Behavioral and Pharmacological Reconsolidation Interference in Misophonia (Miso Prop)

• ClinicalTrials.gov Identifier: NCT05928689
• Recruitment Status: Recruiting
• First Posted: July 3, 2023
• Last Update Posted: December 12, 2023
• Sponsor: Icahn School of Medicine at Mount Sinai
• Information provided by (Responsible Party): Daniela Schiller, Icahn School of Medicine at Mount Sinai

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Misophonia	Drug: Propranolol Hydrochloride tablet; Behavioral: Reminder; Behavioral: Counterconditioning; Drug: Placebo	Early Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment

Intervention 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 (Participant, Care Provider, Investigator)
• Masking Description: 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).
• Primary Purpose: Other
• Official Title: Misophonia-Related Memory Modification Using Reconsolidation Mechanisms: Pharmacological and Behavioral Manipulation
• Actual Study Start Date: June 2, 2023
• Estimated Primary Completion Date: August 2024
• Estimated Study Completion Date: August 2024

Arms and Interventions

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.	Behavioral: Reminder; Reactivation of misophonia trigger memory; Drug: Placebo; Matching placebo tablet
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.

Outcome Measures

Primary Outcome Measures :

1. Change in average Galvanic skin response based on deflections of a wave [ Time Frame: Baseline and after 6 hours ]
   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.
2. Change in average heart rate [ Time Frame: Baseline and after 6 hours ]
   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
3. Change in Approach-Avoidance test [ Time Frame: Baseline and after 6 hours ]
   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.

Secondary Outcome Measures :

1. Change in Approach-Avoidance test [ Time Frame: about 1 week later ]
   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.
2. Change in Approach-Avoidance test [ Time Frame: Baseline and 1 month later ]
   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.
3. Change in decision making task [ Time Frame: Baseline and after 6 hours ]

   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.

4. Change in decision making task [ Time Frame: Baseline and about 1 week ]

   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.

5. Change in decision making task [ Time Frame: Baseline and 1 month later ]

   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.

6. Change in Average Galvanic skin response based on deflections of a wave [ Time Frame: about 1 week later ]
   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.
7. Change in Average Galvanic skin response based on deflections of a wave [ Time Frame: about 1 month later ]
   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.
8. Change in average heart rate [ Time Frame: about 1 week later ]
   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
9. Change in average heart rate [ Time Frame: about 1 month later ]
   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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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).

Contacts and Locations

Contacts

Contact: Alissa Chen, BA; 781-467-6462; alissa.chen@mssm.edu

Locations

United States, New York

Icahn School of Medicine at Mount Sinai; Recruiting

New York, New York, United States, 10029

Contact: Alissa Chen, BA alissa.chen@mssm.edu

Sponsors and Collaborators

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

More Information

• Responsible Party: Daniela Schiller, Professor of Neuroscience and Psychiatry, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT05928689
• Other Study ID Numbers: STUDY-22-01280
• First Posted: July 3, 2023
• Last Update Posted: December 12, 2023
• Last Verified: December 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Time Frame: 2 months after publication
• Access Criteria: Open access with no restrictions

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Propranolol; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents