Behavioral and Pharmacological Reconsolidation Interference in Misophonia

NCT05928689 | Completed Early Phase 1 FDA Drug

• 1 other identifier: STUDY-22-01280
• Study Type: interventional
• Target: 141
• Locations: 1 country
• Sites: 1

Brief Summary

One of the core processes presumably underlying misophonia - a condition characterized by decreased tolerance for specific sounds - is associative learning. Using behavioral, computational, and neural analyses of emotional learning and memory processes to understand the unknown behavioral and neural mechanisms underlying misophonia's associative learning and memory, the study team will evaluate whether interference with the reconsolidation of a reactivated misophonia memory with propranolol can alleviate aversive reaction to misophonia-related cues.

Conditions

Misophonia

Outcome Measures

Primary Outcomes (3)

• Change in average Galvanic skin response based on deflections of a wave

  Using galvanic skin response based on deflections of a wave, a difference between the average response to the misophonia-related video before and after the pharmacological or behavioral manipulation will be measured. The difference in scores across conditions will be compared. A greater deflection indicates greater sympathetic nervous system arousal.

  Baseline and after 6 hours

• Change in average heart rate

  Using heart rate measurement, a difference between the average response to the misophonia-related video before and after the pharmacological or behavioral manipulation will be measured. The difference in scores across conditions will be compared. Reduced heart rate will indicate manipulation efficacy

  Baseline and after 6 hours

• Change in Approach-Avoidance test

  Using an approach-avoidance test, the difference between the monetary amounts earned before and after the pharmacological or behavioral manipulation will be measured. The minimum monetary amount earned is $0 and the maximum monetary amount earned is $23. A higher monetary amount earned indicates greater approach towards an avoidant cue. The difference in monetary amounts across conditions will be compared.

  Baseline and after 6 hours

Secondary Outcomes (9)

• Change in Approach-Avoidance test

  about 1 week later

• Change in Approach-Avoidance test

  Baseline and 1 month later

• Change in decision making task

  Baseline and after 6 hours

• Change in decision making task

  Baseline and about 1 week

• Change in decision making task

  Baseline and 1 month later

Study Arms (5)

Memory Reminder followed by Propranolol Hydrochloride

EXPERIMENTAL

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.

Drug: Propranolol Hydrochloride tablet; Behavioral: Reminder

Memory reminder followed by Placebo

PLACEBO COMPARATOR

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.

Behavioral: Reminder; Drug: Placebo

No memory reminder followed by Propranolol Hydrochloride

EXPERIMENTAL

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.

Drug: Propranolol Hydrochloride tablet

Memory reminder followed by counterconditioning

EXPERIMENTAL

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.

Behavioral: Reminder; Behavioral: Counterconditioning

No memory reminder followed by counterconditioning

EXPERIMENTAL

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.

Behavioral: Counterconditioning

Interventions

Propranolol Hydrochloride tablet DRUG

Single dose of 40 mg propranolol tablet

Memory Reminder followed by Propranolol Hydrochloride; No memory reminder followed by Propranolol Hydrochloride

Reminder BEHAVIORAL

Reactivation of misophonia trigger memory

Memory Reminder followed by Propranolol Hydrochloride; Memory reminder followed by Placebo; Memory reminder followed by counterconditioning

Counterconditioning BEHAVIORAL

Counterconditioning will consist of presentation of misophonia cues paired with monetary rewards.

Memory reminder followed by counterconditioning; No memory reminder followed by counterconditioning

Placebo DRUG

Matching placebo tablet

Memory reminder followed by Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Hypersensitive to presence of a specific sound, which may be accompanied by irritation, anger/outbursts, or fear.
• Must be between the ages of 18 - 55.
• Must be fluent in English since the study's instructions, surveys, and tasks will be in English

You may not qualify if:

• Disability or medical condition that prohibits completion of study. Participants must be able to complete all study procedures to ensure optimal conditions for data analysis.
• CNS disease, such as history of brain abnormalities (e.g., neoplasms, subarachnoid cysts), cerebrovascular disease, infectious disease (e.g., abscess), or other neurological disease, history of head trauma (defined as loss of consciousness\>3 min), or history of seizures without a resolved etiology. CNS disease and drugs that act in the peripheral or central nervous system are likely to have effects on patterns of neural activity. We wish to minimize confounding variables.
• Recently used drugs of abuse.
• Pregnancy. The risks associated with neither propranolol exposure during gestation have been studied extensively. We wish to safeguard the health of potential participants and their children.
• Lactation. Propranolol is excreted in human breast-milk, and its impact on infant development has not been studied. We wish to safeguard the health of potential participants and their children.
• Regular use of medication metabolized in the CYP2D6, 1A2, or 2C19 pathways. Drugs that are metabolized in the same pathway as propranolol may increase its efficacy or toxicity. We wish to safeguard the health of participants.
• Blood pressure over 150/100 or under 100/60 (applicable for either systolic or diastolic measures) and any hypertension requiring medication. Propranolol is known to pose additional risk to individuals with a number of medical conditions. We wish to safeguard the health of our participants.
• Pulse over 100 or under 55.
• History of cardiovascular illness such as cardiac arrhythmia, coronary heart disease or any cardiac dysfunction that requires medication.
• Active respiratory illness including bronchospastic pulmonary disease and chronic obstructive pulmonary disease
• Diabetes mellitus.
• Other medical conditions that make it unsafe to take propranolol (e. g. allergy to propranolol).

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

misophonia

Interventions

Propranolol

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Daniela Schiller, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• James Murrough, MD, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Laili Soleimani, MD, Msc

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: This study is multi-arm and single-site randomized study that is placebo-controlled and single- and double-blinded depending on the condition assignment. Some groups will experience reminders, or short exposures to misophonia-related cues. Some groups will take the study intervention, propranolol hydrochloride (or matching placebo) oral tablets, and some will undergo counterconditioning, by presenting the misophonia cues with monetary rewards (in a continuous reinforcement schedule with fixed monetary amounts).
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neuroscience and Psychiatry

Model Details: The study team will measure reactivity to misophonia-related cues following either a pharmacological manipulation via a 40 mg propranolol tablet or behavioral manipulation via counterconditioning. The study team predicts that participants with misophonia who experience a reminder (reactive a misophonia memory) and receive the pharmacological or behavioral manipulation, will show reduced reactivity to misophonia cues. Other groups that undergo one of these components alone (reminder only, drug only, counterconditioning only) will continue to show heightened reactivity to misophonia cues.

Study Record Dates

• First Submitted: June 21, 2023
• First Posted: July 3, 2023
• Study Start: June 2, 2023
• Primary Completion: September 30, 2024
• Study Completion: September 30, 2024
• Last Updated: October 16, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Time Frame: 2 months after publication
• Access Criteria: Open access with no restrictions

Locations

US (1)