NCT07791966

Brief 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. 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:

  1. 1.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.
  2. 2.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.
  3. 3.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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at below P25 for not_applicable

Timeline
26mo left

Started Oct 2026

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 18, 2026

Completed
10 days until next milestone

First Posted

Study publicly available on registry

August 28, 2026

Completed
1 month until next milestone

Study Start

First participant enrolled

October 1, 2026

Expected
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 31, 2028

3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2028

Last Updated

August 28, 2026

Status Verified

August 1, 2026

Enrollment Period

1.9 years

First QC Date

August 18, 2026

Last Update Submit

August 26, 2026

Conditions

Complex Regional Pain Syndrome (CRPS)

Outcome Measures

Primary Outcomes (1)

  • 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.

    Periprocedural

Secondary Outcomes (2)

  • standard deviation in R-R length

    Periprocedural

  • number of spontaneous skin conductance fluctuations

    Periprocedural

Study Arms (2)

alpha frequency tACS

EXPERIMENTAL
Device: transcranial alternating current stimulation (tACS)

gamma frequency tACS

ACTIVE COMPARATOR
Device: transcranial alternating current stimulation (tACS)

Interventions

transcranial alternating current stimulation (tACS)DEVICE

Real tACS will stimulate the brain in the individual alpha frequency (8-12 Hz) measured from baseline MEG

alpha frequency tACS

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age 18 years or older
  • Diagnosed with Complex Regional Pain Syndrome (CRPS) Type I or II, based on Budapest criteria
  • 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)

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

Related Publications (3)

  • 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.

    PMID: 40668023BACKGROUND

  • Malan 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.

    PMID: 41207412BACKGROUND

  • Gopalakrishnan 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.

    PMID: 42504856BACKGROUND

MeSH Terms

Conditions

Complex Regional Pain Syndromes

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Autonomic Nervous System DiseasesNervous System DiseasesPeripheral Nervous System DiseasesNeuromuscular Diseases

Intervention Hierarchy (Ancestors)

Electric Stimulation TherapyTherapeuticsConvulsive TherapyPsychiatric Somatic TherapiesBehavioral Disciplines and ActivitiesElectroshockPsychological Techniques

Central Study Contacts

Raghavan Gopalakrishnan

CONTACT

2164459322gopalar@ccf.org

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Staff

Study Record Dates

First Submitted

August 18, 2026

First Posted

August 28, 2026

Study Start (Estimated)

October 1, 2026

Primary Completion (Estimated)

August 31, 2028

Study Completion (Estimated)

December 1, 2028

Last Updated

August 28, 2026

Record last verified: 2026-08

Data Sharing

IPD Sharing
Will share

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.

Locations

US(1)