Using Neurostimulation to Accelerate Change in Misophonia: a Pilot Study

NCT ID: NCT06333925

Last Updated: 2025-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-05-14

Study Completion Date

2026-11-30

Brief Summary

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Misophonia, the inability to tolerate certain repetitive distressing sounds that are common, is gaining, recognition as an impairing condition. It is not a well-understood condition and there are no known treatments. The purpose of this study is to test a new misophonia intervention that uses emotion regulation strategies and different types of brain stimulation on misophonic distress. This study will examine changes in brain activity during presentation and regulation of misophonic versus distressing sounds. The study team plans to alter activity in a key area of the brain responsible for emotion regulation circuitry over 4 sessions with the goal to test if this intervention helps misophonic distress.

Sixty adult participants with moderate to severe misophonia will be recruited and taught an emotion regulation skill and randomly assigned to receive one of two types of repetitive transcranial magnetic stimulation (rTMS). The study includes 9-10 visits: the remote screening visit(s), the initial MRI, the four neurostimulation sessions, the follow-up MRI, and two additional remote 1- and 3-month follow-up visits.

Detailed Description

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Given the urgent need for interventions for misophonia, the primary purpose of this study is to establish short and long-term effects for an intervention that combines emotion regulation with neurostimulation. The secondary goal is to examine the best parameters needed for a successful intervention. It is important to highlight that the study findings would not only inform future behavioral and neurostimulation interventions but may also provide critical information for other intervention approaches that aim to alter neural circuitry involved in misophonia.

Interested participants who pass the online and phone screen are scheduled for the first study visit that will be conducted remotely. Those who are interested and provide e-consent, will complete demographic questions and several interviews and measures aimed to examine misophonic and psychiatric distress, verbal IQ, treatment history, and MRI/neurostimulation safety. Participants will listen to a set of standardized aversive and misophonic sounds and rate how distressing they find them. They will also be invited to send recordings of their own misophonic sounds in different contexts and together with them and other standardized misophonic sounds, they will listen to the sounds and rate their distress. The goal in the study is to generate a personalized set of triggers that includes personalized misophonic, aversive and neutral sounds for each participant.

The type of neuromodulation that is being tested in the study is repetitive transcranial magnetic stimulation (rTMS), a procedure which involves placement of an electromagnetic coil over the scalp that produces very small electric currents in the part of the brain that is closest to the coil. rTMS is a noninvasive procedure that is currently approved by the Food and Drug Administration (FDA) for the treatment for depression, obsessive compulsive disorder, and smoking. In this study, rTMS will be used differently than what has been approved for by the FDA but within safety guidelines.

The goal of the study is to enroll sixty eligible adult participants with misophonia who will then be asked to come to Duke for the initial brain MRI visit. Following established procedures, participants will be briefly taught CR (cognitive restructuring), an emotion regulation strategy selected because it successfully adjusts the emotion regulation network. Participants will undergo a functional neuroimaging (MRI) task based on which a personalized neurostimulation target will be established.

Participants will then be randomly assigned to active or sham rTMS intervention matching on age, gender at birth and misophonia impairment severity. Participants will then undergo four consecutive intervention sessions during which they will receive either type of rTMS over their personalized target on the right side of the brain while being exposed to personalized misophonic cues and instructed to engage in cognitive emotion regulation. At the initial TMS visit, all participants will be trained in CR in depth using a standardized training session. During each neurostimulation session, biophysiological data including heart rate and skin conductance will be collected.

A week after the intervention, participants will undergo a follow up MRI brain scan and will complete some of the questionnaires from the first visit regarding misophonia, mood, anxiety, difficulties managing emotions, general health and distress.

Two additional remote follow-up visits will be scheduled at the 1- and 3-month follow-up time points. Participants will complete the remote sound task similar to the first remote study visit. Measures of misophonia, mood, anxiety, difficulties managing emotions, general health and distress will again be assessed. At the final 3-month follow-up visit, participants will also complete an exit interview to give feedback on their study participation. As part of the exit interview, a member of the study team will inform the participant what type of neurostimulation they received during the study and referrals will be provided, if applicable.

Conditions

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Misophonia Emotion Dysregulation Sensory Processing Disorder Auditory Over Responsivity Anxiety Disorder Sound Sensitivity

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

In regards to the neurostimulation used in the study, there will be two conditions, receiving either active or sham neurostimulation. Both conditions will receive behavioral training in cognitive restructuring (CR; a type of emotion regulation skill). Randomization procedures will match participants on age, gender at birth, and misophonia impairment severity.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors
All participants will engage in a behavioral training session (Cognitive Restructuring).

The study team member who will conduct the behavioral session will be kept blind to the type of neurostimulation the participant will receive. Participants will also be kept blinded to what neurostimulation they receive and their perception of what they received will be assessed at follow-up. The intervention provider will also be kept blind to the treatment condition to ensure non-biased administration of the intervention.

Participants will only be told about the type of neurostimulation at the end of the study to protect against different expectations

Study Groups

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Cognitive Restructuring + High Frequency Repetitive Transcranial Magnetic Stimulation (rTMS)

30 eligible participants will receive training in Cognitive Restructuring (CR). These participants will use CR while being exposed to misophonic trigger sounds and also receiving high frequency rTMS over their personalized right dorsal lateral prefrontal cortex (dlPFC) target. These participants will partake in short term and long term follow-up testing.

Group Type EXPERIMENTAL

High Frequency Repetitive Transcranial Magnetic Stimulation (HF rTMS)

Intervention Type DEVICE

10 Hz rTMS over the right dorsal lateral prefrontal cortex (dlPFC)

Cognitive Restructuring

Intervention Type BEHAVIORAL

Cognitive restructuring is a cognitive behavioral intervention through which participants learn how to think differently about misophonic sound triggers in order to feel less emotional arousal.

Cognitive Restructuring + Shame Repetitive Transcranial Magnetic Stimulation (rTMS)

30 eligible participants will receive training in Cognitive Restructuring (CR). These participants will use CR while being exposed to misophonic trigger sounds and also receiving placebo rTMS over their personalized right dorsal lateral prefrontal cortex (dlPFC) target. These participants will partake in short term and long term follow-up testing.

Group Type ACTIVE_COMPARATOR

Sham Repetitive Transcranial Magnetic Stimulation (sham- rTMS)

Intervention Type DEVICE

inactive rTMS over the right dorsolateral prefrontal cortex (dlPFC)

Cognitive Restructuring

Intervention Type BEHAVIORAL

Cognitive restructuring is a cognitive behavioral intervention through which participants learn how to think differently about misophonic sound triggers in order to feel less emotional arousal.

Interventions

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High Frequency Repetitive Transcranial Magnetic Stimulation (HF rTMS)

10 Hz rTMS over the right dorsal lateral prefrontal cortex (dlPFC)

Intervention Type DEVICE

Sham Repetitive Transcranial Magnetic Stimulation (sham- rTMS)

inactive rTMS over the right dorsolateral prefrontal cortex (dlPFC)

Intervention Type DEVICE

Cognitive Restructuring

Cognitive restructuring is a cognitive behavioral intervention through which participants learn how to think differently about misophonic sound triggers in order to feel less emotional arousal.

Intervention Type BEHAVIORAL

Other Intervention Names

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CR

Eligibility Criteria

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Inclusion Criteria

* 18-55
* verbal agreement to maintain dose of prescribed psychotropic medication (if any) and/or psychotherapy (if any) constant throughout the study, provided they are stable on it for the past 4 weeks (except exclusion medication and except if there is a medical emergency requiring changes in medication).
* DMQ Impairment score \>= 14

Exclusion Criteria

* current or past history of mania or psychosis; current hypomania
* verbal IQ\< 90 as per the NART
* not medically cleared for TMS or fMRI (such as taking medications known to reduce the seizure threshold such as Lithium, Clozaril, stimulants including the ADHD medications (e.g. Ritalin, Adderall), Wellbutrin/Buproprion, Provigil (Modafinil), Aminophylline, and Theophylline)
* DMQ Impairment score \< 14
* younger than 18 and older than 55
* pregnant
* high risk for suicide (defined as having attempted suicide in past 6 months; suicide attempt within the past 10 years with current ideation with plan or preferred method available)
* moderate/severe current alcohol or substance use disorder, or past severe alcohol use disorder
* unable to read, blind, or deaf, or unwilling to give consent
* cannot come to Duke for the in-person study visits
* current uncontrolled anorexia or other condition requiring hospitalization
* conditions associated with increased intracranial pressure, space occupying brain lesion, transient ischemic attack, cerebral aneurysm, dementia, Parkinson's or Huntington's disease, multiple sclerosis
* use of investigational drug or devices within 4 weeks of screening
* started/changed psychotropic medications or started psychotherapy in the prior 4 weeks, or plans to change medication or stop psychotherapy during the study
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Misophonia Research Fund

OTHER

Sponsor Role collaborator

Duke University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Andrada D Neacsiu, PhD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

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Duke University Medical Center

Durham, North Carolina, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Jessica Choi, MA

Role: CONTACT

919-684-4432

Lisalynn D Kelley, BA, CCRP

Role: CONTACT

919-684-6701

Facility Contacts

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Jessica Choi, MA

Role: primary

919-684-4432

Lisalynn D Kelley, BA, CCRP

Role: backup

919-684-6701

References

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Tsagaris KZ, Labar DR, Edwards DJ. A Framework for Combining rTMS with Behavioral Therapy. Front Syst Neurosci. 2016 Nov 15;10:82. doi: 10.3389/fnsys.2016.00082. eCollection 2016.

Reference Type BACKGROUND
PMID: 27895557 (View on PubMed)

Brout JJ, Edelstein M, Erfanian M, Mannino M, Miller LJ, Rouw R, Kumar S, Rosenthal MZ. Investigating Misophonia: A Review of the Empirical Literature, Clinical Implications, and a Research Agenda. Front Neurosci. 2018 Feb 7;12:36. doi: 10.3389/fnins.2018.00036. eCollection 2018.

Reference Type BACKGROUND
PMID: 29467604 (View on PubMed)

Kumar S, Tansley-Hancock O, Sedley W, Winston JS, Callaghan MF, Allen M, Cope TE, Gander PE, Bamiou DE, Griffiths TD. The Brain Basis for Misophonia. Curr Biol. 2017 Feb 20;27(4):527-533. doi: 10.1016/j.cub.2016.12.048. Epub 2017 Feb 2.

Reference Type BACKGROUND
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Neacsiu AD, Szymkiewicz V, Galla JT, Li B, Kulkarni Y, Spector CW. The neurobiology of misophonia and implications for novel, neuroscience-driven interventions. Front Neurosci. 2022 Jul 25;16:893903. doi: 10.3389/fnins.2022.893903. eCollection 2022.

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PMID: 35958984 (View on PubMed)

Schroder A, van Wingen G, Eijsker N, San Giorgi R, Vulink NC, Turbyne C, Denys D. Misophonia is associated with altered brain activity in the auditory cortex and salience network. Sci Rep. 2019 May 17;9(1):7542. doi: 10.1038/s41598-019-44084-8.

Reference Type BACKGROUND
PMID: 31101901 (View on PubMed)

Eijsker N, Schroder A, Smit DJA, van Wingen G, Denys D. Neural Basis of Response Bias on the Stop Signal Task in Misophonia. Front Psychiatry. 2019 Oct 23;10:765. doi: 10.3389/fpsyt.2019.00765. eCollection 2019.

Reference Type BACKGROUND
PMID: 31708818 (View on PubMed)

Kumar S, Dheerendra P, Erfanian M, Benzaquen E, Sedley W, Gander PE, Lad M, Bamiou DE, Griffiths TD. The Motor Basis for Misophonia. J Neurosci. 2021 Jun 30;41(26):5762-5770. doi: 10.1523/JNEUROSCI.0261-21.2021. Epub 2021 May 21.

Reference Type BACKGROUND
PMID: 34021042 (View on PubMed)

Enzler F, Loriot C, Fournier P, Norena AJ. A psychoacoustic test for misophonia assessment. Sci Rep. 2021 May 26;11(1):11044. doi: 10.1038/s41598-021-90355-8.

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PMID: 34040061 (View on PubMed)

Erfanian M, Kartsonaki C, Keshavarz A. Misophonia and comorbid psychiatric symptoms: a preliminary study of clinical findings. Nord J Psychiatry. 2019 May-Jul;73(4-5):219-228. doi: 10.1080/08039488.2019.1609086. Epub 2019 May 8.

Reference Type BACKGROUND
PMID: 31066600 (View on PubMed)

Neacsiu AD, Beynel L, Graner JL, Szabo ST, Appelbaum LG, Smoski MJ, LaBar KS. Enhancing cognitive restructuring with concurrent fMRI-guided neurostimulation for emotional dysregulation-A randomized controlled trial. J Affect Disord. 2022 Mar 15;301:378-389. doi: 10.1016/j.jad.2022.01.053. Epub 2022 Jan 14.

Reference Type BACKGROUND
PMID: 35038479 (View on PubMed)

Neacsiu AD, Beynel L, Powers JP, Szabo ST, Appelbaum LG, Lisanby SH, LaBar KS. Enhancing Cognitive Restructuring with Concurrent Repetitive Transcranial Magnetic Stimulation: A Transdiagnostic Randomized Controlled Trial. Psychother Psychosom. 2022;91(2):94-106. doi: 10.1159/000518957. Epub 2021 Sep 22.

Reference Type BACKGROUND
PMID: 34551415 (View on PubMed)

Mai S, Braun J, Probst V, Kammer T, Pollatos O. Changes in emotional processing following interoceptive network stimulation with rTMS. Neuroscience. 2019 May 15;406:405-419. doi: 10.1016/j.neuroscience.2019.03.014. Epub 2019 Mar 14.

Reference Type BACKGROUND
PMID: 30880101 (View on PubMed)

Luber B, Steffener J, Tucker A, Habeck C, Peterchev AV, Deng ZD, Basner RC, Stern Y, Lisanby SH. Extended remediation of sleep deprived-induced working memory deficits using fMRI-guided transcranial magnetic stimulation. Sleep. 2013 Jun 1;36(6):857-71. doi: 10.5665/sleep.2712.

Reference Type BACKGROUND
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Abdelrahman AA, Noaman M, Fawzy M, Moheb A, Karim AA, Khedr EM. A double-blind randomized clinical trial of high frequency rTMS over the DLPFC on nicotine dependence, anxiety and depression. Sci Rep. 2021 Jan 15;11(1):1640. doi: 10.1038/s41598-020-80927-5.

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PMID: 33452340 (View on PubMed)

Kleinjung T, Eichhammer P, Langguth B, Jacob P, Marienhagen J, Hajak G, Wolf SR, Strutz J. Long-term effects of repetitive transcranial magnetic stimulation (rTMS) in patients with chronic tinnitus. Otolaryngol Head Neck Surg. 2005 Apr;132(4):566-9. doi: 10.1016/j.otohns.2004.09.134.

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Somani A, Kar SK. Efficacy of repetitive transcranial magnetic stimulation in treatment-resistant depression: the evidence thus far. Gen Psychiatr. 2019 Aug 12;32(4):e100074. doi: 10.1136/gpsych-2019-100074. eCollection 2019.

Reference Type BACKGROUND
PMID: 31552384 (View on PubMed)

Other Identifiers

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Pro00114183

Identifier Type: -

Identifier Source: org_study_id

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