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This is an open label prospective pilot study of two neuromodulation interventions for patients suffering from dysphoria. Dysphoria is a transdiagnostic symptom of unease or dissatisfaction experienced across a range of diagnoses, including mood disorders and pain. There is a significant gap of treatment options across conditions with dysphoria, particularly non-medicated and self-care alternatives.
Many neuromodulation therapies require extensive medical resources or time to deliver. Thus, the investigators will test two non-invasive technologies administered in a manner that would reduce resources and/or time. Virtual Reality (VR) overlays the sensory system to block the external environment and provide vast range of meaningful sensory experiences. Transcranial Magnetic Stimulation (TMS) involves a magnetic pulse passing through the scalp to depolarize neurons in the outer cortex of the brain, and daily treatments over 6 weeks are currently FDA indicated for the treatment of major depressive disorder. Accelerated TMS is the delivery of treatment in a shorter period of time.
The primary objective of this study to demonstrate the preliminary effectiveness, tolerability, and feasibility of these two interventions: Guided Meditation VR for Wellness and Accelerated Transcranial Magnetic Stimulation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Guided Meditation VR for Wellness | Active Comparator | Selected modules of commercially available meditation VR |
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| Accelerated Transcranial Magnetic Stimulation: Treatment A | Active Comparator | Intermittent theta-burst over dlPFC |
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| Accelerated Transcranial Magnetic Stimulation: Treatment B | Active Comparator | Intermittent theta-primed 10Hz over mPFC |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Guided Meditation VR for Wellness | Device | Selected Modules of Commercially Available "Guided Meditation VR" presented on Valve Index Headset |
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| Measure | Description | Time Frame |
|---|---|---|
| Arm 1 Hypothesis 1 | Primary Outcome will be determined by descriptive feasibility metrics. Feasibility will be determined by number of patients enrolled. | Week 2 |
| Arm 1 Hypothesis 2 | Primary Outcome measure is SF-36 Short Form for all patients. | Week 2 |
| Arm 1 Hypothesis 3 | Primary Outcome measure is the clinician-administered scale that tracks the designated primary disorder. | Week 2 |
| Arm 1 Hypothesis 4 | Primary Outcome measure is the clinician-administered scale that tracks the designated primary disorder. | From Baseline over 10 weeks |
| Arm 2 Hypothesis 1 | Primary Outcome measure is the SF-36 Short Form for all participants. | Week 2 |
| Arm 2 Hypothesis 2 | Primary Outcome measure is the clinician-administered scale that tracks the designated primary disorder. | Week 2 |
| Arm 2-3 Hypothesis 3 | Primary Outcome measure is SF-36 Short Form for all participants. | From Baseline to Week 6 |
| Arm 2-3 Hypothesis 4 | Primary outcome (Treatments A and B). Tolerability will be assessed by side effect profile. |
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Inclusion Criteria for Arm 1:
Exclusion Criteria for Arm 1:
Significant auditory or visual impairment that prevents participants from using Virtual Reality headset.
Neurologic conditions or devices impacting brain circuitry (e.g., ferrous metal in head, seizure disorder, brain tumor, stroke, aneurysm, multiple sclerosis, etc.)
Active substance use disorder or hallucinogen use in last 3 months or any current substance use that puts the participant at increased risk or significant impairment
Dementia or other cognitive disorder making unable to engage in treatment
Any history or diagnosis of Schizophrenia, Schizoaffective Disorder, Delusional Disorder or other psychotic illness that precludes safe participation in trial.
Suicidal risk that precludes safe participation defined as clinical impression that the participant is at significant risk for suicide.
OCD cannot be the primary disorder but can have OCD symptoms
Inability to stop taking any medication that significantly increases cortical excitability (e.g., tricyclic antidepressants, stimulants, clozapine, etc.)
Unstable medical conditions or any current medical condition that could preclude being able to safely participate in this phase of the study (e.g., unstable metabolic abnormality, unstable angina, etc.)
Severe Traumatic Brain Injury
We will exclude non-English speakers because of the need for rapid communication before and during the use of technology.
Significant ongoing litigation or claims that impact research activities, as determined by the research study team. (Research may especially be impacted when mental health or pain is being evaluated for litigation or claims, such as civil and criminal cases, disability claims and worker's compensation).
The following groups will NOT be included.
Inclusion for Arms 2 and 3:
Exclusion for Arms 2 and 3 :
Medical contraindication for neuromodulation (e.g., ferrous metal in head, seizure disorder, brain tumor, stroke, aneurysm, multiple sclerosis, etc.)
Active substance use disorder in last 3 months or any current substance use that puts the participant at increased risk or significant impairment
Dementia or other cognitive disorder making unable to engage in treatment
Any history or diagnosis of Schizophrenia, Schizoaffective Disorder, delusional Disorder or other psychotic illness that precludes safe participation in trial
Suicidal risk that precludes safe participation defined as clinical impression that the participant is at significant risk for suicide
OCD cannot be the primary disorder but can have OCD symptoms
Inability to stop taking any medication that significantly lowers the seizure threshold (e.g., tricyclic antidepressants, clozapine, etc.)
Current, planned, or suspected pregnancy
Unstable medical conditions or any current medical condition that could preclude being able to safely participate in TMS treatment (e.g., unstable metabolic abnormality, unstable angina, etc.)
Severe Traumatic Brain Injury
We will exclude non-English speakers because of the need for rapid communication during the delivery of treatments
Significant ongoing litigation or claims that impact research activities, as determined by the research study team. (Research may especially be impacted when mental health or pain is being evaluated for litigation or claims, such as civil and criminal cases, disability claims and worker's compensation).
The following groups will NOT be included.
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| Name | Affiliation | Role |
|---|---|---|
| F. Andrew Kozel, M.D., M.S.C.R., D.F.A.P.A. | Florida State University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Florida State University | Tallahassee | Florida | 32306 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40224597 | Derived | Senda MC, Johnson KA, Taylor IM, Jensen MM, Hou Y, Kozel FA. A Pilot Trial of Stepwise Implementation of Virtual Reality Mindfulness and Accelerated Transcranial Magnetic Stimulation Treatments for Dysphoria in Neuropsychiatric Disorders. Depress Anxiety. 2023 Nov 22;2023:9025984. doi: 10.1155/2023/9025984. eCollection 2023. | |
| 38780528 |
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| Accelerated Transcranial Magnetic Stimulation: MagVenture Transcranial Magnetic Stimulation (Treatment Coil Cool B70 AP) | Device | MagVenture Transcranial Magnetic Stimulation (Treatment Coil Cool B70 AP) |
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| Accelerated Transcranial Magnetic Stimulation: MagVenture Transcranial Magnetic Stimulation (Cool D-B80 AP) | Device | MagVenture Transcranial Magnetic Stimulation (Cool D-B80 AP) |
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| Week 2 |
| Arm 2-3 Hypothesis 4-Treatment B | Primary outcome (Treatments A and B). Tolerability will be assessed by side effect profile. | Treatment B-Week 6 |
| Arm 3 Hypothesis 5 | Primary Outcome measure is the SF-36 Short Form for all participants. Significantly greater improvement in rating scores from baseline of Treatment A Exit Visit ("Follow Up A1" or "Follow Up A5") to "Follow Up B1" will be tested (t-test). | Treatment B - Week 2 |
| Spitz AM, Senda MC, Johnson KA, Taylor IM, Jensen MM, Kozel FA. The Relationship of Anxious Arousal With Treatment of Dysphoria Using Virtual Reality Mindfulness and 2 Accelerated Transcranial Magnetic Stimulation Protocols. J Clin Psychiatry. 2024 May 22;85(2):23m15195. doi: 10.4088/JCP.23m15195. |