Neurostimulation for Misophonia

(MISO-STIM Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Andrada D Neacsiu, PhD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Duke University

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

Disqualifiers: Mania, Psychosis, Substance use, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

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.

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.

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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.

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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.

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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

I am between 18 and 55 years old.

DMQ Impairment score >= 14

Trigger sounds include mouth/throat sounds

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

Trial 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)

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Duke University Medical Center Durham, NC

Who Is Running the Clinical Trial?

Duke University Lead Sponsor

Misophonia Research Fund Collaborator

Misophonia Research Fund Collaborator

References

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

Bilateral Dorsomedial Prefrontal Cortex rTMS for Tinnitus Treatment: A Successful Case. [2020] We present a successful tinnitus treatment case with intensity and distress reduction in a patient subjected to bilateral 10 Hz repetitive transcranial magnetic stimulation (rTMS) to the dorsomedial prefrontal cortex (DMPFC). Subjective tinnitus is the perception of sound in the ears or head when no corresponding external stimulus exists. Approximately 1%-2% of the population report severe tinnitus with daily life impairment. Sham-controlled studies have revealed benefits using rTMS in tinnitus, although the improvement is moderate or temporary, indicating the need for new strategies. Evidence that the DMPFC is important in tinnitus pathophysiology makes this area a promising target. A 51-year-old male patient with a 4-year history of treatment-resistant moderate bilateral tinnitus was treated with 20 sessions of bilateral 10 Hz DMPFC rTMS. The patient showed important reduction and sustained 4-month response in tinnitus loudness and annoyance, 24 point drop in tinnitus handicap inventory, visual analog scale reduction to zero, and tinnitus loudness of 1 dB compared to baseline 15 dB. Tinnitus treatment is challenging and new alternatives are needed. To our knowledge, this is the first report using rTMS to the DMPFC for tinnitus. In this protocol, important and sustained reduction of tinnitus annoyance and loudness was obtained. This outcome of the case suggests that this approach is promising for treating tinnitus and is worth further investigation.

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] We evaluated treatment outcomes following single-site repetitive transcranial magnetic stimulation (rTMS) in the dorsolateral prefrontal cortex (DLPFC) and dual-site rTMS in the auditory cortex (AC) and DLPFC (AC + FC).

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

Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). [2022] A group of European experts was commissioned to establish guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS) from evidence published up until March 2014, regarding pain, movement disorders, stroke, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, consciousness disorders, tinnitus, depression, anxiety disorders, obsessive-compulsive disorder, schizophrenia, craving/addiction, and conversion. Despite unavoidable inhomogeneities, there is a sufficient body of evidence to accept with level A (definite efficacy) the analgesic effect of high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the pain and the antidepressant effect of HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC). A Level B recommendation (probable efficacy) is proposed for the antidepressant effect of low-frequency (LF) rTMS of the right DLPFC, HF-rTMS of the left DLPFC for the negative symptoms of schizophrenia, and LF-rTMS of contralesional M1 in chronic motor stroke. The effects of rTMS in a number of indications reach level C (possible efficacy), including LF-rTMS of the left temporoparietal cortex in tinnitus and auditory hallucinations. It remains to determine how to optimize rTMS protocols and techniques to give them relevance in routine clinical practice. In addition, professionals carrying out rTMS protocols should undergo rigorous training to ensure the quality of the technical realization, guarantee the proper care of patients, and maximize the chances of success. Under these conditions, the therapeutic use of rTMS should be able to develop in the coming years.

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] Repetitive transcranial magnetic stimulation (rTMS) is emerging as a valuable therapeutic and diagnostic tool. rTMS appears particularly promising for disorders characterized by positive sensory phenomena that are attributable to alterations in sensory cortical excitability. Among these are tinnitus, auditory and visual hallucinations, and pain syndromes.

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

Bilateral transcranial magnetic stimulation of the supplementary motor area in children with Tourette syndrome. [2021] To explore the feasibility and possible effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) delivered to the supplementary motor area (SMA) on tic severity and motor system neurophysiology in children with Tourette syndrome.

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

Repetitive transcranial magnetic stimulation: hearing safety considerations. [2018] The guidelines for use of repetitive transcranial magnetic stimulation (rTMS) advise frequent updating of rTMS safety guidelines and recommendations. Although rTMS can produce sound of more than 120 dB C, which is sufficient to induce hearing loss, the effect of rTMS noise on the hearing of both patients and rTMS practitioners is understudied.

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

[Repetitive transcranial magnetic stimulation. Possibilities, limits and safety aspects]. [2019] Repetitive magnetic stimulation (rTMS) is a non-invasive, painless method to induce transient activation in circumscript regions of the human cortex. In contrast to TMS with single pulses rTMS allows a more effective stimulation of association cortex and temporary interference with the proper functioning of stimulated areas. Possible applications for examination of the functional anatomy of language lateralisation, memory functions and visual perception are discussed. Possible therapeutic for movement disorders and depression are discussed. On the basis of theoretical considerations and current experience rTMS induced epileptogenic effects are discussed and safety recommendations are given.

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

Maintenance repetitive transcranial magnetic stimulation can inhibit the return of tinnitus. [2021] A single patient was tested to examine the safety and feasibility of using maintenance sessions of low-frequency repetitive transcranial magnetic stimulation (1 Hz rTMS) to reduce tinnitus loudness and prevent its return over time.

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

[Magnetic stimulation of the auditory cortex for disabling tinnitus: preliminary results]. [2019] Tinnitus - the perception of sound in one or both ears or in the head when no external sound is present - can be disabling and is especially difficult to treat. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique for activating or inactivating specific areas of the cortex. The aim of this study was to assess the feasibility of magnetic neurostimulation of the primary and secondary auditory cortex in the treatment of disabling chronic tinnitus.

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] Repetitive transcranial magnetic stimulation (rTMS) has been widely used as a promising therapy for tinnitus. However, the exact target and stimulation sequence of rTMS that is most effective for treating tinnitus remains unclear. Here, we report a case of a 62-year-old man with treatment-refractory tinnitus and depression whose symptoms markedly improved after undergoing low-frequency rTMS over the right-side dorsolateral prefrontal cortex and left auditory cortex area. Our report indicates that low-frequency rTMS treatment that stimulates multiple brain regions sequentially is feasible and may clinically benefit patients with tinnitus and depression.