Behavioral + Propranolol for Misophonia

(Miso Prop Trial)

Overseen By Alissa Chen, BA

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Icahn School of Medicine at Mount Sinai

Must not be taking: CNS drugs, CYP2D6 drugs

Disqualifiers: CNS disease, Pregnancy, Hypertension, Diabetes, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 6 hours

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach for treating misophonia, a condition where certain sounds trigger intense reactions. The study tests propranolol, a medication, to determine if it can lessen these reactions by affecting how memories linked to these sounds are stored. Participants may receive propranolol or a placebo, along with reminders or behavioral techniques, to evaluate different strategies. The trial seeks individuals who are hypersensitive to specific sounds and experience irritation, anger, or fear as a result. Participants must not have certain medical conditions and should be able to follow study instructions in English. As an Early Phase 1 trial, this research focuses on understanding how propranolol works in people with misophonia, offering participants a chance to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

The trial requires that you do not regularly use medications that are metabolized in the CYP2D6, 1A2, or 2C19 pathways, as these can interact with propranolol. If you are on such medications, you may need to stop taking them to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that propranolol, a medication used in this trial, is usually well-tolerated. It has treated conditions like high blood pressure and migraines for many years. However, some people have reported side effects such as difficulty breathing and heart problems. These side effects are uncommon but can occur.

The counterconditioning approach, a behavioral technique, has shown promise in helping people with misophonia. This method has no known safety concerns because it doesn't involve medication; it uses mental exercises to change how the brain reacts to certain sounds.

Since this trial is in an early phase, the main goal is to assess the safety of these treatments for people with misophonia. Always consult a healthcare provider before joining a trial to ensure it's the right choice. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for misophonia because they explore unique approaches compared to current options, like cognitive behavioral therapy (CBT) or sound management strategies. Propranolol Hydrochloride, a beta-blocker commonly used for high blood pressure, is being tested to see if it can change the emotional response to misophonia triggers by altering memory reactivation. This approach is different because it targets the emotional intensity linked to misophonia sounds, potentially offering a quicker way to reduce symptoms. Additionally, the trial includes a behavioral arm using counterconditioning, which aims to retrain emotional responses to triggers, potentially providing an alternative to traditional therapies. These innovative methods could pave the way for more effective and faster relief for those affected by misophonia.

What evidence suggests that this trial's treatments could be effective for misophonia?

Research has shown that propranolol, a beta-blocker, can help reduce the emotional and physical reactions linked to misophonia. One case study demonstrated fewer symptoms with propranolol, as measured by a specific scale for misophonia. In this trial, some participants will receive propranolol, either with or without a memory reminder. Additionally, counterconditioning, a technique that changes responses to triggers, has shown promise in reducing misophonia symptoms by 70%. This method also helped reduce behaviors in families that might unintentionally worsen the condition. Other participants in this trial will undergo counterconditioning, with or without a memory reminder. Both treatments have shown potential in managing misophonia, but more research is needed to fully understand their effectiveness. ^{1 2 6 7 8}

Who Is on the Research Team?

Daniela Schiller, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Laili Soleimani, MD, Msc

Principal Investigator

Icahn School of Medicine at Mount Sinai

James Murrough, MD, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for adults aged 18-55 with misophonia, which means they have strong negative reactions to certain sounds. Participants must speak English fluently and not be pregnant, breastfeeding, or have a pulse outside of the range 55-100 bpm. They should not take specific medications that interact with propranolol, have high or low blood pressure issues, cardiovascular illnesses, respiratory diseases like COPD, diabetes mellitus, CNS diseases or recent drug abuse.

Inclusion Criteria

Hypersensitive to presence of a specific sound, which may be accompanied by irritation, anger/outbursts, or fear

Must be fluent in English since the study's instructions, surveys, and tasks will be in English

Exclusion Criteria

I am not pregnant, as the study involves risks to unborn children.

Pulse over 100 or under 55

My blood pressure is not between 100/60 and 150/100, or I need medication to manage it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo pharmacological or behavioral manipulation to interfere with the reconsolidation of misophonia-related memories

6 hours

1 visit (in-person)

Follow-up

Participants are monitored for changes in heart rate, approach-avoidance behavior, and galvanic skin response

1 month

What Are the Treatments Tested in This Trial?

Interventions

• Counterconditioning
• Placebo
• Propranolol Hydrochloride
• Reminder

Trial Overview

The study tests if interfering with memory reconsolidation using propranolol can reduce aversive reactions in misophonia when reminded of triggering sounds. It compares this approach against placebo and counterconditioning techniques through behavioral and neural analyses.

How Is the Trial Designed?

Group I: No memory reminder followed by counterconditioning Experimental Treatment 1 Intervention

This arm aims to have 30 participants with a behavioral manipulation. They will not receive a reminder to reactivate their memory of a misophonia trigger and then undergo counterconditioning.

Group II: No memory reminder followed by Propranolol Hydrochloride Experimental Treatment 1 Intervention

This arm aims to have 30 participants with a pharmacological manipulation. They will not receive a reminder to reactivate their memory of a misophonia sound and only receive a propranolol hydrochloride tablet.

Group III: Memory reminder followed by counterconditioning Experimental Treatment 2 Interventions

This arm aims to have 30 participants with a behavioral manipulation. They will receive a reminder to reactivate their memory of a misophonia trigger and then will undergo counterconditioning.

Group IV: Memory Reminder followed by Propranolol Hydrochloride Experimental Treatment 2 Interventions

This arm aims to have 30 participants with a pharmacological manipulation. They will receive a reminder to reactivate their memory of a misophonia trigger followed by ingestion of a propranolol hydrochloride tablet.

Group V: Memory reminder followed by Placebo Placebo Group 2 Interventions

This arm aims to have 30 participants with a pharmacological manipulation. They will receive a reminder to reactivate their memory of a misophonia trigger followed by ingestion of a placebo tablet.

Propranolol Hydrochloride is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Inderal for:

• Hypertension
• Angina pectoris
• Arrhythmias
• Migraine prophylaxis
• Performance anxiety

Approved in European Union as Inderal for:

• Hypertension
• Angina pectoris
• Arrhythmias
• Migraine prophylaxis
• Performance anxiety

Approved in Canada as Inderal for:

• Hypertension
• Angina pectoris
• Arrhythmias
• Migraine prophylaxis
• Performance anxiety

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Published Research Related to This Trial

In a double-blind crossover study involving 26 patients with chronic anxiety disorders, propranolol hydrochloride effectively reduced symptoms in 17 patients, indicating its potential as a treatment option.

While propranolol showed benefits in alleviating both physical and psychological symptoms of anxiety, the side effects were mostly mild and similar to anxiety symptoms, and its efficacy compared to other anti-anxiety medications remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propranolol in chronic anxiety disorders. A controlled study. Kathol, RG., Noyes, R., Slymen, DJ., et al.[2022]

The study analyzed data from the Canadian Adverse Drug Reaction Monitoring Program to assess the potential link between propranolol hydrochloride and bradycardia, finding that the signals for bradycardia were not statistically significant despite some high calculated statistics.

Although the results did not confirm a strong association between propranolol and bradycardia, the authors suggest that further investigation using larger databases is warranted due to the observed trends.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic class-specific signal detection of bradycardia associated with propranolol hydrochloride. Gavali, DK., Kulkarni, KS., Kumar, A., et al.[2021]

A systematic review of eight studies involving 302 participants found that propranolol did not show significant efficacy compared to placebo or benzodiazepines in treating anxiety disorders, including panic disorder and PTSD.

The evidence is currently insufficient to recommend propranolol as a routine treatment for anxiety disorders, as it did not demonstrate a clear benefit in alleviating symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Propranolol for the treatment of anxiety disorders: Systematic review and meta-analysis. Steenen, SA., van Wijk, AJ., van der Heijden, GJ., et al.[2022]

In a 6-week study involving 29 patients with agoraphobia and panic disorder, both propranolol and alprazolam were effective in reducing panic attacks and avoidance behavior.

Alprazolam showed a faster onset of its effects compared to propranolol, suggesting that while both medications work, propranolol may need further investigation to fully understand its potential benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A controlled study of alprazolam and propranolol in panic-disordered and agoraphobic outpatients. Ravaris, CL., Friedman, MJ., Hauri, PJ., et al.[2013]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10276561/

A systematic review of treatments for misophonia - PMC

This report showed a 70% reduction in misophonia symptoms. Family accommodation behaviors also significantly decreased, suggesting some added benefit to a ...

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S2451865423000510

Effectiveness of an innovative treatment protocol for ...

This trial is the first study worldwide testing the effectiveness of a combined CBT plus PMT protocol for misophonia in children and adolescents.

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8359510/

Cognitive behavioral therapy for misophonia: A randomized ...

The CBT group had an observed clinical improvement (CGI‐I < 3) in 37% compared to 0% in the waiting list group (p < .001). The effect of CBT was ...

4.

researchgate.net

researchgate.net/publication/276247465_Counterconditioning_Treatment_for_Misophonia

(PDF) Counterconditioning Treatment for Misophonia

These indicated large reductions in severity of misophonia and response to individual triggers, both at the end of treatment and at 10 months ...

5.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0165032716321681

Cognitive behavioral therapy is effective in misophonia

Following treatment 48% (N=42) of the patients showed a significant reduction of misophonia symptoms. Severity of misophonia and the presence of disgust were ...

6.

sciencedirect.com

sciencedirect.com/science/article/pii/S0165032725003982

A randomized controlled trial evaluating an mHealth ...

The present study aimed to evaluate the effectiveness of an mHealth app in reducing misophonia symptoms and related cognitions.

7.

frontiersin.org

frontiersin.org/journals/psychology/articles/10.3389/fpsyg.2025.1493676/full

Understanding the misophonic experience: a mixed ...

Our data showed that when experiencing “intrusion/violation,” the misophonia sufferer feels almost intentionally harmed.

8.

journals.lww.com

journals.lww.com/aips/fulltext/9900/quieting_the_triggers__exploring_therapeutic.139.aspx

Exploring Therapeutic Avenues for Misophonia

CBT is a widely practiced and evidence-based treatment for misophonia, aimed at helping individuals identify and alter unhelpful thought ...