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

Trial Summary

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 data supports the effectiveness of the treatment High Frequency Repetitive Transcranial Magnetic Stimulation (HF rTMS) for misophonia?

Research shows that repetitive transcranial magnetic stimulation (rTMS) has been effective in reducing symptoms for conditions like tinnitus and depression, suggesting it might help with misophonia too. For example, a study found that rTMS reduced tinnitus loudness and annoyance, and guidelines recognize its antidepressant effects, indicating potential benefits for other sensory-related conditions. ^{1 2 3 4 5}

Is repetitive transcranial magnetic stimulation (rTMS) generally safe for humans?

Repetitive transcranial magnetic stimulation (rTMS) is generally considered safe for humans, but it can produce loud sounds that may affect hearing if proper precautions are not taken. It is a non-invasive and painless method, though there are some concerns about potential epileptic effects, so safety guidelines and professional training are important. ^{1 3 6 7 8}

How does the treatment HF rTMS for misophonia differ from other treatments?

HF rTMS is a non-invasive treatment that uses magnetic fields to stimulate specific areas of the brain, which is different from traditional drug therapies. While there are no standard treatments for misophonia, HF rTMS has shown promise in treating other conditions like tinnitus by targeting brain regions involved in sensory processing, making it a novel approach for misophonia. ^{1 3 4 9 10}

What is the purpose of this trial?

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.

Research Team

Andrada D Neacsiu, PhD

Principal Investigator

Duke University

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Turkey pubmed.ncbi.nlm.nih.gov

Bilateral Dorsomedial Prefrontal Cortex rTMS for Tinnitus Treatment: A Successful Case. [2020]

2. United States 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. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Safety and tolerability of repetitive transcranial magnetic stimulation in patients with pathologic positive sensory phenomena: a review of literature. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Bilateral transcranial magnetic stimulation of the supplementary motor area in children with Tourette syndrome. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation: hearing safety considerations. [2018]

7. Germany pubmed.ncbi.nlm.nih.gov

[Repetitive transcranial magnetic stimulation. Possibilities, limits and safety aspects]. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Maintenance repetitive transcranial magnetic stimulation can inhibit the return of tinnitus. [2021]

9. France pubmed.ncbi.nlm.nih.gov

[Magnetic stimulation of the auditory cortex for disabling tinnitus: preliminary results]. [2019]

10. Switzerland 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. [2022]