Behavioral and Pharmacological Reconsolidation Interference in Misophonia (Miso Prop)

Misophonia-Related Memory Modification Using Reconsolidation Mechanisms: Pharmacological and Behavioral Manipulation

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.

Study Overview

• Status: Completed
• Conditions: Misophonia
• Intervention / Treatment: Drug: Placebo; Drug: Propranolol Hydrochloride tablet; Behavioral: Reminder; Behavioral: Counterconditioning

• Study Type: Interventional
• Enrollment (Actual): 141
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Memory Reminder followed by Propranolol Hydrochloride; 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; Single dose of 40 mg propranolol tablet; Behavioral: Reminder; Reactivation of misophonia trigger memory
Placebo Comparator: Memory reminder followed by Placebo; 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.	Drug: Placebo; Matching placebo tablet; Behavioral: Reminder; Reactivation of misophonia trigger memory
Experimental: No memory reminder followed by Propranolol Hydrochloride; 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; Single dose of 40 mg propranolol tablet
Experimental: Memory reminder followed by counterconditioning; 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; Reactivation of misophonia trigger memory; Behavioral: Counterconditioning; Counterconditioning will consist of presentation of misophonia cues paired with monetary rewards.
Experimental: No memory reminder followed by counterconditioning; 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; Counterconditioning will consist of presentation of misophonia cues paired with monetary rewards.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	about 1 week later
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 1 month later
Change in decision making task	Using a decision making task based on choice behavior (choosing the correct machine more often), the study team will fit computational models to understand reactivity to misophonia-related cues across conditions. The study team will measure a difference in the task responses after the pharmacological or behavioral manipulation. Measures will include learning rate, and a link between prediction error and self-reported mood. The scores across conditions will be compared.	Baseline and after 6 hours
Change in decision making task	Using a decision making task based on choice behavior (choosing the correct machine more often), the study team will fit computational models to understand reactivity to misophonia-related cues across conditions. The study team will measure a difference in the task responses after the pharmacological or behavioral manipulation. Measures will include learning rate, and a link between prediction error and self-reported mood. The scores across conditions will be compared.	Baseline and about 1 week
Change in decision making task	Using a decision making task based on choice behavior (choosing the correct machine more often), the study team will fit computational models to understand reactivity to misophonia-related cues across conditions. The study team will measure a difference in the task responses after the pharmacological or behavioral manipulation. Measures will include learning rate, and a link between prediction error and self-reported mood. The scores across conditions will be compared.	Baseline and 1 month later
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.	about 1 week later
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.	about 1 month later
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	about 1 week later
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	about 1 month later

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Investigators: Principal Investigator: 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

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2023
• Primary Completion (Actual): September 30, 2024
• Study Completion (Actual): September 30, 2024

Study Registration Dates

• First Submitted: June 21, 2023
• First Submitted That Met QC Criteria: June 23, 2023
• First Posted (Actual): July 3, 2023

Study Record Updates

• Last Update Posted (Actual): October 16, 2024
• Last Update Submitted That Met QC Criteria: October 15, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Propranolol
• Other Study ID Numbers: STUDY-22-01280

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The study team will publicly share analyzed statistical summaries which are sufficient for data assessment, reanalysis, and meta-analysis, and reproduction of figures.
• IPD Sharing Time Frame: 2 months after publication
• IPD Sharing Access Criteria: Open access with no restrictions

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No