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Identifying the Optimal Neural Target for Misophonia Interventions

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ClinicalTrials.gov Identifier: NCT04348591
Recruitment Status : Recruiting
First Posted : April 16, 2020
Last Update Posted : October 30, 2020
Sponsor:
Collaborator:
Misophonia Research Fund
Information provided by (Responsible Party):
Duke University

Brief Summary:

Misophonia, the inability to tolerate certain repetitive aversive sounds that are common, is gaining recognition as a debilitating condition. It is not a well-understood condition and there are no known treatments. Up to one in five people report moderate or higher misophonia symptoms; nevertheless, resources aimed at understanding and treating this problem are scarce. In order to align misophonia research with the priorities of large funding agencies such as the National Institute of Mental Health, the investigators propose a novel study aimed at separating misophonic distress from other types of emotional distress. The investigators plan to examine changes in brain activation during presentation and regulation of misophonic versus distressing sounds. Emergent neural networks that may be involved in misophonia will then be tested in the lab with the use of noninvasive neurostimulation, a novel tool that can enhance or inhibit activation in a targeted brain region. The investigators plan to modulate activation in key areas of the misophonia brain circuitry with the aim to identify the optimal neural target for misophonia interventions. Our multidisciplinary team at the Duke Center for Misophonia and Emotion Regulation brings together experts in misophonia, neuroscience, neuromodulation, neurology, and biostatistics who share the long-term goal of developing and refining an intervention for this condition in an environment that is optimal to conduct the proposed research.

The investigators propose to recruit adults who self-report significant misophonia symptoms and adults who meet criteria for a current psychiatric disorder and who self-report difficulties calming down when upset. All participants will undergo a brain imaging session during which misophonic cues; distressing, non-misophonic cues; or neutral cues will be presented. Participants will then be asked to experience, or attempt to downregulate emotions associated with these cues. Based on the imaging results, two personalized neurostimulation targets will be identified: (1) the region in the frontal cortex with the most activity during the downregulation of misophonic versus neutral sounds and (2) the prefrontal region with the strongest functional connectivity to the anterior insular cortex (AIC), a brain region previously identified to be critical for misophonic distress. Participants will receive real or sham neurostimulation over the prefrontal cortex and insula in a random order, while engaging in listening to versus downregulating misophonic, aversive, or neutral cues. The investigators plan to assess emotional dysregulation, psychopathology, and misophonia with a multi-method battery of measures during all three study appointments. Feasibility and acceptability will be examined qualitatively. The investigators will use results from this study to design larger trials and to seek federal funding with the ultimate goal of designing an effective misophonia intervention. If successful, our study can be the first step in a series of investigations that establish the unique targets for neural intervention for misophonia.


Condition or disease Intervention/treatment Phase
Misophonia Emotion Dysregulation Behavioral: Cognitive Restructuring Device: neurostimulation Not Applicable

Detailed Description:
Consistent with NIMH strategic priorities, neural targets that account for individual differences are needed for the next generation of mental health interventions. Misophonia, the inability to tolerate certain aversive repetitive and common sounds, is gaining rapid recognition as a debilitating condition that is not currently well understood and for which interventions do not yet exist. In order to align research efforts to understand and treat misophonia with NIMH priorities, the investigators propose to conduct an experimental study that differentiates the neural circuitry of misophonia-induced distress from other types of emotional distress, and that begins to identify the optimal neural target for possible interventions. Noninvasive neurostimulation (i.e., the purposeful modulation of neural circuitry), such as repetitive transcranial magnetic stimulation (rTMS), is a powerful tool which can modulate neuronal activation and can be used to examine the responsiveness of neural circuits to intervention. Therefore, for this project, the investigators bring together a multidisciplinary team of researchers with expertise in misophonia, neuroscience, neuromodulation, biostatistics, and neurology with the aims to: (1) differentiate the brain circuitry dysfunction in misophonia compared to non-misophonia emotional distress and (2) identify the optimal intervention target for changing misophonic distress using rTMS. The investigators propose to recruit adults who self-report significant misophonia symptoms and a comparison group of adults who meet criteria for a current psychiatric disorder and who self-report high emotional dysregulation. Those who have contra-indications for MRI or rTMS will be excluded. All participants will undergo an MRI session during which misophonic cues; aversive, non-misophonic cues; or neutral cues will be presented. Participants will be asked to listen only or listen and attempt to downregulate emotions associated with these cues. Functional MRI (fMRI) analysis will then be performed to define two personalized neurostimulation targets defined as the region in the frontal cortex that is the most (1) activated during emotion regulation and (2) connected to the anterior insular cortex (AIC) during emotional experiencing. Participants will be assigned to receive active or sham neurostimulation over target 1 and target 2 in a random order, while engaged in listening to versus downregulating misophonic, aversive, or neutral cues. The investigators plan to employ excitatory neuromodulation to examine the effects of enhancing prefrontal cortex activation during emotion regulation. The investigators also plan to employ inhibitory neuromodulation to examine the effects of inhibiting AIC activation during listening only without efforts to regulate emotional distress. The investigators plan to assess emotional dysregulation, psychopathology, and misophonia with a multi-method battery of measures during all three study appointments. Feasibility and acceptability will be examined qualitatively. The investigators will use results from this study to design larger trials and to seek federal funding with the ultimate goal of designing an effective misophonia intervention. If successful, our study can be the first step in a series of investigations that establish the unique targets for neural intervention for misophonia.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The investigators plan to compare adults who report misophonia with adults who report clinical emotional dysregulation in their neurobiological response to misophonic, aversive, and neutral sounds
Masking: Double (Participant, Investigator)
Masking Description: All participants will undergo different types of neurostimulation to probe different areas of the emotion regulation and misophonic networks while being exposed to sounds. One of these neurostimulation blocks will involve sham (inactive) neurostimulation. The investigator and the participants will be blind to which block has active and which block has sham neurostimulation
Primary Purpose: Basic Science
Official Title: Identifying the Optimal Neural Target for Misophonia Interventions
Actual Study Start Date : October 28, 2020
Estimated Primary Completion Date : May 1, 2022
Estimated Study Completion Date : May 1, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Misophonia Group
Participants who endorse Misophonia will undergo a neuroimaging session to identify different neurostimulation targets. Then Misophonic participants will be exposed to aversive and neutral sounds while receiving real or sham neurostimulation over different pre-established neural targets.
Behavioral: Cognitive Restructuring
All participants will learn how to change their thinking in order to be less upset when confronted with stressors

Device: neurostimulation
all participants will receive inhibitory, excitatory, and sham transcranial magnetic stimulation over different neural targets during the experimental session. The purpose of the neurostimulation is not treatment, but causal interference/enhancing of brain circuitry to identify candidate neural regions for future interventions
Other Name: transcranial magnetic stimulation

Active Comparator: Emotional Dysregulation Clinical Group
Participants who self report high emotional dysregulation and who meet diagnostic criteria for a DSM disorder will undergo a neuroimaging session to identify different neurostimulation targets. Then these participants will be exposed to aversive and neutral sounds while receiving real or sham neurostimulation over different pre-established neural targets.
Behavioral: Cognitive Restructuring
All participants will learn how to change their thinking in order to be less upset when confronted with stressors

Device: neurostimulation
all participants will receive inhibitory, excitatory, and sham transcranial magnetic stimulation over different neural targets during the experimental session. The purpose of the neurostimulation is not treatment, but causal interference/enhancing of brain circuitry to identify candidate neural regions for future interventions
Other Name: transcranial magnetic stimulation




Primary Outcome Measures :
  1. Physiological outcome: Change from resting baseline in High Frequency Heart Rate Variability (HF-HRV) recorded during experimental blocks [ Time Frame: during the experimental blocks during the neurostimulation session (which will occur within a month of the initial assessment) ]
    HF-HRV will be extracted from 10 minute blocks during which participants engage in a behavioral strategy and receive neurostimulation

  2. Physiological Outcome: Change from resting baseline in Galvanic Skin Response (GSR) recorded continuously during experimental blocks [ Time Frame: during the experimental blocks during the neurostimulation session (which will occur within a month of the initial assessment) ]
    physiological arousal during experimental blocks will also be extracted using Acqknowledge software and Biopac hardware) and compared between misophonic and control participants (during the neurostimulation session)

  3. Behavioral outcome: Acceptability of procedures as measured by the percent of participants who complete the experimental neurostimulation session [ Time Frame: at the end of the neurostimulation session (session 3 in the experiment), which will occur within a month of thie initial assessment ]
    The investigators will record how many participants quit before the neurostimulation session is complete as a marker of acceptability

  4. Neuroimaging outcome: differential change in BOLD signal from baseline within the dorsolateral prefrontal cortex (dlPFC), as defined by a pre-established anatomical mask, when engaging in the regulation of emotional versus misophonic distress [ Time Frame: during the neuroimaging session, within a month of the intake assessment ]
    A dlPFC mask will be employed to extract the maximum activation in this region during regulation of emotional versus misophonic distress during the neuroimaging session

  5. Neuroimaging outcome: differential change in BOLD signal from baseline within the ventromedial prefrontal cortex (vmPFC) when engaging in the regulation of emotional versus misophonic distress [ Time Frame: during the neuroimaging session, within a month of the intake assessment ]
    A vmPFC mask will be employed to extract the maximum activation in this region during regulation of emotional versus misophonic distress

  6. Neuroimaging outcome: differential change in BOLD signal from baseline within the Anterior Insular Cortex (AIC) activation when being presented with cues for emotional versus misophonic distress [ Time Frame: during the neuroimaging session, within a month of the intake assessment ]
    An AIC mask will be employed to extract the maximum activation in this region during regulation of emotional versus misophonic distress during the neuroimaging session


Secondary Outcome Measures :
  1. Subjective Units of Distress (SUDS) [ Time Frame: during the experimental blocks during the neurostimulation session (which will occur within a month of the initial assessment) ]
    Self reported distress after experimental blocks will also be examined for differences when accounting for baseline distress (during the neurostimulation session). SUDS will be measured using a 0-9 sale, where 0 indicates no distress, and 9 indicates extreme distress

  2. Emotional dysregulation as measured by the Difficulties in Emotion Regulation Scale (DERS) [ Time Frame: throughout study completion, an average of 4 weeks. ]
    a self report assessing difficulties regulating emotions will be examined before and after the experiment (i.e., at the end of the neurostimulation session). The DERS ranges from 36 to 180, with higher scores indicating more dysregulation.

  3. Self-reported health status as measured by the Patient Reported Outcome Measurement information System (PROMIS)-43 Adult Profile [ Time Frame: throughout study completion, an average of 4 weeks. ]
    The PROMIS-43 is a 43-item questionnaire assessing health status in seven domains: physical function, anxiety, depression, fatigue, sleep disturbance, pain interference, and participation in social roles. lower scores indicate less impairment in functioning when compared to higher scores

  4. Changes in BOLD signal from active baseline across the whole brain during the presentation of aversive, non-misophonic sounds [ Time Frame: during the neuroimaging session, within a month of the intake assessment ]
    neural activation across the brain when engaging with aversive sounds versus neutral sounds during the neuroimaging day

  5. Changes in BOLD signal from active baseline across the whole brain during the presentation of misophonic sounds [ Time Frame: during the neuroimaging session, within a month of the intake assessment ]
    neural activation across the brain when engaging with misophonic sounds versus neutral sounds during the neuroimaging day

  6. Changes in BOLD signal from active baseline across the whole brain during the regulation of misophonic sounds [ Time Frame: during the neuroimaging session, within a month of the intake assessment ]
    neural activation across the brain when regulating versus experiencing misophonic sounds

  7. Changes in BOLD signal from active baseline across the whole brain during the regulation of aversive, non-misophonic sounds [ Time Frame: neuroimaging day ]
    neural activation across the brain when regulating versus experiencing misophonic sounds



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Interested participants will be excluded if:

  1. current or past history of mania or psychosis,
  2. verbal IQ < 70,
  3. not medically cleared for TMS or fMRI (for example taking medications known to reduce the seizure threshold such as Lamictal, Lithium, Clozaril, stimulants including the ADHD medications (e.g. Ritalin, Adderall), Wellbutrin/Buproprion, Provigil (Modafinil), Aminophylline, and Theophylline, implants, TBI, stroke, etc),
  4. going to jail in the next 2 months,
  5. pregnant,
  6. high risk for suicide
  7. moderate/severe current alcohol or substance dependence,
  8. cannot come to Duke for the three study visits.

Inclusion criteria are:

  1. stable psychotherapy and medication for at least 4 weeks
  2. self reports high emotional dysregulation OR misophonia

Participants will be matched on gender and age between the two groups


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04348591


Contacts
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Contact: Lisalynn D Kelley 9196846701 lisalynn.kelley@duke.edu
Contact: Andrada D Neacsiu 2063064531 andrada.neacsiu@duke.edu

Locations
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United States, North Carolina
Duke University Medical Center-Civitan Bldg Recruiting
Durham, North Carolina, United States, 27710
Contact: Andrada D Neacsiu, PhD    919-684-6714    andrada.neacsiu@duke.edu   
Contact: Lisalynn D Kelley, BA, CCRP    919-684-6701    lisalynn.kelley@duke.edu   
Principal Investigator: Andrada D Neacsiu, PhD         
Sub-Investigator: Mark Z Rosenthal, PhD         
Sub-Investigator: Kevin S LaBar, PhD         
Sub-Investigator: Lawrence Appelbaum, PhD         
Sub-Investigator: Noreen Bukhari-Parlakturk, MD PhD         
Sponsors and Collaborators
Duke University
Misophonia Research Fund
Investigators
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Principal Investigator: Andrada D Neacsiu Duke University Health System
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Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT04348591    
Other Study ID Numbers: Pro00103863
First Posted: April 16, 2020    Key Record Dates
Last Update Posted: October 30, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: I plan to share aggregated data but not individual participant data at this point.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Keywords provided by Duke University:
neurostimulation
neuroscience
misophonia
emotion dysregulation
insula