Complex Regional Pain Syndrome (CRPS)NCT07791966
Effects of Non-invasive Brain Stimulation on Pain Avoidance Behavior in Chronic Pain Patients
A study testing transcranial alternating current stimulation (tACS) in people with Complex Regional Pain Syndrome (CRPS), run by The Cleveland Clinic at 1 site in United States.
Trial summary
Pain avoidance helps with survival. However, chronic pain patients often avoid valued life activities fearing onset or exacerbation of pain. Hence, pain avoidance no longer protects, but reduces quality of life. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Complex Regional Pain Syndrome (CRPS)
- What is being tested?
- transcranial alternating current stimulation (tACS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2026to Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years or older
- Diagnosed with Complex Regional Pain Syndrome (CRPS) Type I or II, based on Budapest criteria
- 6 months or more of medically refractory severe pain
- Average daily pain for past 30 days >= 5 on 0-10 scale
- Presence of allodynia and/or hyperalgesia
- Lower extremity CRPS: bilateral or unilateral pain
- Not concurrently treated with neurostimulation therapies such as spinal cord stimulators (SCS)
- Absence of co-occurring severe psychiatric disorders (PHQ-9<19 and/or GAD-7<14)
Who cannot join
- Age under 18 years, pregnant women of any age
- Any co-occurring pain diagnosis that might confound with allodynia/hyperalgesia resulting from CRPS reflecting a malfunction in sensory processing within the CNS.
- Less than six months of medically refractory pain
- Average daily pain for past 30 days <5 on 0-10 scale
- Absence of allodynia and/or hyperalgesia
- Concurrent neurostimulation therapies such as SCS
- Severe disorders or conditions (e.g., cardiovascular, liver issues), terminal illness
- PHQ-9>19 and/or GAD-7>14 (severe depression/anxiety)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Cleveland Clinic
Cleveland, Ohio, 44195
Raghavan Gopalakrishnan, 800-223-2273, gopalar@ccf.org
About this study
Official title: Alpha tACS and Pain Avoidance Behavior in Chronic Pain Patients
Pain avoidance helps with survival. However, chronic pain patients often avoid valued life activities fearing onset or exacerbation of pain. Hence, pain avoidance no longer protects, but reduces quality of life. The goal of this clinical trial is to learn if non-invasive brain stimulation technique called transcranial alternating current stimulation (tACS) impact pain avoidance behavior in chronic pain patients. tACS is a way to gently stimulate the brain using a small, portable device. It sends an extremely weak, continuous alternating current through the scalp. Participants will either get real tACS or a fake (sham) version. Real tACS will stimulate the brain in the alpha frequency (8-12 Hz) which has been found to influence pain avoidance behavior, whereas sham tACS will stimulate the brain in a different frequency that is not known to influence avoidance behavior. The main questions it aims to answer are:
Does tACS alter the way chronic pain patients confront pain in terms of avoidance behavior? How does tACS impact brain signals related to pain avoidance behavior?
Read more
Participants will:
- fill out self-administered questionnaires asking about their medication use, personality and temperament, mood, including anxiety and depression, current pain level, and any disability you have due to your pain.
- perform of a pain avoidance task before, during and after 'real' tACS or 'sham' tACS. They may also be asked to stay quiet before, during and after tACS. During this period, we will scan the brain using a neuroimaging device called Magnetoencephalography (MEG). Additionally, Electroencephalography (EEG) brain signals will also be collected using electrodes affixed to the scalp. We may also measure Skin conductance response (SCR) and electrocardiography (EKG) using electrodes affixed to the skin.
- also get a T1 MRI if they do not have an implanted SCS, DRG, intrathecal pump, or other similar device that are not MRI compatible.
- Conditions
- Complex Regional Pain Syndrome (CRPS)
- Being tested
- transcranial alternating current stimulation (tACS)
- Medical subject headings
- Complex Regional Pain Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
transcranial alternating current stimulation (tACS)Device
Real tACS will stimulate the brain in the individual alpha frequency (8-12 Hz) measured from baseline MEG
transcranial alternating current stimulation (tACS)Device
active control tACS will stimulate the brain at 40Hz
| Study group | Role | What they receive |
|---|---|---|
| alpha frequency tACS | Experimental | Not described Receives: Device: transcranial alternating current stimulation (tACS) |
| gamma frequency tACS | Active comparator | Not described Receives: Device: transcranial alternating current stimulation (tACS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
magnitude of alpha frequency band power
measured using MEG/EEG from resting-state and during the performance of pain avoidance task. The MEG/EEG neural signals will be transformed to frequency domain to measure the magnitude of power in the alpha band.
Measured: Periprocedural
Secondary outcomes (2)
standard deviation in R-R length
standard deviation in R-R length (SDNN), a measure of heart rate variability from RR interval tachogram derived from EKG.
Measured: Periprocedural
number of spontaneous skin conductance fluctuations
number of spontaneous skin conductance fluctuations will be measured from galvanic skin conductance response time-series data.
Measured: Periprocedural
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2026
- Study start1 Oct 2026 (estimated)
- Primary completion31 Aug 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Complex Regional Pain Syndrome (CRPS)Studies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe 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
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH)
- Responsible party
- Principal investigator, Raghavan Gopalakrishnan, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07791966
- Sponsor's protocol ID
- 26-220
- Other IDs
- R21AT013595
- Status last verified
- Aug 2026
- First submitted
- 18 Aug 2026
- Last updated
- 28 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: De-identified individual participant data underlying the results reported in publications, along with relevant study documentation and analytic code, may be shared with qualified researchers upon reasonable request to the study investigators. Data will be available following publication of the primary study results, subject to applicable institutional policies, informed consent provisions, and execution of an appropriate data use agreement.
Publications
Gopalakrishnan R, Sonneborn C, Baillet S, Machado AG, Wager TD, Roy M. Neurophysiological encoding of aversive prediction errors. Pain. 2025 Dec 1;166(12):e732-e745. doi: 10.1097/j.pain.0000000000003712. Epub 2025 Jul 16.
PubMed 40668023Malan NS, Baillet S, Tankha P, Roy M, Gopalakrishnan R. Altered cortical alpha modulations and connectivity in complex regional pain syndrome. J Pain. 2026 Feb;39:105595. doi: 10.1016/j.jpain.2025.105595. Epub 2025 Nov 7.
PubMed 41207412Gopalakrishnan R, Malan NS, Sonneborn C, Hogue O, Tankha P, Baillet S, Roy M. Mechanisms Underlying Pain Avoidance in Complex Regional Pain Syndrome. Eur J Pain. 2026 Aug;30(7):e70339. doi: 10.1002/ejp.70339.
PubMed 42504856
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Alpha tACS and Pain Avoidance Behavior in Chronic Pain Patients
- ClinicalTrials.gov ID
- NCT07791966
- Acronym / sponsor ID
- 26-220
- Conditions
- Complex Regional Pain Syndrome (CRPS)
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH)
- Study start
- 1 Oct 2026 (estimated)
- Primary completion
- 31 Aug 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 28 Aug 2026 (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.
Pain avoidance helps with survival. However, chronic pain patients often avoid valued life activities fearing onset or exacerbation of pain. Hence, pain avoidance no longer protects, but reduces quality of life. The goal of this clinical trial is to learn if non-invasive brain stimulation technique called transcranial alternating current stimulation (tACS) impact pain avoidance behavior in chronic pain patients. tACS is a way to gently stimulate the brain using a small, portable device. It sends an extremely weak, continuous alternating current through the scalp. Participants will either get real tACS or a fake (sham) version. Real tACS will stimulate the brain in the alpha frequency (8-12 Hz) which has been found to influence pain avoidance behavior, whereas sham tACS will stimulate the brain in a different frequency that is not known to influence avoidance behavior. The main questions it aims to answer are:
Does tACS alter the way chronic pain patients confront pain in terms of avoidance behavior? How does tACS impact brain signals related to pain avoidance behavior?
Participants will:
- fill out self-administered questionnaires asking about their medication use, personality and temperament, mood, including anxiety and depression, current pain level, and any disability you have due to your pain.
- perform of a pain avoidance task before, during and after 'real' tACS or 'sham' tACS. They may also be asked to stay quiet before, during and after tACS. During this period, we will scan the brain using a neuroimaging device called Magnetoencephalography (MEG). Additionally, Electroencephalography (EEG) brain signals will also be collected using electrodes affixed to the scalp. We may also measure Skin conductance response (SCR) and electrocardiography (EKG) using electrodes affixed to the skin.
- also get a T1 MRI if they do not have an implanted SCS, DRG, intrathecal pump, or other similar device that are not MRI compatible.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| alpha frequency tACS | Experimental | Device: transcranial alternating current stimulation (tACS) |
| gamma frequency tACS | Active comparator | Device: transcranial alternating current stimulation (tACS) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age 18 years or older
- Diagnosed with Complex Regional Pain Syndrome (CRPS) Type I or II, based on Budapest criteria
- 6 months or more of medically refractory severe pain
- Average daily pain for past 30 days >= 5 on 0-10 scale
- Presence of allodynia and/or hyperalgesia
Key exclusion criteria (8 listed)
- Age under 18 years, pregnant women of any age
- Any co-occurring pain diagnosis that might confound with allodynia/hyperalgesia resulting from CRPS reflecting a malfunction in sensory processing within the CNS.
- Less than six months of medically refractory pain
- Average daily pain for past 30 days <5 on 0-10 scale
- Absence of allodynia and/or hyperalgesia
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 alternating current stimulation (tACS)Real tACS will stimulate the brain in the individual alpha frequency (8-12 Hz) measured from baseline MEG | Device | alpha frequency tACS |
| transcranial alternating current stimulation (tACS)active control tACS will stimulate the brain at 40Hz | Device | gamma frequency tACS |
Primary outcome
magnitude of alpha frequency band power
Time frame: Periprocedural
measured using MEG/EEG from resting-state and during the performance of pain avoidance task. The MEG/EEG neural signals will be transformed to frequency domain to measure the magnitude of power in the alpha band.
2 secondary outcomes
standard deviation in R-R length
Time frame: Periprocedural
number of spontaneous skin conductance fluctuations
Time frame: Periprocedural
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2026.
- Background: PubMed 40668023Gopalakrishnan R, Sonneborn C, Baillet S, Machado AG, Wager TD, Roy M. Neurophysiological encoding of aversive prediction errors. Pain. 2025 Dec 1;166(12):e732-e745. doi: 10.1097/j.pain.0000000000003712. Epub 2025 Jul 16.
- Background: PubMed 41207412Malan NS, Baillet S, Tankha P, Roy M, Gopalakrishnan R. Altered cortical alpha modulations and connectivity in complex regional pain syndrome. J Pain. 2026 Feb;39:105595. doi: 10.1016/j.jpain.2025.105595. Epub 2025 Nov 7.
- Background: PubMed 42504856Gopalakrishnan R, Malan NS, Sonneborn C, Hogue O, Tankha P, Baillet S, Roy M. Mechanisms Underlying Pain Avoidance in Complex Regional Pain Syndrome. Eur J Pain. 2026 Aug;30(7):e70339. doi: 10.1002/ejp.70339.
- Individual participant dataSharing planned: Yes. De-identified individual participant data underlying the results reported in publications, along with relevant study documentation and analytic code, may be shared with qualified researchers upon reasonable request to the study investigators. Data will be available following publication of the primary study results, subject to applicable institutional policies, informed consent provisions, and execution of an appropriate data use agreement.
Related trials for Complex Regional Pain Syndrome (CRPS)
RecruitingPhase 3
Evaluation of IV AMBTX-01 (Neridronate) for Treatment of CRPS Type 1 (CRPS-RISE)
Complex Regional Pain Syndrome Type I
Recruiting
The Effectiveness of Conservative Treatment in Patients With Complex Regional Pain Syndrome.
CRPS (Complex Regional Pain Syndromes)
RecruitingPhase 3
Phase 3, Open-Label Extension Study of AMBTX-01 (Neridronate) for Complex Regional Pain Syndrome Type 1
Complex Regional Pain Syndrome Type I
Active, not recruiting
Transcranial Magnetic Stimulation for Chronic Neuropathic Pain
Chronic Neuropathic Pain, Post-Stroke Pain
Recruiting
Clinical and Cerebral Changes Following Multifaceted Rehabilitation of Complex Regional Pain Syndrome
Complex Regional Pain Syndrome (CRPS)
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.
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 alternating current stimulation (tACS) in people with Complex Regional Pain Syndrome (CRPS), run by The Cleveland Clinic 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 8 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: looking for participants now, as of the sponsor's last update on 28 Aug 2026. 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. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Raghavan Gopalakrishnan (2164459322, gopalar@ccf.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
magnitude of alpha frequency band power (time frame: Periprocedural). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07791966, which also lists 3 linked publications.
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 28 Aug 2026.