Functional Brain MRI to Understand Pain Phenotypes in Knee Osteoarthritis

NCT07668674 | Not Yet Recruiting Phase 2

• 2 other identifiers: AOI 2025 MATHIEU2025-A02366-43
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

Brief Summary

Some people with knee osteoarthritis (gonarthrosis) experience pain differently. In some, the pain is described as "nociceptive" (directly related to the joint), while in others it has "neuropathic" characteristics (related to nerve function). The goal of this multicenter, cross-sectional and comparative study is to compare resting brain activity in a brain region called the anterior insula among female patients with painful knee osteoarthritis who experience nociceptive pain compared to those with neuropathic pain. Researchers will compare brain activity at rest between these two types of pain in women over 40 with painful knee osteoarthritis. A better understanding could help improve pain management in the future. Participants will be asked to :

• complete questionnaires during the inclusion visit and on the day of the scan,
• undergo a clinical examination and a blood test at the inclusion visit,
• undergo a functional MRI (fMRI), an imaging test that allows observation of brain activity at rest. Paticipants in the study does not involve any additional treatment. the fMRI scan is non-invasive and does not require any injections.

Conditions

Gonarthrosis; Neuropathic Pain, Nociceptive Pain

Keywords

Gonarthrosis; Neuropathic pain; Nociceptive Pain; Functional MRI; Anterior insula; Brain activity in the anterior insula at rest; INDIGO

Outcome Measures

Primary Outcomes (1)

• Resting-state anterior insula activity measured by functional MRI (BOLD signal amplitude)

  Comparison of resting-state anterior insula brain activity between patients with painful knee osteoarthritis with nociceptive pain and those with neuropathic-like pain, classified using the painDETECT questionnaire.

  At Visit 2 : within 30 days after inclusion, following Visit 1

Secondary Outcomes (3)

• Functional connectivity of the anterior insula with pain-related brain regions (resting-state MRI)

  At Visit 2 : within 30 days after inclusion

• Correlation between clinical pain scores ans anterior insula activity (resting-state fMRI)

  Clinical measures at Visit 1 and imaging measures at Visit 2 (within 30 days after inclusion)

• Correlation between clinical pain scores ans anterior insula functional connectivity (resting-state fMRI)

  Clinical measures at visit 1 ; imaging at visit 2 (within 30 days after inclusion)

Other Outcomes (1)

• Patient clusters identified using multimodal analysis including functional MRI and clinical data

  Data collected at Visit 1 and Visit 2 (within 30 days after inclusion)

Study Arms (2)

Nociceptive pain knee osteroarthritis

OTHER

Participants with painful knee osteoarthritis classified as having nociceptive pain based on PainDETECT questionnaire score ≤12.

Biological: blood sampling; Procedure: Resting-state functional MRI

Neuropathic-like pain knee osteoarthritis

OTHER

Participants with painful knee osteoarthritis classified as having neuropathic-like pain based on PainDETECT questionnaire score \>13.

Biological: blood sampling; Procedure: Resting-state functional MRI

Interventions

blood sampling BIOLOGICAL

Blood sampling will be performed at the inclusion visit. A biological assessment will include high sensitivity C reactive protein (hs-CRP) and metabolic markers (lipid profile, HbA1c, and fasting glucose). Additional blood samples (4 tubes) will be collected for biobank, including plasma and serum storage for the measurement of inflammatory markers.

Neuropathic-like pain knee osteoarthritis; Nociceptive pain knee osteroarthritis

Resting-state functional MRI PROCEDURE

Resting-state functional brain MRI will be performed at Visit 2 (within 30 days of the screening visit). Participants will undergo a brain MRI acquisition at rest to evaluate anterior insula activity and functional connectivity with pain-related brain regions.

Neuropathic-like pain knee osteoarthritis; Nociceptive pain knee osteroarthritis

Eligibility Criteria

• Age: 40 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women aged 40 or older (only women will be included to ensure consistency in the analyses, given the higher prevalence of osteoarthritis in women and the influence of sex/gender on the experience of pain)
• Diagnosis of femorotibial osteoarthritis of the knee according to the 1986 American College of Rheumatology criteria
• Presence of knee pain with an intensity of ≥ 4/10 on a numerical rating scale (NRS)
• Chronic knee pain, i.e., lasting at least 6 months with at least 15 days of pain in the past 30 days
• Completion of the PainDETECT questionnaire, which will allow the patient to be assigned to one of two groups prior to the enrollment visit (those with nociceptive pain \[score ≤ 12\] and those with neuropathic pain \[score \> 13\])
• Patients have read and understood the information letter
• Patients have signed the informed consent form
• Patients are enrolled in a social security program

You may not qualify if:

• Other joint diseases affecting the knees (gout, chondrocalcinosis, rheumatoid arthritis, spondyloarthritis, psoriatic arthritis)
• Conditions that, in the investigator's opinion, interfere with the assessment of osteoarthritic pain, such as conditions causing neuropathic pain in the lower extremities (e.g., peripheral neuropathy, chronic radiculopathy) or fibromyalgia
• Kellgren-Lawrence radiographic stage IV in one or both knees
• Patients with one or more knee prostheses
• Claustrophobia making MRI impossible
• Contraindication to MRI
• Pregnant or breastfeeding women
• Patients under guardianship, conservatorship, deprived of liberty, or under judicial protection
• Patients who have participated in an interventional clinical trial within the last 6 months that could impact the primary endpoint

Sponsors & Collaborators

• University Hospital, Clermont-Ferrand: lead

Study Sites (3)

CHU Clermont-Ferrand

Clermont-Ferrand, France

Location

APHP - Pitié-Salpêtrière

Paris, France

Location

APHP - Saint-Antoine

Paris, France

Location

MeSH Terms

Conditions

Osteoarthritis, Knee; Neuralgia; Nociceptive Pain

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Sylvain MATHIEU

  University Hospital, Clermont-Ferrand

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lise Laclautre

CONTACT

0473754963; promo_interne_drci@chu-clermontferrand.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2026
• First Posted: June 25, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: June 25, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)