Chronic PainNCT05097729
rTMS for Relieving Chronic OA Pain
A study testing Transcranial Magnetic Stimulation in people with Chronic Pain and Osteo Arthritis Knee, run by Northwestern University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Chronic Pain, Osteo Arthritis Knee
- What is being tested?
- Transcranial Magnetic Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Nov 2021to 1 Jan 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥ 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
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Transcranial Magnetic Stimulation to Enhance Cortical Hippocampal Functional Connectivity as a Novel Means for Relieving Chronic OA Pain
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.
Read the 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.
- Conditions
- Chronic Pain, Osteo Arthritis Knee
- Being tested
- Transcranial Magnetic Stimulation
- Medical subject headings
- Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Magnetic StimulationDevice
Also called TMS
The brain stimulation can be delivery using different devices; in this project a MagPro X100 stimulator connected to a MagPro Cool-B65 liquid-cooled butterfly coil (MagVenture A/S, Farum, Denmark) will be used. Resting motor threshold (M1-rTMS) will be determined during the visit 1 or visit 2 and used along all visits. The rTMS pulse sequences and intensities used are all within the published safety guidelines
| Study group | Role | What they receive |
|---|---|---|
| Stimulation Modality 1 | Experimental | Repetitive TMS will be applied at 100% resting motor threshold intensity to a region of interest located in the parietal cortex, that will be determined based on its connectivity with the hippocampus. Receives: Device: Transcranial Magnetic Stimulation |
| Stimulation Modality 2 | Sham comparator | Parameters will be identical to the modality 1, except that the coil will be flipped over. Receives: Device: Transcranial Magnetic Stimulation |
| Stimulation Modality 3 | Active comparator | The stimulation will be delivered over the motor cortex contralateral to the predominant painful region, i.e., right motor cortex stimulation if left knee pain. The stimulation intensity will be set at 80% of the resting motor threshold. Receives: Device: Transcranial Magnetic Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain ratings (Numeric Rating Scale)
The primary efficacy outcomes are the effects of the rTMS modalities on pain app ratings.
Measured: Pain ratings immediately after each rTMS modality and effects after the end of stimulation round (1 week).
Secondary outcomes (4)
Pain trajectories
Individual pain trajectories will be analyzed to assess rTMS effects with greater temporal granularity.
Measured: 1 to 12 weeks (end of the study)
Brain biomarkers and psychological indicators of rTMS effects and pain relief
Test for objective mechanistic brain correlates (using functional magnetic resonance imaging - fMRI) for treatment efficacy. Specific regions of interest (ROI) involved in the hippocampal network will be studied.
Measured: 1 to 12 weeks (end of the study)
Adverse events
Incidence of adverse events will be reported for after each rTMS session.The frequency and severity of adverse effects will be compared between each rTMS modality.
Measured: 1 to 12 weeks (end of the study)
Global impression of change
Global impression of change (PGIC): this questionnaire reflects a patient's belief about the efficacy of treatment. Although widely used in chronic pain clinical trials, PGIC's validity has not been formally assessed. PGIC is a 7 point scale depicting a patient's rating of overall improvement.
Measured: 1 to 12 weeks - after each rTMS round.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2021
- Study start15 Nov 2021
- Primary completion1 Dec 2022
- Study completion1 Jan 2023
Why it stopped: Preliminary data in chronic back pain patients showed no benefits of the treatment; we did not further pursue the same treatment in osteoarthritis patients.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic PainStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- 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).
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Apkar Apkarian, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05097729
- Sponsor's protocol ID
- STU00214446
- Status last verified
- Feb 2023
- First submitted
- 18 Oct 2021
- Last updated
- 3 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcranial Magnetic Stimulation to Enhance Cortical Hippocampal Functional Connectivity as a Novel Means for Relieving Chronic OA Pain
- ClinicalTrials.gov ID
- NCT05097729
- Acronym / sponsor ID
- STU00214446
- Conditions
- Chronic Pain, Osteo Arthritis Knee
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Preliminary data in chronic back pain patients showed no benefits of the treatment; we did not further pursue the same treatment in osteoarthritis patients.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Study start
- 15 Nov 2021 (actual)
- Primary completion
- 1 Dec 2022 (actual)
- Study completion
- 1 Jan 2023 (actual)
- First posted
- 28 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 3
- 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).
| Arm | Type | Receives |
|---|---|---|
| Stimulation Modality 1 | Experimental | Device: Transcranial Magnetic StimulationRepetitive TMS will be applied at 100% resting motor threshold intensity to a region of interest located in the parietal cortex, that will be determined based on its connectivity with the hippocampus. |
| Stimulation Modality 2 | Sham comparator | Device: Transcranial Magnetic StimulationParameters will be identical to the modality 1, except that the coil will be flipped over. |
| Stimulation Modality 3 | Active comparator | Device: Transcranial Magnetic StimulationThe stimulation will be delivered over the motor cortex contralateral to the predominant painful region, i.e., right motor cortex stimulation if left knee pain. The stimulation intensity will be set at 80% of the resting motor threshold. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- ≥ 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;
Key exclusion criteria (13 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcranial Magnetic StimulationAlso: TMSThe brain stimulation can be delivery using different devices; in this project a MagPro X100 stimulator connected to a MagPro Cool-B65 liquid-cooled butterfly coil (MagVenture A/S, Farum, Denmark) will be used. Resting motor threshold (M1-rTMS) will be determined during the visit 1 or visit 2 and used along all visits. The rTMS pulse sequences and intensities used are all within the published safety guidelines | Device | Stimulation Modality 1, Stimulation Modality 2, Stimulation Modality 3 |
Primary outcome
Pain ratings (Numeric Rating Scale)
Time frame: Pain ratings immediately after each rTMS modality and effects after the end of stimulation round (1 week).
The primary efficacy outcomes are the effects of the rTMS modalities on pain app ratings.
4 secondary outcomes
Pain trajectories
Time frame: 1 to 12 weeks (end of the study)
Brain biomarkers and psychological indicators of rTMS effects and pain relief
Time frame: 1 to 12 weeks (end of the study)
Adverse events
Time frame: 1 to 12 weeks (end of the study)
Global impression of change
Time frame: 1 to 12 weeks - after each rTMS round.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2023.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial Magnetic Stimulation in people with Chronic Pain and Osteo Arthritis Knee, run by Northwestern University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 3 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pain ratings (Numeric Rating Scale) (time frame: Pain ratings immediately after each rTMS modality and effects after the end of stimulation round (1 week).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2023.