Neurostimulation for Misophonia

(MISO-STIM Trial)

Overseen By Andrada D Neacsiu, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Duke University

Must not be taking: Lithium, Clozaril, Stimulants, others

Disqualifiers: Mania, Psychosis, Substance use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 4 days

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore new ways to help people with misophonia, a condition where everyday sounds cause significant distress. Researchers will test whether a combination of emotion regulation techniques and brain stimulation (High Frequency Repetitive Transcranial Magnetic Stimulation, HF rTMS) can reduce this distress. Participants will be divided into two groups to receive either active or placebo brain stimulation, along with training to manage their emotional responses to triggering sounds. The trial seeks adults with moderate to severe misophonia who can attend several sessions. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to new treatments for misophonia.

Will I have to stop taking my current medications?

You can continue taking your current medications as long as they are not on the exclusion list and you have been stable on them for the past 4 weeks. You must keep the dose the same throughout the study unless there's a medical emergency.

What prior data suggests that this neurostimulation technique is safe for treating misophonia?

Research has shown that high-frequency repetitive transcranial magnetic stimulation (HF rTMS) is generally well-tolerated. One study found that participants receiving HF rTMS with cognitive restructuring experienced minimal side effects, suggesting the treatment can be safely administered.

Studies involving HF rTMS reported no serious health problems, indicating participants did not face major issues during or after sessions. Some individuals might feel mild discomfort or a tingling sensation at the stimulation site, but these effects are usually temporary.

Overall, HF rTMS appears promising in terms of safety, particularly for those exploring new treatments for conditions like misophonia. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the neurostimulation approach for tackling misophonia because it offers a novel mechanism of action. Unlike standard treatments, which often focus on therapy or medication to manage symptoms, high frequency repetitive transcranial magnetic stimulation (HF rTMS) directly targets brain regions involved in emotional regulation. By stimulating the right dorsal lateral prefrontal cortex, HF rTMS aims to reduce the intense emotional reactions triggered by specific sounds. Additionally, when combined with Cognitive Restructuring, this method offers a dual approach: reshaping thought patterns while rewiring brain activity, potentially providing a more comprehensive treatment option for patients.

What evidence suggests that this neurostimulation method is effective for misophonia?

This trial will compare the effects of High Frequency Repetitive Transcranial Magnetic Stimulation (HF rTMS) with Sham Repetitive Transcranial Magnetic Stimulation (sham-rTMS) in participants with misophonia. Studies have shown that HF rTMS can help people manage their emotions better, especially when dealing with distressing sounds like those experienced in misophonia. Specifically, HF rTMS has been associated with improved emotional responses to these sounds. Some research also suggests that HF rTMS might offer cognitive benefits, which could help with misophonia symptoms. Although most evidence comes from studies on other conditions, the success of this technique in addressing emotional and sound-related issues indicates it could be promising for misophonia. Overall, researchers remain hopeful about HF rTMS for treating misophonia because it changes brain activity to help regulate emotions. ^{1 3 5 6 7}

Who Is on the Research Team?

Andrada D Neacsiu, PhD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for adults with moderate to severe misophonia, which makes them highly sensitive to certain sounds. Participants should be able to attend 9-10 visits including MRI scans and follow-up sessions. Details on specific inclusion and exclusion criteria are not provided.

Inclusion Criteria

DMQ Impairment score >= 14

Trigger sounds include mouth/throat sounds

I agree to keep my mental health treatment the same during the study.

Exclusion Criteria

Cannot come to Duke for the in-person study visits

I have recently started or changed my mental health medication or therapy.

Pregnant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Remote screening visit(s)

Initial Assessment

Participants undergo an initial MRI and are taught an emotion regulation skill

1 day

1 visit (in-person)

Treatment

Participants receive four sessions of rTMS while engaging in cognitive emotion regulation

4 days

4 visits (in-person)

Follow-up

Participants undergo a follow-up MRI and complete questionnaires on misophonia and emotional regulation

1 week after treatment

1 visit (in-person)

Long-term Follow-up

Participants complete remote follow-up visits at 1 and 3 months to assess long-term effects

3 months

2 visits (remote)

What Are the Treatments Tested in This Trial?

Interventions

• High Frequency Repetitive Transcranial Magnetic Stimulation (HF rTMS)
• Sham Repetitive Transcranial Magnetic Stimulation (sham- rTMS)

Trial Overview The study tests a new intervention combining emotion regulation strategies with brain stimulation (HF rTMS or sham-rTMS) over four sessions, aiming to reduce distress from misophonia by targeting the brain's emotion regulation areas.

How Is the Trial Designed?

Group I: Cognitive Restructuring + High Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Experimental Treatment 2 Interventions

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 II: Cognitive Restructuring + Shame Repetitive Transcranial Magnetic Stimulation (rTMS) Active Control 2 Interventions

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.

High Frequency Repetitive Transcranial Magnetic Stimulation (HF rTMS) is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

• Depression
• Obsessive Compulsive Disorder
• Smoking

Approved in European Union as rTMS for:

• Depression
• Obsessive Compulsive Disorder

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Misophonia Research Fund

Collaborator

Trials

2

Recruited

120+

Misophonia Research Fund

Collaborator

Trials

2

Recruited

120+

Published Research Related to This Trial

In a study involving 13 patients with chronic tinnitus who did not respond to conventional treatments, prolonged low-frequency rTMS (1 Hz) was effective in reducing symptoms for 62.5% of participants, with effects lasting about 5 days after treatment.

High-frequency rTMS (10 Hz) was found to be ineffective, suggesting that the frequency and duration of stimulation are critical factors in the potential treatment of tinnitus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Magnetic stimulation of the auditory cortex for disabling tinnitus: preliminary results]. Londero, A., Lefaucheur, JP., Malinvaud, D., et al.[2019]

In a study involving 19 patients with chronic tinnitus, dual-site repetitive transcranial magnetic stimulation (rTMS) targeting both the auditory cortex and dorsolateral prefrontal cortex significantly improved tinnitus severity compared to single-site rTMS targeting only the dorsolateral prefrontal cortex.

Patients receiving dual-site rTMS also showed greater improvements in anxiety and sleep quality, suggesting that targeting both auditory and non-auditory brain areas may enhance treatment outcomes for tinnitus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Treatment Outcomes Following Either Prefrontal Cortical-only or Dual-site Repetitive Transcranial Magnetic Stimulation in Chronic Tinnitus Patients: A Double-blind Randomized Study. Noh, TS., Kyong, JS., Chang, MY., et al.[2022]

A 62-year-old man with persistent tinnitus and depression showed significant improvement after receiving low-frequency rTMS targeting both the right dorsolateral prefrontal cortex and the left auditory cortex.

This case suggests that sequential stimulation of multiple brain regions using rTMS may be an effective treatment approach for patients suffering from tinnitus and associated depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case Report: Low-Frequency Repetitive Transcranial Magnetic Stimulation to Dorsolateral Prefrontal Cortex and Auditory Cortex in a Patient With Tinnitus and Depression. Chang, CH., Wang, WL., Shieh, YH., et al.[2022]

A systematic review of 106 studies involving 1815 patients showed that repetitive transcranial magnetic stimulation (rTMS) is generally safe, with mild adverse events occurring in 16.7% of subjects.

The most serious adverse event was seizure, with a very low risk of 0.16%, while aggravation of sensory phenomena occurred in 1.54% of cases, indicating that while rTMS is well-tolerated, further research is needed to systematically assess safety risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of repetitive transcranial magnetic stimulation in patients with pathologic positive sensory phenomena: a review of literature. Muller, PA., Pascual-Leone, A., Rotenberg, A.[2021]

Repetitive magnetic stimulation (rTMS) is a non-invasive and painless technique that can effectively activate specific areas of the brain, making it useful for studying language, memory, and visual perception.

rTMS shows potential therapeutic benefits for conditions like movement disorders and depression, but there are safety considerations regarding its potential to induce seizures, which are addressed in the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Repetitive transcranial magnetic stimulation. Possibilities, limits and safety aspects]. Brandt, SA., Ploner, CJ., Meyer, BU.[2019]

High-frequency repetitive transcranial magnetic stimulation (rTMS) applied to the primary motor cortex is definitively effective for pain relief, while high-frequency rTMS targeting the left dorsolateral prefrontal cortex is effective for treating depression, based on a review of evidence up to March 2014.

Low-frequency rTMS of the right dorsolateral prefrontal cortex shows probable efficacy for depression, and high-frequency rTMS of the left dorsolateral prefrontal cortex may help with negative symptoms of schizophrenia, indicating that rTMS can be a valuable treatment option for various mental health conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Lefaucheur, JP., André-Obadia, N., Antal, A., et al.[2022]

In a phase 1 clinical trial involving 10 children with Tourette syndrome, low-frequency repetitive transcranial magnetic stimulation (rTMS) to the supplementary motor area significantly reduced tic severity, as indicated by a decrease in the Yale Global Tic Severity Scale score (p<0.001).

The rTMS treatment was well-tolerated by all participants, demonstrating that this method is feasible and safe for use in children with Tourette syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral transcranial magnetic stimulation of the supplementary motor area in children with Tourette syndrome. Kahl, CK., Kirton, A., Pringsheim, T., et al.[2021]

In a case study involving a single patient, maintenance sessions of low-frequency repetitive transcranial magnetic stimulation (1 Hz rTMS) successfully reduced tinnitus loudness to a visual analogue rating (VAR) of 6 or lower, demonstrating its feasibility for managing chronic tinnitus.

The treatment was well tolerated with no side effects, and tinnitus remained unobtrusive in daily life for four months after the final maintenance session, suggesting potential long-term benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance repetitive transcranial magnetic stimulation can inhibit the return of tinnitus. Mennemeier, M., Chelette, KC., Myhill, J., et al.[2021]

A study involving 24 normal-hearing subjects found that while repetitive transcranial magnetic stimulation (rTMS) did not significantly affect hearing thresholds, it did cause a temporary decrease in otoacoustic emissions (TEOAEs) for those with less ear protection, indicating a minor alteration in hearing function.

The transient nature of the hearing disturbance suggests that even with proper safety measures, rTMS noise can impact hearing mechanisms, which is an important consideration for safety guidelines, especially at higher stimulation intensities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation: hearing safety considerations. Tringali, S., Perrot, X., Collet, L., et al.[2018]

A 51-year-old male with treatment-resistant tinnitus experienced significant and lasting relief after 20 sessions of bilateral 10 Hz rTMS targeting the dorsomedial prefrontal cortex, showing a 24-point drop in tinnitus handicap and a reduction in loudness from 15 dB to 1 dB.

This case is the first to report the use of rTMS on the DMPFC for tinnitus, suggesting that this method could be a promising new treatment strategy worth further research, especially since current treatments often provide only moderate or temporary relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral Dorsomedial Prefrontal Cortex rTMS for Tinnitus Treatment: A Successful Case. Ciminelli, P., Sender, D., Palmeira, M., et al.[2020]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032724001368

An experimental examination of neurostimulation and ... Excitatory rTMS also enhanced the regulation of emotions associated with misophonic sounds in both groups when measured by SUDS (dcontrol = 1.28 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3085788/

Cognitive effects of high-frequency repetitive transcranial ... To summarize the results, we can state that high-frequency rTMS (10–20 Hz) is most likely to cause significant cognitive improvement when applied over the left ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06333925

Study Details | NCT06333925 | Using Neurostimulation to ... 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 ...

4. withpower.com withpower.com/trial/phase-misophonia-4-2025-eecf1

Transcranial Magnetic Stimulation for Misophonia The expert consensus indicates that repetitive TMS (rTMS) is effective for treating chronic neuropathic pain, major depressive episodes, and auditory ...

5. medrxiv.org medrxiv.org/content/10.1101/2023.06.25.23291872v1.full.pdf

Identifying Optimal Parameters for Neuroscience-Informed ... A systematic literature review of the clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) in non-treatment resistant ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9359080/

The neurobiology of misophonia and implications for novel ... Emerging research findings suggest that misophonia may have a unique neural signature. Specifically, when examining responses to misophonic trigger sounds, ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04348591

NCT04348591 | Identifying the Optimal Neural Target for ... Misophonia, the inability to tolerate certain repetitive aversive sounds that are common, is gaining recognition as a debilitating condition ...