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

141 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing whether propranolol can help people with misophonia, a condition where certain sounds cause strong negative reactions. The medication aims to weaken the bad memories associated with these sounds. By doing so, it might make these sounds less distressing for those affected. Propranolol has been used in various psychiatric treatments and has shown potential in reducing anxiety and improving cognitive functions.

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 propranolol safe for use in humans?

Propranolol, a medication used for various conditions, has been generally well-tolerated in humans, though it can cause side effects like dizziness, fatigue, and insomnia. It may also lead to serious reactions in some cases, such as resistance to epinephrine (a treatment for severe allergic reactions), so caution is advised, especially in patients with allergies. ^{1 2 3 4 5}

How does the drug propranolol differ from other treatments for misophonia?

Propranolol is unique for treating misophonia because it is a beta-blocker that can reduce both the emotional and physical reactions to trigger sounds and visuals, unlike other treatments that are largely unexplored for this condition. It works by calming the body's fight-or-flight response, allowing patients to experience less distress from their triggers. ^{2 4 5 6 7}

What data supports the effectiveness of the drug propranolol for treating misophonia?

A case study showed that propranolol, a beta-blocker, was effective in eliminating the emotional and physical symptoms of misophonia and misokinesia in a patient, allowing them to resume normal activities without distress. ^{2 5 7 8 9}

Who Is on the Research Team?

Daniela Schiller, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

James Murrough, MD, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Laili Soleimani, MD, Msc

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.

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

Pulse over 100 or under 55

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 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]

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]

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]

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]

Citations

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

A controlled study of alprazolam and propranolol in panic-disordered and agoraphobic outpatients. [2013]

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

Beta-blockers in the severely and profoundly mentally retarded. [2013]

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

Propranolol for the treatment of anxiety disorders: Systematic review and meta-analysis. [2022]

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

β-Blockers for the Treatment of Misophonia and Misokinesia. [2022]

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

The Safety and Effectiveness of High-Dose Propranolol as a Treatment for Challenging Behaviors in Individuals With Autism Spectrum Disorders. [2022]

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

Epinephrine-resistant anaphylaxis in a patient taking propranolol hydrochloride. [2013]

7. India pubmed.ncbi.nlm.nih.gov

Therapeutic class-specific signal detection of bradycardia associated with propranolol hydrochloride. [2021]

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

Propranolol in chronic anxiety disorders. A controlled study. [2022]

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

Propranolol for the control of disruptive behavior in senile dementia. [2019]