A Phase 2 interventional study of Transcranial Phoobiomodulation (tPBM) in Bipolar Disorder, sponsored by Paolo Cassano. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2025-08-28.
Sponsored by Paolo Cassano · Phase 2, Interventional, and Treatment
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.
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.
1,602 studies on the registry are indexed under Bipolar Disorder; 255 are open to participants now.
This study's enrollment of 13 is below the median of 64 across 1,223 interventional studies indexed under Bipolar Disorder.
Browse Bipolar Disorder studies →Paolo Cassano is the lead sponsor of 2 studies on the registry; none are open to participants now.
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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.
Also known as: Transcranial Light Therapy, Low Level Laser-Light Therapy
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
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
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
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
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.
| Milestone | Transcranial Light Therapy |
|---|---|
| Started | 4 |
| Completed | 4 |
| Not completed | 0 |
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.
| A.U. | Transcranial Light Therapy Subjects |
|---|---|
| Sham Stimulation BOLD Signal | 6611.645 ± 794.5616 |
| Active Stimulation BOLD Signal | 6666.398 ± 784.01 |
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.
| A.U. | Transcranial Light Therapy Subjects |
|---|---|
| Day 1 Active BOLD Signal | 6666.398 ± 784.01 |
| Day 5 Active BOLD Signal | 6891.237 ± 412.7808 |
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.
| units on a scale | Subjects |
|---|---|
| IGT Baseline | 3750 ± 805.19 |
| IGT Day 1 | 4425 ± 448.14 |
| IGT Day 5 | 4512.5 ± 586.48 |
| IGT Follow-Up | 4637.5 ± 432.77 |
| IGT Net Gain Baseline to Day 5 | 762.5 ± 228.67 |
| BIS Baseline | 69.75 ± 8.77 |
| BIS Day 5 | 70.5 ± 4.51 |
| BIS Follow Up | 71.25 ± 8.01 |
| BIS Change Baseline to Day 5 | 0.75 ± 5.38 |
| BIS Change Baseline to Follow Up | 1.5 ± 8.22 |
| BRIEF-A Baseline | 41.75 ± 27.18 |
| BRIEF-A Day 5 | 58 ± 24.68 |
| BRIEF-A Follow Up | 41.25 ± 24.53 |
| BRIEF-A Change Baseline to Day 5 | 16.25 ± 25.86 |
| BRIEF-A Change Baseline to Follow Up | -0.5 ± 4.12 |
| I-7 Impulsiveness Baseline | 9.75 ± 5.31 |
| I-7 Impulsiveness Day 5 | 9 ± 4.08 |
| I-7 Impulsiveness Follow Up | 8.25 ± 3.59 |
| I-7 Impulsiveness Change Baseline to Day 5 | -0.75 ± 2.99 |
| I-7 Impulsiveness Change Baseline to Follow Up | -1.5 ± 2.38 |
| I-7 Venturesomeness Baseline | 6.5 ± 3.51 |
| I-7 Venturesomeness Day 5 | 6.25 ± 3.30 |
| I-7 Venturesomeness Follow Up | 5.25 ± 3.77 |
| I-7 Venturesomeness Change Baseline to Day 5 | -0.25 ± 1.26 |
| I-7 Venturesomeness Change Baseline to Follow Up | -1.25 ± 0.96 |
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.
| score on a scale | Subjects |
|---|---|
| MOODS-SR Baseline | 18.5 ± 23.44 |
| MOODS-SR Day 5 | 21.5 ± 26.41 |
| MOODS-SR Follow Up | 13.5 ± 17.84 |
| MOODS-SR Change Baseline to Day 5 | 3 ± 8.83 |
| MOODS-SR Change Baseline to Follow Up | -5 ± 5.83 |
Collected over Adverse events were collected at all visits apart from screening (Baseline, Day 1-5, Follow Up). Adverse events were also collected during a clinician check-in between Day 5 and Follow Up, approximately 2-3 days after Day 5. Baseline occurred approximately 1 week prior to Day 1. Treatment Days 2-5 were scheduled for the following week (daily); 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.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Subjects | 0/4 (0%) | 0/4 (0%) | 3/4 (75%) |
| Event | Subjects |
|---|---|
| Skin WarmingSkin and subcutaneous tissue disorders | 3/4 |
| Skin Reddening Under DiodeSkin and subcutaneous tissue disorders | 3/4 |
| Cold-like Virus/Common ColdInfections and infestations | 2/4 |
| Pimple on Forehead at Diode LocationSkin and subcutaneous tissue disorders | 1/4 |
| Visual IllusionPsychiatric disorders | 1/4 |
| Age, Categorical(Participants) | Subjects |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 4 |
| >=65 years | 0 |
| Age, Continuous(years) | Subjects |
|---|---|
| Mean | 30.5 ± 4.51 |
| Sex: Female, Male(Participants) | Subjects |
|---|---|
| Female | 3 |
| Male | 1 |
| Ethnicity (NIH/OMB)(Participants) | Subjects |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 4 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Subjects |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 1 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 3 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(participants) | Subjects |
|---|---|
| United States | 4 |
| Barrat Impulsiveness Scale (BIS)(units on a scale) | Subjects |
|---|---|
| Mean | 69.75 ± 8.77 |
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Paolo Cassano