Anxiety Disorder Clinical Trial
— MISO-STIMOfficial title:
Using Neurostimulation to Accelerate Change in Misophonia: a Pilot Study
Misophonia, the inability to tolerate certain repetitive distressing sounds that are common, is gaining, recognition as an impairing condition. It is not a well-understood condition and there are no known treatments. The purpose of this study is to test a new misophonia intervention that uses emotion regulation strategies and different types of brain stimulation on misophonic distress. This study will examine changes in brain activity during presentation and regulation of misophonic versus distressing sounds. The study team plans to alter activity in a key area of the brain responsible for emotion regulation circuitry over 4 sessions with the goal to test if this intervention helps misophonic distress. Sixty adult participants with moderate to severe misophonia will be recruited and taught an emotion regulation skill and randomly assigned to receive one of two types of repetitive transcranial magnetic stimulation (rTMS). The study includes 9-10 visits: the remote screening visit(s), the initial MRI, the four neurostimulation sessions, the follow-up MRI, and two additional remote 1- and 3-month follow-up visits.
Status | Recruiting |
Enrollment | 60 |
Est. completion date | November 30, 2026 |
Est. primary completion date | November 30, 2026 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 55 Years |
Eligibility | Inclusion Criteria: - 18-55 - verbal agreement to maintain dose of prescribed psychotropic medication (if any) and/or psychotherapy (if any) constant throughout the study, provided they are stable on it for the past 4 weeks (except exclusion medication and except if there is a medical emergency requiring changes in medication). - DMQ Impairment score >= 14 Exclusion Criteria: - current or past history of mania or psychosis; current hypomania - verbal IQ< 90 as per the NART - not medically cleared for TMS or fMRI (such as taking medications known to reduce the seizure threshold such as Lithium, Clozaril, stimulants including the ADHD medications (e.g. Ritalin, Adderall), Wellbutrin/Buproprion, Provigil (Modafinil), Aminophylline, and Theophylline) - DMQ Impairment score < 14 - younger than 18 and older than 55 - pregnant - high risk for suicide (defined as having attempted suicide in past 6 months; suicide attempt within the past 10 years with current ideation with plan or preferred method available) - moderate/severe current alcohol or substance use disorder, or past severe alcohol use disorder - unable to read, blind, or deaf, or unwilling to give consent - cannot come to Duke for the in-person study visits - current uncontrolled anorexia or other condition requiring hospitalization - conditions associated with increased intracranial pressure, space occupying brain lesion, transient ischemic attack, cerebral aneurysm, dementia, Parkinson's or Huntington's disease, multiple sclerosis - use of investigational drug or devices within 4 weeks of screening - started/changed psychotropic medications or started psychotherapy in the prior 4 weeks, or plans to change medication or stop psychotherapy during the study |
Country | Name | City | State |
---|---|---|---|
United States | Duke University Medical Center | Durham | North Carolina |
Lead Sponsor | Collaborator |
---|---|
Duke University | Misophonia Research Fund |
United States,
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* Note: There are 16 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Changes in self-reported cognitive flexibility | Change in self-reported cognitive flexibility as measured by the Cognitive Control and Flexibility Questionnaire (CCFQ), will be examined using difference from baseline on these assessments and scores one week and 1-and-3 month follow-up after training. The CCFQ has 18 items, rated from "1" strongly disagree to "7" strongly agree, with higher scores indicating more flexibility. | Baseline, 1 week follow-up after neurostimulation, 1- and 3-month follow-up | |
Other | Baseline emotional dysregulation | Baseline Difficulties with Emotion Regulation (DERS) will be used as a moderator of outcomes. DERS has Min-Max score ranges from 36-180 (with higher scores signifying more difficulties with emotion regulation. | Baseline | |
Other | Baseline hyperacusis | Baseline Hyperacusis scores will be used as a moderator of outcomes. The multidimensional inventory of sound tolerance in adults (MIST-A) is a 25-item measure that includes relevant hyperacusis questions ranging from answers to never (not in the past month) to very often (multiple times per day). The higher the score on the hyperacusis items, the more likely the participant has hyperacusis, separate from misophonia. | Baseline | |
Other | Baseline Affect Intensity | Baseline Affect Intensity Measure (AIM) will be used as a moderator of outcomes. The AIM is a 40 item instrument with items being rated from "1" never to "6" always. Higher scores indicate higher affective intensity in emotional situations. | Baseline | |
Other | Change in Emotional distress | The Affect Sensitivity Index (ASI) will be collected to capture emotional distress and to explore changes in this area in this sample after the intervention. ASI is a 16 item scale containing items specifying different concerns someone could have regarding their distress/anxiety. Scores range from 0 to 64 with higher scores meaning higher levels of distress. | Baseline, 1 week follow-up after neurostimulation, 1- and 3-month follow-up | |
Other | Change in self-reported Emotion regulation | a modified version of the PROMIS-self efficacy in emotion regulation scale (PROMIS-SEME) will be collected to capture emotion regulation and to explore changes in these areas in this sample after the intervention. The modified PROMIS-SEME is 16 items on a rating of 1 "I am not all confident" to 5 "I am very confident" with a score ranging from 16 to 80. Higher scores indicate higher ability to regulate emotions. | Baseline, 1 week follow-up after neurostimulation, 1- and 3-month follow-up | |
Other | Change in Sensory sensitivity | The Glasgow Sensory Questionnaire (GSQ) will be collected to capture sensory differences and to explore changes in these areas in this sample after the intervention. The GSQ scale is a 42 item measure which captures self-rated hyper- and hypo-sensory sensitivity to stimuli across seven sensory domains. Responses are coded on a scale from 0 to 4 and total scores can range from 0 to 168 points. The higher scores mean more sensory sensitivity. | Baseline, 1 week follow-up after neurostimulation, 1- and 3-month follow-up | |
Other | Change in Interoceptive Awareness | the Multidimensional Assessment of Interoceptive Awareness version 2 (MAIA-2) will be collected to capture change in interoceptive awareness and to explore changes in these areas in this sample after the intervention. MAIA-2 is a 37 item measure; an 8-subscale state-trait self-report questionnaire to measure 5 dimensions of interoception (awareness of bodily sensations). Scores are between 0 and 5, where higher score equates to more awareness of bodily sensation. A percentile is also calculated, indicating how the responded scored in comparison to a normative sample. The results from the MAIA-2 focus upon the individual scale scores as a total score is not meaningful | Baseline, 1 week follow-up after neurostimulation, 1- and 3-month follow-up | |
Primary | Number of clusters across the whole brain with significant BOLD changes between conditions contrasting follow up with intake, and exposure to misophonic versus aversive sounds | Blood Oxygenation Level Dependent (BOLD) imaging is a technique that is commonly used for estimating brain activity using functional magnetic resonance imaging (fMRI). Change in the fMRI BOLD signal notes changes in brain blood flow and blood oxygenation, which are associated with neuronal activity. For each participant,the difference in BOLD activation between follow up and intake was computed. The BOLD signal contrast between engaging with misophonic sounds and engaging with aversive sounds were compared between conditions across the whole brain on a voxel-wise basis. Voxel-wise significant results (i.e., z > 2.3) were clustered to statistically correct for multiple comparisons. The number of significant clusters that emerged from this analysis in each condition are presented as outcome. | during the neuroimaging session, within 2 months of the intake assessment | |
Primary | Number of clusters across the whole brain with significant BOLD changes between conditions contrasting follow up with intake, and downregulation of versus exposure to misophonic sounds | Blood Oxygenation Level Dependent (BOLD) imaging is a technique that is commonly used for estimating brain activity using functional magnetic resonance imaging (fMRI). Change in the fMRI BOLD signal notes changes in brain blood flow and blood oxygenation, which are associated with neuronal activity. For each participant, the difference in BOLD activation between follow up and intake was computed. The BOLD signal contrast between downregulating and engaging with misophonic sounds were compared between conditions across the whole brain on a voxel-wise basis. Voxel-wise significant results (i.e., z > 2.3) were clustered to statistically correct for multiple comparisons. The number of significant clusters that emerged from this analysis in each condition are presented as outcome. | during the neuroimaging session, within 2 months of the intake assessment | |
Primary | Differential change in BOLD signal within the Anterior Insular Cortex (AIC) activation when being presented with misophonic versus non-misophonic but aversive sounds | Blood Oxygenation Level Dependent (BOLD) imaging is a technique that is commonly used for estimating brain activity using functional magnetic resonance imaging (fMRI). Change in the fMRI BOLD signal notes changes in brain blood flow and blood oxygenation, which are associated with neuronal activity. For each participant, change in activation during the presentation of misophonic versus aversive sounds from baseline to follow up will be computed. An anterior insular cortex (AIC) mask will be employed to find the maximum value of the [hear misophonic sounds > hear aversive sounds] contrast in this region. Once the voxel containing this maximum will beidentified, a sphere ROI will be created around this spot (restricted to the AIC mask) and the average contrast value within this sphere will be used as the outcome variable. A larger score indicates more activity when hearing misophonic versus aversive sounds. | during the neuroimaging session, within 2 months of the intake assessment | |
Primary | Differential change in BOLD signal connectivity between the left Anterior Insular Cortex (AIC) and the right dorsolateral prefrontal cortex (dlPFC) when downregulating versus experiencing distress related to misophonic trigger sounds | Blood Oxygenation Level Dependent (BOLD) imaging is a technique that is commonly used for estimating brain activity using functional magnetic resonance imaging (fMRI). For each participant, change in activation during the [downregulate vs. listen to misophonic sounds] contrast from baseline to follow up will be computed. A left anterior insular cortex (AIC) mask will be employed to find the maximum value for the contrast of interest in this region. A psychophysiological interaction (PPI) analysis will be conducted, to identify the voxel within the right dlPFC with the highest positive correlation with the max activation AIC voxel. A sphere ROI will be created around this right dlPFC spot (restricted with a dlPFC mask) and the average contrast value within this sphere will be used as the outcome connectivity variable. A larger score indicates more connectivity when downregulating versus hearing misophonic sounds. | during the neuroimaging session, within 2 months of the intake assessment | |
Primary | Change in misophonia impairment and severity using a composite | Change in misophonia impairment and severity will be investigated by using a composite score that will be created from the following scales and interview to examine changes in misophonia impairment and severity: the Duke Misophonia Questionnaire (DMQ), the Duke Misophonia Interview (DMI), the Duke-Vanderbilt Misophonia Screening Questionnaire (DVMSQ). A higher score on the DMQ impairment indicates more impairment (ranges 0-48). Similarly, higher scores on the DVMSQ and DMI indicate higher levels of impairment and distress. These measures are collected at all possible time points, depending on the range of time that they cover (e.g., DMI is not collected at 1 week follow up because it asks for impairment in the past month). | Baseline, 1 week follow-up after neurostimulation, 1- and 3-month follow-up | |
Primary | Skin conductance level (scl) | Physiological arousal measured by SCL during each neurostimulation visit will be extracted using Acqknowledge software and BIOPAC hardware. Raw galvanic skin response will be continuously collected throughout the experiment. Raw data will then be examined for abrupt changes (skin conductance responses), which will be removed. The processed data will then be averaged for each experimental block. Higher SCL means higher arousal. | Baseline, and two minute blocks during the 4 neurostimulation sessions (when participants downregulate emotions associated with misophonic triggers) | |
Primary | Change in Subjective Unites of Distress (SUDS) | Self reported distress after each sound presentation will also be examined for differences when accounting for baseline distress (during the neurostimulation sessions). SUDS will be measured using a 0-9 sale, where 0 indicates no distress, and 9 indicates extreme distress. The outcome measure represents SUDS after misophonic sound presentations minus SUDS after baseline. Higher SUDS represents higher distress. | Baseline, during the experimental blocks of the neurostimulation sessions (which will occur over 4 days within a month of the initial assessment) | |
Secondary | Changes in self-reported psychopathology | Change in self-reported psychopathology as measured by the OQ-45 will be examined one week, one month and three months after the intervention when compared to baseline. The Outcome Questionnaire-45 (OQ-45) is a 45-item self-report measure used to track severity of psychopathology throughout treatment. It consists of subscales that identify three types of problems that lead to general stress: psychological symptoms, interpersonal conflicts, and problems with social roles. Items are rated on a Likert scale ranging from 0 (never) to 4 (almost always). Scores range from 0 to 180. Higher scores indicate higher psychopathological distress than lower scores. | Baseline, 1 week follow-up after neurostimulation, 1- and 3-month follow-up | |
Secondary | Changes in clinician-assessed psychopathology | The Quick structural clinical interview for DSM-5 disorders (Quick-SCID) will be administered to examine changes in clinician-rated psychopathology. This clinician administered interview will be done at baseline and then again at the 1 and 3 month follow-up timepoints to assess for any change compared to baseline. | Baseline, 1 week follow-up after neurostimulation, 1- and 3-month follow-up | |
Secondary | Emotional dysregulation as measured by the Difficulties in Emotion Regulation Scale (DERS) | DERS will examine changes in emotional dysregulation between conditions after the intervention. The DERS has Min-Max score ranges from 36-180 (with higher scores signifying more difficulties with emotion regulation). | Baseline, 1 week follow-up after neurostimulation, 1- and 3-month follow-up |
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