Clinical trial NCT05097729: rTMS for Relieving Chronic OA Pain
Official title: Transcranial Magnetic Stimulation to Enhance Cortical Hippocampal Functional Connectivity as a Novel Means for Relieving Chronic OA Pain
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Chronic Pain
Osteo Arthritis Knee
Lead sponsor: Northwestern University
Sponsor class: OTHER
First posted: 2021-10-28
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: All participants will receive all the 3 modalities of stimulation in a randomized order. Each round is composed by 5 daily sessions of stimulation. Participants will have a second MRI only after Modality one (hippocampal).
Primary purpose: TREATMENT

Brief summary: In this study the investigators aim to examine the effects of Transcranial Magnetic Stimulation (TMS) on hippocampal network connectivity and pain levels in individuals with pain due to knee osteoarthritis.

Detailed description: Osteoarthritis (OA) pain is one of the most prevalent causes of chronic pain worldwide. Symptoms can last from months to a lifetime, severely impacting patients' quality of life. New strategies - including non-invasive brain stimulation techniques - have shown promise for sustained pain relief, yet evidence on their reliability and efficacy is limited. Apkarian et. al have previously shown that the dorsal hippocampus plays a central role in pain analgesia; thus, the study aim is to test whether non-invasively enhancing dorsal hippocampus activity is a useful new strategy for pain relief in knee OA patients. This study will recruit 35 patients with chronic OA pain for \> 6 months. Each participant will receive 3 rounds of different treatment modalities in a cross-over manner. Each treatment modality will consist of 5 daily consecutive rTMS sessions followed by a 2-weeks wash-out period. Questionnaires will be completed prior to and following each intervention, and after each treatment round. Participants will be trained to use a pain electronic application (smartphone-based tool to rate pain intensity and mood on NRS scales, as well as indicate rescue medication use, developed in our lab). They will be asked to use this application for 7-10 days prior to the first round of intervention and during the study duration.

Eligibility criteria: Inclusion Criteria:

* ≥ 6 months of knee pain on a daily basis;
* male or female with no racial or ethnic restrictions;
* 18 to 75 years old;
* average knee pain intensity \> 4/10 at study entry;
* must be able to read, understand, and sign consent form;
* generally healthy.
* able to use the PainApp

Exclusion Criteria:

* rheumatoid arthritis, ankylosing spondylitis, acute vertebral fractures,
* Chronic neurologic conditions, e.g., Parkinson's
* other severe medical diseases;
* pregnancy;
* positive urinary screen for any recreational drugs,
* opioids use;
* use of anticoagulants (low dose ASA allowed);
* history of gastric ulcer; renal insufficiency or congestive heart failure,
* contraindication to MRI,
* contraindication to TMS; including history of seizure/epilepsy\*
* Any medical condition that in the investigator's judgment may prevent the individual from completing the study or put the individual at undue risk;
* In the judgment of the investigator, unable or unwilling to follow protocol and instructions.
* Diagnosis of major depression.

Primary outcomes:
measure: Pain ratings (Numeric Rating Scale)
timeFrame: Pain ratings immediately after each rTMS modality and effects after the end of stimulation round (1 week).
Secondary outcomes:
measure: Pain trajectories
timeFrame: 1 to 12 weeks (end of the study)
measure: Brain biomarkers and psychological indicators of rTMS effects and pain relief
timeFrame: 1 to 12 weeks (end of the study)
measure: Adverse events
timeFrame: 1 to 12 weeks (end of the study)
measure: Global impression of change
timeFrame: 1 to 12 weeks - after each rTMS round.
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
Study officials:
References: