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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-053 | Other Identifier | PVAMC IRB | |
| 1633742 | Other Identifier | PVAMC IRB |
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This study tests the efficacy of combining non-invasive brain stimulation, called transcranial direct current stimulation (tDCS), with virtual reality exposure as a treatment for Veterans with chronic posttraumatic stress disorder (PTSD). Investigators tested whether this intervention improves PTSD symptoms and improves quality of life. Results from this study may be used to develop a new non-medication approach to treating chronic PTSD.
PTSD is highly prevalent in Veterans and is associated with significant psychiatric and medical comorbidity, as well as poor quality of life. Despite its prevalence and impact, the success of currently available treatments is mixed, highlighting the need for novel approaches that aim to reduce symptoms and improve outcomes. Prior research demonstrated that reduced activity in a part of the brain, the ventromedial prefrontal cortex (VMPFC), is associated with an inability to regulate fear responses, preventing the generation of safety memories and allowing PTSD symptoms to persist. Targeting the VMPFC with non-invasive electrical brain stimulation may therefore alleviate these symptoms.
Transcranial direct current stimulation (tDCS) is a type of non-invasive brain stimulation that may enhance the likelihood of neuronal activity in the VMPFC. In doing so, tDCS prepares the brain to respond to external stimuli and to facilitate learning and memory. Because therapeutic success from exposure to trauma-related content - as used in exposure-based therapy for PTSD - is thought to be based on an adaptive learning process, applying tDCS in combination with exposure to trauma cues may effectively boost exposure-based learning. In this study, investigators at the VA Providence Healthcare System will use a standardized virtual reality (VR) setting to deliver trauma-related content. The virtual reality setting involves three, 8-minute driving scenarios, constituting one VR session, which consist of VR stimuli (sights, sounds, smells, etc.) often encountered in combat training and in theater.
Eligible participants will be randomized to receive six sessions of either active tDCS plus virtual reality (tDCS+VR) or sham tDCS+VR. Clinical and self-report assessments will be completed at baseline, midpoint, and endpoint, as well as 1 and 3 months following the final VR session. Primary outcome measures occur at the 1 month timepoint. Psychophysiology (skin conductance reactivity) will be collected throughout each VR session to capture habituation. Participants will also undergo a MRI before and after completion of all six active or sham tDCS+VR sessions to assess change over time. Additionally, MRI data will be used for electrical field modeling to predict treatment response based on individually obtained electrical field values in PTSD relevant neural circuitry. Participants may also choose to participate in an optional pre-active or sham tDCS+VR session EEG and an optional 1-month follow-up MRI.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active Stimulation | Active Comparator | Active stimulation (tDCS) will be used in the dose of 2mA /25 min per day, for 6 sessions over the course of 2 weeks (3 sessions per week). |
|
| Sham Stimulation | Sham Comparator | Sham tDCS uses the device study mode (10 µA over 15 ms current pulse applied every 550 ms, 3ms peak current). This process will be used for each of the 6 sessions during a 2 week period. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Active stimulation | Device | For active tDCS, the investigators will use a 1x1 configuration with the anode placed over EEG coordinates AF7/Fp1/AF3 (using the 10-20 EEG convention) and the cathode between EEG coordinate OZ and the contralateral mastoid (covering approximately PO8/P8). The investigators will use 3x3 cm sponge covered electrodes and a 2mA current for 25 minutes per session. |
| Measure | Description | Time Frame |
|---|---|---|
| Post-traumatic Stress Disorder Checklist for DSM-5 (PCL-5) Total Score | The PCL-5 is a 20-item self-report measure that assesses the 20 DSM-5 symptoms of PTSD. Items are rated on how much the symptom bothered the respondent in the past month (0 = "not at all bothered by" to 4 = "extremely bothered "). A total symptom severity score (range: 0-80) can be obtained by summing the scores for each of the 20 items, with higher scores indicating more severe PTSD symptoms. PCL-5 scores at 1 month was the primary symptom outcome measure for this study. | Baseline, Midpoint (1 week after VR session 3), Endpoint (2 weeks after VR session 6), 1 Month Follow-up, 3 Month Follow-Up |
| Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ) | The 16-item QLESQ (short form) evaluates quality of life and other areas of change related to functioning outside of symptom domains (e.g., physical health, mood, leisure time activities, social relationships, etc.). Items are rated on how satisfied the respondent has been in the past week (1 = "very poor" to 5 = "very good "). A total raw score (range: 16-80). Higher outcomes indicate better quality of life, greater enjoyment, and satisfaction. | Baseline, Endpoint (2 weeks after VR session 6), 1 Month Follow-Up, 3 Month Follow-Up |
| Psychophysiology (Skin Conductance Reactivity; SCR) | Psychophysiology will include skin conductance reactivity to specific trauma context virtual reality (VR) cues presented in the VR scenario. SCR to VR events will be measured by the phasic responses that occur after the presentation of discreet VR events. SCR will be compared from baseline to end of tDCS+VR, to correlate these measures and evaluate changes attributable to active tDCS+VR compared to sham. | Measured during each tDCS+VR session, each session up to 1 hour |
| Measure | Description | Time Frame |
|---|---|---|
| Inventory of Depressive Symptomatology Self-Report (IDSSR) | The 28-item IDSSR is a self-report measure of depressive symptom severity. Each item is rated on a scale of 0 to 3 by the participant for a total minimum score of 0 and a maximum score of 84. A higher score on the IDSSR indicates increased depressive symptom severity. | Baseline, Midpoint (1 week after VR session 3), Endpoint (2 weeks after VR session 6), 1 Month Follow-up, 3 Month Follow-Up |
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Inclusion Criteria:
Exclusion Criteria:
Contraindications to MRI or tDCS, including:
Other exclusions:
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| Name | Affiliation | Role |
|---|---|---|
| Noah S. Philip, MD | Providence VA Medical Center, Providence, RI | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Providence VA Medical Center, Providence, RI | Providence | Rhode Island | 02908-4734 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38446471 | Background | van 't Wout-Frank M, Arulpragasam AR, Faucher C, Aiken E, Shea MT, Jones RN, Greenberg BD, Philip NS. Virtual Reality and Transcranial Direct Current Stimulation for Posttraumatic Stress Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2024 May 1;81(5):437-446. doi: 10.1001/jamapsychiatry.2023.5661. |
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Following enrollment, 10 Veterans were not randomized. Of these 10 Veterans, five were ineligible, three were lost to contact, and 2 were discontinued due to other concerns.
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| ID | Title | Description |
|---|---|---|
| FG000 | Active Stimulation | Active stimulation (tDCS) will be used in the dose of 2mA /25 min per day, for 6 sessions over the course of 2 weeks (3 sessions per week). Active stimulation: For active tDCS, the investigators will use a 1x1 configuration with the anode placed over EEG coordinates AF7/Fp1/AF3 (using the 10-20 EEG convention) and the cathode between EEG coordinate OZ and the contralateral mastoid (covering approximately PO8/P8). The investigators will use 3x3 cm sponge covered electrodes and a 2mA current for 25 minutes per session. Virtual Reality (VR): Participants will undergo VR exposure to trauma-related context. |
| FG001 | Sham Stimulation | Sham tDCS uses the device study mode (10 µA over 15 ms current pulse applied every 550 ms, 3ms peak current). This process will be used for each of the 6 sessions during a 2 week period. Sham stimulation: For sham tDCS, the investigators will use the same electrode and sponge configuration as active tDCS, but using the device study mode (10 µA over 15 ms current pulse applied every 550 ms, 3ms peak current). Virtual Reality (VR): Participants will undergo VR exposure to trauma-related context. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Active Stimulation | Active stimulation (tDCS) will be used in the dose of 2mA /25 min per day, for 6 sessions over the course of 2 weeks (3 sessions per week). Active stimulation: For active tDCS, the investigators will use a 1x1 configuration with the anode placed over EEG coordinates AF7/Fp1/AF3 (using the 10-20 EEG convention) and the cathode between EEG coordinate OZ and the contralateral mastoid (covering approximately PO8/P8). The investigators will use 3x3 cm sponge covered electrodes and a 2mA current for 25 minutes per session. Virtual Reality (VR): Participants will undergo VR exposure to trauma-related context. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Post-traumatic Stress Disorder Checklist for DSM-5 (PCL-5) Total Score | The PCL-5 is a 20-item self-report measure that assesses the 20 DSM-5 symptoms of PTSD. Items are rated on how much the symptom bothered the respondent in the past month (0 = "not at all bothered by" to 4 = "extremely bothered "). A total symptom severity score (range: 0-80) can be obtained by summing the scores for each of the 20 items, with higher scores indicating more severe PTSD symptoms. PCL-5 scores at 1 month was the primary symptom outcome measure for this study. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Midpoint (1 week after VR session 3), Endpoint (2 weeks after VR session 6), 1 Month Follow-up, 3 Month Follow-Up |
|
Up to three months
Adverse events were spontaneously reported by participants and systematically assessed through a side effects questionnaire that was administered before and after each tDCS + virtual reality session.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Active Stimulation | Active stimulation (tDCS) will be used in the dose of 2mA /25 min per day, for 6 sessions over the course of 2 weeks (3 sessions per week). Active stimulation: For active tDCS, the investigators will use a 1x1 configuration with the anode placed over EEG coordinates AF7/Fp1/AF3 (using the 10-20 EEG convention) and the cathode between EEG coordinate OZ and the contralateral mastoid (covering approximately PO8/P8). The investigators will use 3x3 cm sponge covered electrodes and a 2mA current for 25 minutes per session. Virtual Reality (VR): Participants will undergo VR exposure to trauma-related context. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Exacerbation of chronic gastrointestinal illness | Gastrointestinal disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | Systematic Assessment |
The COVID-19 pandemic significantly impacted recruitment, retention (particularly at the 3-month timepoint), and plausibly outcomes related to quality of life and social and occupational function.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Noah S Philip, MD | Center for Neurorestoration and Neurotechnology, VA Providence Healthcare System | 4012737100 | 16200 | noah_philip@brown.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 8, 2023 | Jun 10, 2024 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jul 13, 2022 | Jun 10, 2024 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D013313 | Stress Disorders, Post-Traumatic |
| ID | Term |
|---|---|
| D040921 | Stress Disorders, Traumatic |
| D000068099 | Trauma and Stressor Related Disorders |
| D001523 | Mental Disorders |
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Participants are assigned to receive either active or sham stimulation during the tDCS+VR sessions in parallel for the duration of the study
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double blind tDCS
|
|
| Sham stimulation | Device | For sham tDCS, the investigators will use the same electrode and sponge configuration as active tDCS, but using the device study mode (10 µA over 15 ms current pulse applied every 550 ms, 3ms peak current). |
|
|
| Virtual Reality (VR) | Other | Participants will undergo VR exposure to trauma-related context. |
|
| Social and Occupational Function Scale (SOFAS) | The SOFAS is a scale that focuses on the individual's level of social and occupational functioning and is not directly influenced by the overall severity of the individual's psychological symptoms. Any impairment in social and occupational functioning that is due to general medical conditions is considered in making the SOFAS rating. The SOFAS is usually used to rate functioning for the current period (i.e., the level of functioning at the time of the evaluation). Scores range from 0 to 100, with higher scores indicating better social and occupational functioning. | Baseline, Endpoint (2 weeks after VR session 6), 1 Month Follow-Up, 3 Month Follow-Up |
| Clinician Administered PTSD Scale for the DSM-5 (CAPS-5) | The CAPS-5 is the gold standard in clinician-assessed PTSD symptoms. The CAPS-5 is a 30-item structured interview that can be used to make current (past month) diagnosis of PTSD, make lifetime diagnosis of PTSD, and assess PTSD symptoms over the past week. In addition to assessing the 20 DSM-5 PTSD symptoms, questions target the onset and duration of symptoms, subjective distress, impact of symptoms on social and occupational functioning, improvement in symptoms since a previous CAPS administration, overall response validity, overall PTSD severity, and specifications for the dissociative subtype (depersonalization and derealization). An interviewee's total severity score on the CAPS-5 represents the sum of the individual severity scores (0-4) for each of the 20 PTSD symptoms; total scores range from 0-80, with higher scores indicating more severe PTSD symptoms. | Baseline, Endpoint (2 weeks after VR session 6), 1 Month Follow-Up, 3 Month Follow-Up |
| BG001 | Sham Stimulation | Sham tDCS uses the device study mode (10 µA over 15 ms current pulse applied every 550 ms, 3ms peak current). This process will be used for each of the 6 sessions during a 2 week period. Sham stimulation: For sham tDCS, the investigators will use the same electrode and sponge configuration as active tDCS, but using the device study mode (10 µA over 15 ms current pulse applied every 550 ms, 3ms peak current). Virtual Reality (VR): Participants will undergo VR exposure to trauma-related context. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| PTSD Checklist for DSM-5 (PCL-5) | Total symptom severity score (range: 0-80) with higher scores indicating more severe PTSD symptoms. | Mean | Standard Deviation | score on a scale |
|
| Clinician-Administered PTSD Scale for DSM-5 | Total scores range from 0-80, with higher scores indicating more severe PTSD symptoms. | Mean | Standard Deviation | score on a scale |
|
| Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ) | The 16-item QLESQ (short form) evaluates quality of life and other areas of change related to functioning outside of symptom domains (e.g., physical health, mood, leisure time activities, social relationships, etc.). Items are rated on how satisfied the respondent has been in the past week (1 = "very poor" to 5 = "very good "). A total raw score (range: 16-80). Higher outcomes indicate better quality of life, greater enjoyment, and satisfaction. | Mean | Standard Deviation | score on a scale |
|
| Social and Occupational Function Scale (SOFAS) | Scores range from 0 to 100, with higher scores indicating better social and occupational functioning. | Mean | Standard Deviation | score on a scale |
|
| Inventory of Depressive Symptomatology Self Report (IDSSR) | Total minimum score of 0 and a maximum score of 84. A higher score on the IDSSR indicates increased depressive symptom severity. | Mean | Standard Deviation | score on a scale |
|
| OG001 | Sham Stimulation | Sham tDCS uses the device study mode (10 µA over 15 ms current pulse applied every 550 ms, 3ms peak current). This process will be used for each of the 6 sessions during a 2 week period. Sham stimulation: For sham tDCS, the investigators will use the same electrode and sponge configuration as active tDCS, but using the device study mode (10 µA over 15 ms current pulse applied every 550 ms, 3ms peak current). Virtual Reality (VR): Participants will undergo VR exposure to trauma-related context. |
|
|
| Primary | Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ) | The 16-item QLESQ (short form) evaluates quality of life and other areas of change related to functioning outside of symptom domains (e.g., physical health, mood, leisure time activities, social relationships, etc.). Items are rated on how satisfied the respondent has been in the past week (1 = "very poor" to 5 = "very good "). A total raw score (range: 16-80). Higher outcomes indicate better quality of life, greater enjoyment, and satisfaction. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Endpoint (2 weeks after VR session 6), 1 Month Follow-Up, 3 Month Follow-Up |
|
|
|
| Primary | Psychophysiology (Skin Conductance Reactivity; SCR) | Psychophysiology will include skin conductance reactivity to specific trauma context virtual reality (VR) cues presented in the VR scenario. SCR to VR events will be measured by the phasic responses that occur after the presentation of discreet VR events. SCR will be compared from baseline to end of tDCS+VR, to correlate these measures and evaluate changes attributable to active tDCS+VR compared to sham. | Posted | Mean | Standard Error | microsiemens (μS) | Measured during each tDCS+VR session, each session up to 1 hour |
|
|
|
| Secondary | Inventory of Depressive Symptomatology Self-Report (IDSSR) | The 28-item IDSSR is a self-report measure of depressive symptom severity. Each item is rated on a scale of 0 to 3 by the participant for a total minimum score of 0 and a maximum score of 84. A higher score on the IDSSR indicates increased depressive symptom severity. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Midpoint (1 week after VR session 3), Endpoint (2 weeks after VR session 6), 1 Month Follow-up, 3 Month Follow-Up |
|
|
|
| Secondary | Social and Occupational Function Scale (SOFAS) | The SOFAS is a scale that focuses on the individual's level of social and occupational functioning and is not directly influenced by the overall severity of the individual's psychological symptoms. Any impairment in social and occupational functioning that is due to general medical conditions is considered in making the SOFAS rating. The SOFAS is usually used to rate functioning for the current period (i.e., the level of functioning at the time of the evaluation). Scores range from 0 to 100, with higher scores indicating better social and occupational functioning. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Endpoint (2 weeks after VR session 6), 1 Month Follow-Up, 3 Month Follow-Up |
|
|
|
| Secondary | Clinician Administered PTSD Scale for the DSM-5 (CAPS-5) | The CAPS-5 is the gold standard in clinician-assessed PTSD symptoms. The CAPS-5 is a 30-item structured interview that can be used to make current (past month) diagnosis of PTSD, make lifetime diagnosis of PTSD, and assess PTSD symptoms over the past week. In addition to assessing the 20 DSM-5 PTSD symptoms, questions target the onset and duration of symptoms, subjective distress, impact of symptoms on social and occupational functioning, improvement in symptoms since a previous CAPS administration, overall response validity, overall PTSD severity, and specifications for the dissociative subtype (depersonalization and derealization). An interviewee's total severity score on the CAPS-5 represents the sum of the individual severity scores (0-4) for each of the 20 PTSD symptoms; total scores range from 0-80, with higher scores indicating more severe PTSD symptoms. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Endpoint (2 weeks after VR session 6), 1 Month Follow-Up, 3 Month Follow-Up |
|
|
|
| 0 |
| 26 |
| 2 |
| 26 |
| 18 |
| 26 |
| EG001 | Sham Stimulation | Sham tDCS uses the device study mode (10 µA over 15 ms current pulse applied every 550 ms, 3ms peak current). This process will be used for each of the 6 sessions during a 2 week period. Sham stimulation: For sham tDCS, the investigators will use the same electrode and sponge configuration as active tDCS, but using the device study mode (10 µA over 15 ms current pulse applied every 550 ms, 3ms peak current). Virtual Reality (VR): Participants will undergo VR exposure to trauma-related context. | 0 | 28 | 2 | 28 | 18 | 28 |
| Syncopal episode | General disorders | Non-systematic Assessment |
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| Treatment-emergent suicidal ideation | Psychiatric disorders | Non-systematic Assessment |
|
| Neck pain | General disorders | Systematic Assessment |
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| Head pain | General disorders | Systematic Assessment |
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| Scalp pain | General disorders | Systematic Assessment |
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| Tingling | General disorders | Systematic Assessment |
|
| Itching | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Burning | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Redness | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Ringing or buzzing in ears | General disorders | Systematic Assessment |
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| Change in mood | Psychiatric disorders | Systematic Assessment |
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| Changes in concentration | General disorders | Systematic Assessment |
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| Sleepy, drowsy, or fatigue | General disorders | Systematic Assessment |
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| Flickering lights | General disorders | Systematic Assessment |
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| Blurry vision | General disorders | Systematic Assessment |
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| Dizziness or lightheadedness | General disorders | Systematic Assessment |
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| Nausea | General disorders | Systematic Assessment |
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| 1 month follow-up |
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| 3-month follow-up |
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| VR Session 3 |
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| VR Session 4 |
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| VR Session 5 |
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| VR Session 6 |
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| Endpoint |
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| 1 Month Follow-Up |
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| 3 Month Follow-Up |
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| 1 Month Follow-Up |
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| 3 Month Follow-Up |
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| 1 Month Follow-Up |
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| 3 Month Follow-Up |
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