Behavioral and Pharmacological Reconsolidation Interference in Misophonia

Study Overview
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Brief Summary
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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.

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

Conditions
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Misophonia

Intervention / Treatment
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* Drug: Propranolol Hydrochloride tablet
* Behavioral: Reminder
* Behavioral: Counterconditioning
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 |