Bipolar Disorder
Conditions
Keywords
Bipolar, Bipolar Disorder
Brief summary
Transcranial light therapy, or transcranial photobiomodulation (tPBM), is a treatment that stimulates the brain by applying near-infrared light to the forehead. Transcranial light therapy has been found to promote brain metabolism, which may help improve executive function in people with bipolar disorder. The research team proposes a novel approach to treating bipolar disorder by using transcranial light therapy.
Detailed description
This study involves a virtual screening visit, 7 in-office visits, and a virtual check-in call with a clinician. Participation will last approximately 3 weeks in total. Participants will attend a baseline visit during which they will complete mood questionnaires and a gambling task. Participants will then receive five treatments of transcranial light therapy over one week. The first and last of these treatments will be administered while the participant is in an MRI scanner. At the first visit, participants will also receive a sham tPBM treatment, meaning that the device will simulate real treatment, but will not actually apply the near-infrared light. The check-in call will occur approximately 2-3 days after the final treatment visit. This will be a brief call with a study clinician to check-in on the participant's mental and physical health. The follow up visit will occur approximately one week after the final visit. Subjects will be asked to complete mood questionnaires and/or gambling tasks during the first and fifth treatment visits, as well as at the follow up visit.
Interventions
DEVICETranscranial Phoobiomodulation (tPBM)
Transcranial light therapy penetrates the skin and brain using light energy; this makes transcranial light therapy noninvasive. Transcranial light therapy may activate under-stimulated brain regions.
Sponsors
Paolo Cassano
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
During the first treatment visit within the MRI, participants will receive one active tPBM treatment and one sham tPBM treatment. Participants will be blinded as to the order in which they receive these treatments.
Intervention model description
All participants will receive five active tPBM treatments and one sham tPBM treatment.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Adults between the ages of 18 and 65 * Diagnosis of bipolar disorder * Currently experiencing symptoms of impulsivity * Vision normal or corrected to normal with contacts
Exclusion criteria
* Currently in depressive, manic, or mixed episode * Currently psychotic * Judged to be at serious and imminent suicidal risk * Currently in alcohol or substance use disorder (meeting criteria in the past 3 months) * Unstable medical conditions * Inability to consent or to complete study procedures * Failure to meet standard MRI safety requirements (e.g. claustrophobia, non-removable piercings, implanted medical devices, other non-removable metals) * Changes in medications or use of augmentative devices and other interventions in the 2 weeks prior to the study * Participation in other clinical research trials that may influence primary outcomes or adherence to the proposed study * Current pregnancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Test the Effect of Transcranial Photobiomodulation (tPBM) on Cerebral Blood Flow (CBF) | Day 1 of tPBM Treatment | Compare blood-oxygenation-level-dependent (BOLD) signal during sham stimulation at Day 1 versus BOLD signal during active stimulation at Day 1. Increased BOLD signal is thought to reflect increased brain activity, and thus a positive outcome. In this specific case, higher BOLD signal during active as compared to sham treatment in the right dorsolateral prefrontal cortex (rDLPFC) is thought to reflect target engagement, that is the tPBM device which is placed on the right forehead is in fact irradiating and having an effect on brain function within the rDLPFC. |
| Test Effect of tPBM on CBF | Day 1 and Day 5 | Compare BOLD signal during active stimulation at Day 1 versus active stimulation at Day 5. Greater BOLD signal at Day 5 compared to Day 1 would indicate an increase in brain activity following active treatment, supporting tPBM target engagement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Test the Effect of tPBM on Impaired Decision Making | Baseline to Follow-Up | Improvement in decision making will be evaluated by an increase in net gain at the Iowa Gambling Task (IGT) (higher score=better outcome, min score -3000, max score 7000), decrease in Barratt Impulsiveness Scale (BIS) score (min 30, max 120, lower score=better outcome), decrease in Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) score (min 0, max 140, lower score=better outcome), and a decrease in I-7 Impulsiveness and Venturesomeness Questionnaire score (lower score=better outcome, Impulsiveness subscale: min 0, max 19, Venturesomeness subscale: min 0, max 15). All items are evaluated at Day 5 and Follow-up visit relative to Baseline. Baseline occurred approximately 1 week prior to Day 1. Treatment Days 2-5 were scheduled for the following week, ideally once daily, however the schedule allowed for flexibility, with Day 5 occurring no later than 10 days after Day 1. Follow-up occurred approximately 1 week after Day 5, or approximately 3 weeks after Baseline. |
| Test the Effect of Repeated t-PBM Sessions on Mood Symptoms (MOODS-SR) in Subjects With Bipolar Disorder (BD) | Baseline to Follow Up | Repeated t-PBM sessions on the rDLPFC will significantly decrease the total Mood Spectrum-Self Report (MOODS-SR) (min 0, max 154, lower score= better outcome) score at Day 5 and Follow-Up visit relative to Baseline. The scale was evaluated at Day 5 and Follow-up visit relative to Baseline. Baseline occurred approximately 1 week prior to Day 1. Treatment Days 2-5 were scheduled for the following week, ideally once daily, however the schedule allowed for flexibility, with Day 5 occurring no later than 10 days after Day 1. Follow-up occurred approximately 1 week after Day 5, or approximately 3 weeks after Baseline. |
Countries
United States
Participant flow
Recruitment details
Recruitment took place at Massachusetts General Hospital between July 2022 and April 2024. Subjects were recruited through a variety of methods, including online advertisements and surveys, flyers, and referrals from providers and other research studies.
Pre-assignment details
Subjects underwent screening procedures to determine eligibility. A majority of subjects were excluded for not meeting the impulsivity threshold. Other subjects were excluded due to current alcohol or substance use disorder or were lost to follow up.
Participants by arm
| Arm | Count |
|---|---|
| Subjects Subjects who passed screening and completed all study procedures. | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | Subjects |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Age, Continuous | 30.5 years STANDARD_DEVIATION 4.51 |
| Barrat Impulsiveness Scale (BIS) | 69.75 units on a scale STANDARD_DEVIATION 8.77 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 3 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
Test Effect of tPBM on CBF
Compare BOLD signal during active stimulation at Day 1 versus active stimulation at Day 5. Greater BOLD signal at Day 5 compared to Day 1 would indicate an increase in brain activity following active treatment, supporting tPBM target engagement.
Time frame: Day 1 and Day 5
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Transcranial Light Therapy Subjects | Test Effect of tPBM on CBF | Day 1 Active BOLD Signal | 6666.398 A.U. | Standard Deviation 784.01 |
| Transcranial Light Therapy Subjects | Test Effect of tPBM on CBF | Day 5 Active BOLD Signal | 6891.237 A.U. | Standard Deviation 412.7808 |
Comparison: The small sample size did not allow for statistical tests. Therefore, we calculated percent difference between active stimulation timepoints (Day 1 vs Day 5).
Comparison: We evaluated the effect size of the difference between active stimulation timepoints (Day 1 vs Day 5) using Cohen's d.
Primary
Test the Effect of Transcranial Photobiomodulation (tPBM) on Cerebral Blood Flow (CBF)
Compare blood-oxygenation-level-dependent (BOLD) signal during sham stimulation at Day 1 versus BOLD signal during active stimulation at Day 1. Increased BOLD signal is thought to reflect increased brain activity, and thus a positive outcome. In this specific case, higher BOLD signal during active as compared to sham treatment in the right dorsolateral prefrontal cortex (rDLPFC) is thought to reflect target engagement, that is the tPBM device which is placed on the right forehead is in fact irradiating and having an effect on brain function within the rDLPFC.
Time frame: Day 1 of tPBM Treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Transcranial Light Therapy Subjects | Test the Effect of Transcranial Photobiomodulation (tPBM) on Cerebral Blood Flow (CBF) | Sham Stimulation BOLD Signal | 6611.645 A.U. | Standard Deviation 794.5616 |
| Transcranial Light Therapy Subjects | Test the Effect of Transcranial Photobiomodulation (tPBM) on Cerebral Blood Flow (CBF) | Active Stimulation BOLD Signal | 6666.398 A.U. | Standard Deviation 784.01 |
Comparison: The small sample size did not allow for statistical tests. Therefore, we looked at percent difference between stimulation (Active vs Sham).
Comparison: We evaluated the effect size of the difference between Active and Sham using Cohen's d.
Secondary
Test the Effect of Repeated t-PBM Sessions on Mood Symptoms (MOODS-SR) in Subjects With Bipolar Disorder (BD)
Repeated t-PBM sessions on the rDLPFC will significantly decrease the total Mood Spectrum-Self Report (MOODS-SR) (min 0, max 154, lower score= better outcome) score at Day 5 and Follow-Up visit relative to Baseline. The scale was evaluated at Day 5 and Follow-up visit relative to Baseline. Baseline occurred approximately 1 week prior to Day 1. Treatment Days 2-5 were scheduled for the following week, ideally once daily, however the schedule allowed for flexibility, with Day 5 occurring no later than 10 days after Day 1. Follow-up occurred approximately 1 week after Day 5, or approximately 3 weeks after Baseline.
Time frame: Baseline to Follow Up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Transcranial Light Therapy Subjects | Test the Effect of Repeated t-PBM Sessions on Mood Symptoms (MOODS-SR) in Subjects With Bipolar Disorder (BD) | MOODS-SR Change Baseline to Follow Up | -5 score on a scale | Standard Deviation 5.83 |
| Transcranial Light Therapy Subjects | Test the Effect of Repeated t-PBM Sessions on Mood Symptoms (MOODS-SR) in Subjects With Bipolar Disorder (BD) | MOODS-SR Baseline | 18.5 score on a scale | Standard Deviation 23.44 |
| Transcranial Light Therapy Subjects | Test the Effect of Repeated t-PBM Sessions on Mood Symptoms (MOODS-SR) in Subjects With Bipolar Disorder (BD) | MOODS-SR Day 5 | 21.5 score on a scale | Standard Deviation 26.41 |
| Transcranial Light Therapy Subjects | Test the Effect of Repeated t-PBM Sessions on Mood Symptoms (MOODS-SR) in Subjects With Bipolar Disorder (BD) | MOODS-SR Follow Up | 13.5 score on a scale | Standard Deviation 17.84 |
| Transcranial Light Therapy Subjects | Test the Effect of Repeated t-PBM Sessions on Mood Symptoms (MOODS-SR) in Subjects With Bipolar Disorder (BD) | MOODS-SR Change Baseline to Day 5 | 3 score on a scale | Standard Deviation 8.83 |
p-value: 0.6Wilcoxon signed rank test
p-value: 0.2Wilcoxon signed rank test
Secondary
Test the Effect of tPBM on Impaired Decision Making
Improvement in decision making will be evaluated by an increase in net gain at the Iowa Gambling Task (IGT) (higher score=better outcome, min score -3000, max score 7000), decrease in Barratt Impulsiveness Scale (BIS) score (min 30, max 120, lower score=better outcome), decrease in Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) score (min 0, max 140, lower score=better outcome), and a decrease in I-7 Impulsiveness and Venturesomeness Questionnaire score (lower score=better outcome, Impulsiveness subscale: min 0, max 19, Venturesomeness subscale: min 0, max 15). All items are evaluated at Day 5 and Follow-up visit relative to Baseline. Baseline occurred approximately 1 week prior to Day 1. Treatment Days 2-5 were scheduled for the following week, ideally once daily, however the schedule allowed for flexibility, with Day 5 occurring no later than 10 days after Day 1. Follow-up occurred approximately 1 week after Day 5, or approximately 3 weeks after Baseline.
Time frame: Baseline to Follow-Up
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Transcranial Light Therapy Subjects | Test the Effect of tPBM on Impaired Decision Making | IGT Baseline | 3750 units on a scale | Standard Deviation 805.19 |
| Transcranial Light Therapy Subjects | Test the Effect of tPBM on Impaired Decision Making | IGT Follow-Up | 4637.5 units on a scale | Standard Deviation 432.77 |
| Transcranial Light Therapy Subjects | Test the Effect of tPBM on Impaired Decision Making | BIS Follow Up | 71.25 units on a scale | Standard Deviation 8.01 |
| Transcranial Light Therapy Subjects | Test the Effect of tPBM on Impaired Decision Making | BIS Change Baseline to Day 5 | 0.75 units on a scale | Standard Deviation 5.38 |
| Transcranial Light Therapy Subjects | Test the Effect of tPBM on Impaired Decision Making | I-7 Impulsiveness Day 5 | 9 units on a scale | Standard Deviation 4.08 |
| Transcranial Light Therapy Subjects | Test the Effect of tPBM on Impaired Decision Making | I-7 Venturesomeness Follow Up | 5.25 units on a scale | Standard Deviation 3.77 |
| Transcranial Light Therapy Subjects | Test the Effect of tPBM on Impaired Decision Making | IGT Day 1 | 4425 units on a scale | Standard Deviation 448.14 |
| Transcranial Light Therapy Subjects | Test the Effect of tPBM on Impaired Decision Making | IGT Day 5 | 4512.5 units on a scale | Standard Deviation 586.48 |
| Transcranial Light Therapy Subjects | Test the Effect of tPBM on Impaired Decision Making | IGT Net Gain Baseline to Day 5 | 762.5 units on a scale | Standard Deviation 228.67 |
| Transcranial Light Therapy Subjects | Test the Effect of tPBM on Impaired Decision Making | BIS Baseline | 69.75 units on a scale | Standard Deviation 8.77 |
| Transcranial Light Therapy Subjects | Test the Effect of tPBM on Impaired Decision Making | BIS Day 5 | 70.5 units on a scale | Standard Deviation 4.51 |
| Transcranial Light Therapy Subjects | Test the Effect of tPBM on Impaired Decision Making | BIS Change Baseline to Follow Up | 1.5 units on a scale | Standard Deviation 8.22 |
| Transcranial Light Therapy Subjects | Test the Effect of tPBM on Impaired Decision Making | BRIEF-A Baseline | 41.75 units on a scale | Standard Deviation 27.18 |
| Transcranial Light Therapy Subjects | Test the Effect of tPBM on Impaired Decision Making | BRIEF-A Day 5 | 58 units on a scale | Standard Deviation 24.68 |
| Transcranial Light Therapy Subjects | Test the Effect of tPBM on Impaired Decision Making | BRIEF-A Follow Up | 41.25 units on a scale | Standard Deviation 24.53 |
| Transcranial Light Therapy Subjects | Test the Effect of tPBM on Impaired Decision Making | BRIEF-A Change Baseline to Day 5 | 16.25 units on a scale | Standard Deviation 25.86 |
| Transcranial Light Therapy Subjects | Test the Effect of tPBM on Impaired Decision Making | BRIEF-A Change Baseline to Follow Up | -0.5 units on a scale | Standard Deviation 4.12 |
| Transcranial Light Therapy Subjects | Test the Effect of tPBM on Impaired Decision Making | I-7 Impulsiveness Baseline | 9.75 units on a scale | Standard Deviation 5.31 |
| Transcranial Light Therapy Subjects | Test the Effect of tPBM on Impaired Decision Making | I-7 Impulsiveness Follow Up | 8.25 units on a scale | Standard Deviation 3.59 |
| Transcranial Light Therapy Subjects | Test the Effect of tPBM on Impaired Decision Making | I-7 Impulsiveness Change Baseline to Day 5 | -0.75 units on a scale | Standard Deviation 2.99 |
| Transcranial Light Therapy Subjects | Test the Effect of tPBM on Impaired Decision Making | I-7 Impulsiveness Change Baseline to Follow Up | -1.5 units on a scale | Standard Deviation 2.38 |
| Transcranial Light Therapy Subjects | Test the Effect of tPBM on Impaired Decision Making | I-7 Venturesomeness Baseline | 6.5 units on a scale | Standard Deviation 3.51 |
| Transcranial Light Therapy Subjects | Test the Effect of tPBM on Impaired Decision Making | I-7 Venturesomeness Day 5 | 6.25 units on a scale | Standard Deviation 3.3 |
| Transcranial Light Therapy Subjects | Test the Effect of tPBM on Impaired Decision Making | I-7 Venturesomeness Change Baseline to Day 5 | -0.25 units on a scale | Standard Deviation 1.26 |
| Transcranial Light Therapy Subjects | Test the Effect of tPBM on Impaired Decision Making | I-7 Venturesomeness Change Baseline to Follow Up | -1.25 units on a scale | Standard Deviation 0.96 |
Comparison: The Wilcoxon signed-rank test was used to evaluate changes in the IGT at Baseline vs Day 5 due to the small sample size and distributional assumptions. Effect sizes were calculated using the rank biserial correlation coefficient (r) to estimate the magnitude of change.p-value: 0.15Wilcoxon signed rank test
p-value: 0.038Friedman test
p-value: 0.043Friedman test
p-value: 0.42Wilcoxon signed rank test
p-value: 0.232Wilcoxon signed rank test
p-value: 0.06Wilcoxon signed rank test
p-value: 0.36Wilcoxon signed rank test