Brain MRI Research for Knee Osteoarthritis Pain

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how chronic pain from knee osteoarthritis (OA) affects the brain. Using advanced MRI techniques, researchers seek to identify specific brain changes linked to difficult-to-describe pain, potentially paving the way for new pain relief treatments. Participants will undergo MRI scans, including the Cold Pressor Gel Test (a method to assess pain response), and other assessments to gather this information. Individuals with knee OA and related pain, either localized to the knee or throughout the body, might be suitable for the study. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to innovative treatments for chronic pain.

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.

What prior data suggests that this MRI technique is safe for studying knee osteoarthritis pain?

Research has shown that the Cold Pressor Gel Test (CPGT) is generally safe for people. One study highlighted that the cold pressor test, using a gelled water product, includes safety measures, making it a safe choice for similar tests. Another study found that conducting the cold pressor test remotely is both feasible and acceptable for people with medical conditions, indicating participants manage it well without major issues.

These findings support the idea that the Cold Pressor Gel Test is safe and well-tolerated in clinical studies. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Cold Pressor Gel Test because it offers a unique way to understand pain mechanisms in knee osteoarthritis. Unlike standard pain treatments that primarily focus on managing symptoms, this approach uses MRI scans to observe how the brain processes pain signals before and after exposure to a cold stimulus. By collecting breath samples, researchers aim to uncover biomarkers related to pain response, potentially leading to more personalized and effective treatments in the future. This innovative method could pave the way for breakthroughs in pain management strategies, offering hope for those with knee osteoarthritis.

What evidence suggests that this trial's techniques could be effective for understanding knee osteoarthritis pain?

Research has shown that cold pressor tests can aid in understanding pain management in individuals with knee osteoarthritis (OA). One study found that people with knee OA experienced more pain and had lower cold tolerance, indicating a complex issue with pain processing. Another review found that cold treatments, such as cryotherapy, moderately reduced pain. These findings suggest that cold treatments might help manage knee OA pain by influencing how the brain processes pain. Although not a direct treatment, understanding these processes could lead to better therapies in the future. Participants in this trial will undergo the Cold Pressor Gel Test to further explore these mechanisms. ^{6 7 8 9 10}

Who Is on the Research Team?

Dinesh Kumbhare, MD, PhD

Principal Investigator

University Health Network, Toronto

Michael D Noseworthy, PhD, PEng

Principal Investigator

McMaster University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4944243/

Variability in conditioned pain modulation predicts response to ... Following diclofenac treatment, the knee OA cohort showed a roughly 30 % improvement in pain, regardless of the presence or absence of ...

2. dash.harvard.edu dash.harvard.edu/bitstreams/7312037d-eae6-6bd4-e053-0100007fdf3b/download

Variability in conditioned pain modulation predicts ... Tolerance for the cold pressor test was substantially lower among knee OA patients, and ratings of cold pain after-sensations were elevated (See Fig. 1).

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12168428/

Cryotherapy in Knee Osteoarthritis: A Systematic Review ... The meta‐analysis included all five studies in the pain intensity outcome, resulting in a standardized mean difference (SMD) of −0.57 (95% CI: [ ...

4. researchgate.net researchgate.net/figure/Pre-treatment-and-end-of-treatment-scores-on-clinical-outcome-measures-data-presented-as_fig3_305311872

Pre-treatment and end-of-treatment scores on clinical ... Consistent with prior results, the knee OA group showed significantly lower pain ... Pain‐Free Individuals Using a Tonic Heat Pain and Cold Pressor Test Paradigms.

5. journals.lww.com journals.lww.com/painrpts/_layouts/15/oaks.journals/downloadpdf.aspx?an=01938936-202308000-00001

a systematic review and The current systematic review and meta-analysis describe the predictive role of QST profiling for pain outcomes after total knee arthroplasty, NSAID, and ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27526332/

Preoperative Hypoalgesia After Cold Pressor Test and ... Hypoalgesia after cold pressor stimulation and aerobic exercise assessed preoperatively by cuff algometry was associated with pain relief 6 months after TKR.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27779778/

A safe alternative to the cold pressor test in fMRI Methods: The cold pressor test was modified to put safety precautions into the CPGT. The material used is cool gelled water with a thickening product, which ...

8. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0147526

Subjects with Knee Osteoarthritis Exhibit Widespread ... This study found widespread elevated pain thresholds in subjects with painful knee osteoarthritis, suggesting that altered nociceptive system processing may ...

9. frontiersin.org frontiersin.org/journals/pain-research/articles/10.3389/fpain.2024.1421709/full

Feasibility and acceptability of remote administration of the ... Conclusions: We demonstrated that a remote version of the cold pressor test is feasible and acceptable in a clinical population and provided a ...

10. sciencedirect.com sciencedirect.com/science/article/pii/S1526590014009080

Analysis of Meaningful Conditioned Pain Modulation Effect ... This study proposes a method for calculating meaningful CPM effect and reports the proportion and magnitude of effect elicited in a large sample.