Opioid Use DisorderTMSNCT03821337
Transcranial Magnetic Stimulation (rTMS) as a Tool to Decrease Pain and Improve Functioning
A study testing repetitive Trans Magnetic Stimulation in people with Opioid Use Disorder, run by VA Office of Research and Development at 1 site in United States.
Trial summary
Despite the availability of opioid replacement therapies, many opioid use disordered Veterans are not able to remain abstinent. Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive neuromodulation technique with a consistent, rapidly expanding literature base reporting positive outcomes in substance… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Opioid Use Disorder
- What is being tested?
- repetitive Trans Magnetic Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Oct 2019to 31 Dec 2021
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must be able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments.
- Participants must meet moderate to severe DSM-5 criteria for OUD. While individuals may also meet criteria for use disorders of other substances (with the exception of alcohol or benzodiazepines), they must identify opioids as their primary substance of abuse.
- Participants must report chronic pain for at least the past three months and have a Brief Pain Inventory score.
- Participants must be receiving treatment through the STAR program.
Who cannot join
- Participants who are pregnant.
- Participants with a history of/or current psychotic disorder.
- Participants with a history of dementia or other cognitive impairment.
- Participants with active suicidal ideation, or a suicide attempt within the past 90 days will be excluded.
- Participants with contraindications to receiving rTMS (including a history of seizures, or any implanted metal above the neck).
- Those with unstable general medical conditions.
- Those who are currently using naltrexone or tramadol.
- Those with current alcohol or benzodiazepine use disorders due to increased risk of seizure.
Trial locations and contacts
1 site in 1 country.
United States1 site
Ralph H. Johnson VA Medical Center, Charleston, SC
Charleston, South Carolina, 29401-5799
About this study
Official title: An Exploratory Investigation Utilizing Repetitive Transcranial Magnetic Stimulation (rTMS) as a Tool to Decrease Pain and Improve Functioning in Veterans With Opioid Use Disorder
Despite the availability of opioid replacement therapies, many opioid use disordered Veterans are not able to remain abstinent. Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive neuromodulation technique with a consistent, rapidly expanding literature base reporting positive outcomes in substance using populations. This pilot application will investigate a novel multi-session rTMS paradigm to determine feasibility and tolerability of this intervention in opioid use disordered Veterans.
Read the detailed description
Opioid use disorders (OUDs) are common among Veterans. Despite the availability of opioid replacement therapies, many individuals continue to abuse opioids and relapse rates remain high. Veterans are nearly twice as likely to die from accidental opioid overdose than the general population. Approximately 60% of Veterans returning from the Middle East and more than 50% of older Veterans in the VA health care system have chronic pain. Further, post-traumatic stress disorder, a common comorbidity in the Veteran population, has been shown to negatively impact early engagement and retention of individuals in OUD treatment. As is the case with other substance use disorders, opioid craving is commonly described by abstinent patients whether or not they are stabilized on buprenorphine. Subsequently, a treatment that reduces pain and craving, while also improving early engagement and retention in treatment, would improve recovery from opioid addiction. Repetitive Transcranial Magnetic Stimulation (rTMS) is capable of non-invasively altering cortical function. rTMS is an FDA-approved treatment for major depressive disorder. Preliminary evidence suggests that rTMS can also reduce pain in chronic pain conditions and craving in substance use disorders. Single sessions of rTMS produce small temporary effects, while multiple sessions of rTMS result in larger, more durable effects. The investigators' group recently completed a blinded, sham-controlled crossover trial in non-treatment seeking OUD participants. A single session of rTMS reduced cue-induced craving and increased thermal pain thresholds. Given that multiple sessions of rTMS produce larger and more durable treatment effects than single sessions of rTMS, it follows that multiple treatment sessions applied to OUD patients may result in a clinically relevant reduction in pain and cue-induced craving, which could improve clinical and functional outcomes.
In this SPiRE pilot proposal, the investigators will perform a randomized, double-blind, sham-controlled trial delivering an accelerated course of rTMS to a cohort of OUD Veterans with chronic pain receiving treatment through the Ralph H. Johnson VA Medical Center Substance Treatment and Recovery program. The goal of this proposal is to evaluate the feasibility and acceptability of delivering rTMS to the dorsolateral pre-frontal cortex in Veterans with OUD and chronic pain. The investigators will also preliminarily explore the feasibility of evaluating potential outcome measurements in preparation for a larger trial, including abstinence, treatment retention, community reintegration and functional outcomes, pain, and opioid craving. Positive results from this pilot project will inform a future MERIT application and have the potential to significantly improve treatment outcomes in this difficult to treat Veteran population.
- Conditions
- Opioid Use Disorder
- Being tested
- repetitive Trans Magnetic Stimulation, Sham TMS
- Keywords
- Opioid use disorder
- Medical subject headings
- Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
repetitive Trans Magnetic StimulationDevice
Also called rTMS
Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that is able to alter cortical excitability and is FDA-approved to treat Major Depressive Disorder. Magnetic fields pass unimpeded through the scalp, skull and meninges, and can directly excite cortical areas.
Sham TMSDevice
Sham sessions will be delivered using an electronic sham system consisting of a coil that mimics the appearance and sound of TMS, combined with a TENS device which produces a small electric shock mimicking the feeling of real rTMS. This type of sham has been demonstrated to be indistinguishable from real rTMS, has been well tolerated (George et al., 2010; George et al., 2014) and successfully used in other clinical trials (Borckardt et al., 2008; Arana et al., 2008). During each session of rTMS the investigators will present a series of opioid related images, including those utilized in previous studies (Garland et al., 2015; Garland \& Howard, 2014).
| Study group | Role | What they receive |
|---|---|---|
| rTMS | Experimental | Participants will receive 18 sessions of active rTMS delivered at 120% rMT. Receives: Device: repetitive Trans Magnetic Stimulation |
| Sham TMS | Placebo comparator | Participants will receive 18 sessions of sham rTMS delivered through an inactive coil. Receives: Device: Sham TMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Retention: Total Number of rTMS Sessions Completed
Total number of rTMS sessions completed out of 6 sessions per day for three days over a three week period.
Measured: Through study completion, an average of 3 weeks
Tolerability: The Total Number of Treatment Emergent Adverse Events
Number of adverse events experienced by Veterans receiving medication assisted treatment for opioid use disorder who undergo 18 sessions of active or sham rTMS.
Measured: Through study completion, an average of 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2019
- Study start11 Oct 2019
- Primary completion31 Dec 2021
- Study completion31 Dec 2021
Why it stopped: COVID-19 placed all Charleston VA projects on hold. Recently gained approval to open studies with COVID-19 precautions
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Opioid Use DisorderStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe 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
- Parallel groups
- Model description
- Double-blind, Randomized, Placebo-Controlled Trial
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Aimee L. Mcrae-Clark, PharmD, Principal investigator, Ralph H. Johnson VA Medical Center, Charleston, SC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03821337
- Sponsor's protocol ID
- D3006-P
- Other IDs
- RX003006, Pro00084970
- Acronym
- TMS
- Status last verified
- Nov 2022
- First submitted
- 28 Jan 2019
- Last updated
- 21 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Investigation Utilizing Repetitive Transcranial Magnetic Stimulation (rTMS) as a Tool to Decrease Pain and Improve Functioning in Veterans With Opioid Use Disorder
- ClinicalTrials.gov ID
- NCT03821337
- Acronym / sponsor ID
- TMS / D3006-P
- Conditions
- Opioid Use Disorder
- Keywords
- Opioid use disorder
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: COVID-19 placed all Charleston VA projects on hold. Recently gained approval to open studies with COVID-19 precautions
- Enrolment
- 1 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 11 Oct 2019 (actual)
- Primary completion
- 31 Dec 2021 (actual)
- Study completion
- 31 Dec 2021 (actual)
- First posted
- 29 Jan 2019 (actual)
- Results
- Posted 21 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Despite the availability of opioid replacement therapies, many opioid use disordered Veterans are not able to remain abstinent. Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive neuromodulation technique with a consistent, rapidly expanding literature base reporting positive outcomes in substance using populations. This pilot application will investigate a novel multi-session rTMS paradigm to determine feasibility and tolerability of this intervention in opioid use disordered Veterans.
Detailed description
Opioid use disorders (OUDs) are common among Veterans. Despite the availability of opioid replacement therapies, many individuals continue to abuse opioids and relapse rates remain high. Veterans are nearly twice as likely to die from accidental opioid overdose than the general population. Approximately 60% of Veterans returning from the Middle East and more than 50% of older Veterans in the VA health care system have chronic pain. Further, post-traumatic stress disorder, a common comorbidity in the Veteran population, has been shown to negatively impact early engagement and retention of individuals in OUD treatment. As is the case with other substance use disorders, opioid craving is commonly described by abstinent patients whether or not they are stabilized on buprenorphine. Subsequently, a treatment that reduces pain and craving, while also improving early engagement and retention in treatment, would improve recovery from opioid addiction. Repetitive Transcranial Magnetic Stimulation (rTMS) is capable of non-invasively altering cortical function. rTMS is an FDA-approved treatment for major depressive disorder. Preliminary evidence suggests that rTMS can also reduce pain in chronic pain conditions and craving in substance use disorders. Single sessions of rTMS produce small temporary effects, while multiple sessions of rTMS result in larger, more durable effects. The investigators' group recently completed a blinded, sham-controlled crossover trial in non-treatment seeking OUD participants. A single session of rTMS reduced cue-induced craving and increased thermal pain thresholds. Given that multiple sessions of rTMS produce larger and more durable treatment effects than single sessions of rTMS, it follows that multiple treatment sessions applied to OUD patients may result in a clinically relevant reduction in pain and cue-induced craving, which could improve clinical and functional outcomes.
In this SPiRE pilot proposal, the investigators will perform a randomized, double-blind, sham-controlled trial delivering an accelerated course of rTMS to a cohort of OUD Veterans with chronic pain receiving treatment through the Ralph H. Johnson VA Medical Center Substance Treatment and Recovery program. The goal of this proposal is to evaluate the feasibility and acceptability of delivering rTMS to the dorsolateral pre-frontal cortex in Veterans with OUD and chronic pain. The investigators will also preliminarily explore the feasibility of evaluating potential outcome measurements in preparation for a larger trial, including abstinence, treatment retention, community reintegration and functional outcomes, pain, and opioid craving. Positive results from this pilot project will inform a future MERIT application and have the potential to significantly improve treatment outcomes in this difficult to treat Veteran population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Double-blind, Randomized, Placebo-Controlled Trial
| Arm | Type | Receives |
|---|---|---|
| rTMS | Experimental | Device: repetitive Trans Magnetic StimulationParticipants will receive 18 sessions of active rTMS delivered at 120% rMT. |
| Sham TMS | Placebo comparator | Device: Sham TMSParticipants will receive 18 sessions of sham rTMS delivered through an inactive coil. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Participants must be able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments.
- Participants must meet moderate to severe DSM-5 criteria for OUD. While individuals may also meet criteria for use disorders of other substances (with the exception of alcohol or benzodiazepines), they must identify opioids as their primary substance of abuse.
- Participants must report chronic pain for at least the past three months and have a Brief Pain Inventory score.
- Participants must be receiving treatment through the STAR program.
Key exclusion criteria (8 listed)
- Participants who are pregnant.
- Participants with a history of/or current psychotic disorder.
- Participants with a history of dementia or other cognitive impairment.
- Participants with active suicidal ideation, or a suicide attempt within the past 90 days will be excluded.
- Participants with contraindications to receiving rTMS (including a history of seizures, or any implanted metal above the neck).
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 |
|---|---|---|
| repetitive Trans Magnetic StimulationAlso: rTMSRepetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that is able to alter cortical excitability and is FDA-approved to treat Major Depressive Disorder. Magnetic fields pass unimpeded through the scalp, skull and meninges, and can directly excite cortical areas. | Device | rTMS |
| Sham TMSSham sessions will be delivered using an electronic sham system consisting of a coil that mimics the appearance and sound of TMS, combined with a TENS device which produces a small electric shock mimicking the feeling of real rTMS. This type of sham has been demonstrated to be indistinguishable from real rTMS, has been well tolerated (George et al., 2010; George et al., 2014) and successfully used in other clinical trials (Borckardt et al., 2008; Arana et al., 2008). During each session of rTMS the investigators will present a series of opioid related images, including those utilized in previous studies (Garland et al., 2015; Garland \& Howard, 2014). | Device | Sham TMS |
Primary outcome
Retention: Total Number of rTMS Sessions Completed
Time frame: Through study completion, an average of 3 weeks
Total number of rTMS sessions completed out of 6 sessions per day for three days over a three week period.
Tolerability: The Total Number of Treatment Emergent Adverse Events
Time frame: Through study completion, an average of 3 weeks
Number of adverse events experienced by Veterans receiving medication assisted treatment for opioid use disorder who undergo 18 sessions of active or sham rTMS.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Aimee L. Mcrae-Clark, PharmD principal investigator
Ralph H. Johnson VA Medical Center, Charleston, SC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing repetitive Trans Magnetic Stimulation in people with Opioid Use Disorder, run by VA Office of Research and Development 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 4 inclusion and 8 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: stopped early, as of the sponsor's last update on 21 Dec 2022. 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?
Yes. Results are posted in the registry (first posted 21 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Retention: Total Number of rTMS Sessions Completed (time frame: Through study completion, an average of 3 weeks). The study lists 2 primary outcomes in all. 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 21 Dec 2022.