased by 97% over the past 25 years. OA is degenerative joint disease that has joint cartilage break down and causes the surrounding bone to change and rub. The pain and loss of mobility experienced by people with knee OA can seriously reduce quality of life, while pain management causes significant healthcare spending. Unfortunately, the pain associated with OA is complex and difficult to treat other than to have a total knee replacement surgery to replace the damaged bone and surrounding tissues with artificial ones. Our research study plans to use advanced magnetic resonance imaging techniques and novel analysis methods to determine if specific parts of the brain are responsible for difficult to describe and diagnose aspects of chronic pain. This study will help us better understand the effects of chronic pain in the brain and the results will help guide future research into new therapeutic options that would focus on relieving the brain dysfunction caused by chronic pain.

Research Team

Dinesh Kumbhare, MD, PhD

Principal Investigator

University Health Network, Toronto

Michael D Noseworthy, PhD, PEng

Principal Investigator

McMaster University

Eligibility Criteria

This trial is for English-speaking adults with knee osteoarthritis (OA) confirmed by a rheumatologist, who have had chronic knee pain for over 3 months. Participants must not be on psychotropic meds, pregnant, or have liver/kidney disease. They can't have metal implants, claustrophobia, substance abuse issues, fibromyalgia, inflammatory disorders like rheumatoid arthritis or depression.

Inclusion Criteria

I have had knee pain for more than 3 months due to arthritis.

I have chronic knee pain and pain in more than 3 areas of my body.

I have been diagnosed with knee osteoarthritis by a rheumatologist.

Exclusion Criteria

I have had a total knee replacement.

Pregnant or chance of being pregnant

I have never had chronic or knee pain from osteoporosis or osteoarthritis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

30 minutes

1 visit (phone call)

Data Collection

Participants undergo MRI scans and complete pain assessment questionnaires

2 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after data collection

4 weeks

Treatment Details

Interventions

• Cold Pressor Gel Test

Trial Overview The study uses advanced brain MRI to explore how chronic knee OA pain affects the brain. It aims to identify specific brain areas linked to complex and hard-to-treat aspects of chronic pain in order to guide future treatments targeting these dysfunctions.

Participant Groups

Group I: OA-Knee+Body Experimental Treatment 1 Intervention

Individuals with knee OA with localized knee pain and widespread bodily pain. All participants will complete the same study protocol with pre- post-perturbation MRI scans and pain assessment questionnaires, as well as breath samples collected at multiple time points during the study visit.

Group II: OA-Knee Experimental Treatment 1 Intervention

Individuals with knee OA with localized knee pain. All participants will complete the same study protocol with pre- post-perturbation MRI scans and pain assessment questionnaires, as well as breath samples collected at multiple time points during the study visit.

Group III: OA-PF Active Control 1 Intervention

Individuals with knee OA without knee or bodily pain. All participants will complete the same study protocol with pre- post-perturbation MRI scans and pain assessment questionnaires, as well as breath samples collected at multiple time points during the study visit.

Who Is Running the Clinical Trial?

Toronto Rehabilitation Institute

Lead Sponsor

Trials

55

Recruited

6,000+

McMaster University

Collaborator

Trials

936

Recruited

2,630,000+

Findings from Research

The cold pressor gel test (CPGT) is a new, safe, and reproducible method for inducing pain in experimental settings, specifically designed for use with functional MRI (fMRI) studies.

In a study involving 13 women with chronic pelvic pain, the CPGT maintained a stable low temperature during the pain stimulus, leading to significant brain activation related to chronic pain processing, demonstrating its effectiveness as a pain delivery tool.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cold pressor gel test: A safe alternative to the cold pressor test in fMRI. Lapotka, M., Ruz, M., Salamanca Ballesteros, A., et al.[2018]

This study used a 7 Tesla fMRI scanner to detect significant changes in brain activity in response to a cold pressor test (CPT) in 11 healthy participants, highlighting the potential of advanced imaging techniques to study brainstem responses.

The results showed increased BOLD signal intensity in specific brain regions, including the dorsal medulla, indicating that BOLD fMRI can effectively measure brainstem activity related to neurogenic hypertension during cold stress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brainstem Correlates of a Cold Pressor Test Measured by Ultra-High Field fMRI. Hendriks-Balk, MC., Megdiche, F., Pezzi, L., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Cold pressor gel test: A safe alternative to the cold pressor test in fMRI. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Demonstration and validation of a new pressure-based MRI-safe pain tolerance device. [2019]

3. Canada pubmed.ncbi.nlm.nih.gov

Naproxen effects on brain response to painful pressure stimulation in patients with knee osteoarthritis: a double-blind, randomized, placebo-controlled, single-dose study. [2014]

4. Spain pubmed.ncbi.nlm.nih.gov

Effects of chondroitin sulfate on brain response to painful stimulation in knee osteoarthritis patients. A randomized, double-blind, placebo-controlled functional magnetic resonance imaging study. [2018]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Brainstem Correlates of a Cold Pressor Test Measured by Ultra-High Field fMRI. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Structural and functional brain changes in people with knee osteoarthritis: a scoping review. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Structural and Functional Abnormalities in Knee Osteoarthritis Pain Revealed With Multimodal Magnetic Resonance Imaging. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Brain gray matter alterations in Chinese patients with chronic knee osteoarthritis pain based on voxel-based morphometry. [2018]