Trial Outcomes & Findings for Transcranial Photobiomodulation for Executive Function in Bipolar Disorder (NCT NCT05408637)

Last Updated: 2025-08-28

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

13 participants

Primary outcome timeframe

Day 1 of tPBM Treatment

Results posted on

2025-08-28

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Transcranial Light Therapy Subjects who passed screening and completed all study procedures. All subjects received a sham light therapy treatment followed by an active light therapy treatment at the first MRI session. This was a single-blind procedure. All following transcranial photobiomodulation (tPBM) sessions (Treatment Days 2, 3, 4 and MRI session on Day 5) were active and open-label.
Overall Study STARTED	4
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Transcranial Photobiomodulation for Executive Function in Bipolar Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Subjects n=4 Participants Subjects who passed screening and completed all study procedures.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	30.5 years STANDARD_DEVIATION 4.51 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	4 participants n=5 Participants
Barrat Impulsiveness Scale (BIS)	69.75 units on a scale STANDARD_DEVIATION 8.77 • n=5 Participants

PRIMARY outcome

Timeframe: Day 1 of tPBM Treatment

Outcome measures

Outcome measures
Measure	Transcranial Light Therapy Subjects n=4 Participants Subjects who passed screening and completed all study procedures. All subjects received a sham light therapy treatment followed by an active light therapy treatment at the first MRI session. This was a single-blind procedure.
Test the Effect of Transcranial Photobiomodulation (tPBM) on Cerebral Blood Flow (CBF) Sham Stimulation BOLD Signal	6611.645 A.U. Standard Deviation 794.5616
Test the Effect of Transcranial Photobiomodulation (tPBM) on Cerebral Blood Flow (CBF) Active Stimulation BOLD Signal	6666.398 A.U. Standard Deviation 784.01

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Transcranial Light Therapy Subjects n=4 Participants Subjects who passed screening and completed all study procedures. All subjects received a sham light therapy treatment followed by an active light therapy treatment at the first MRI session. This was a single-blind procedure.
Test Effect of tPBM on CBF Day 1 Active BOLD Signal	6666.398 A.U. Standard Deviation 784.01
Test Effect of tPBM on CBF Day 5 Active BOLD Signal	6891.237 A.U. Standard Deviation 412.7808

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Transcranial Light Therapy Subjects n=4 Participants Subjects who passed screening and completed all study procedures. All subjects received a sham light therapy treatment followed by an active light therapy treatment at the first MRI session. This was a single-blind procedure.
Test the Effect of tPBM on Impaired Decision Making IGT Baseline	3750 units on a scale Standard Deviation 805.19
Test the Effect of tPBM on Impaired Decision Making IGT Day 1	4425 units on a scale Standard Deviation 448.14
Test the Effect of tPBM on Impaired Decision Making IGT Day 5	4512.5 units on a scale Standard Deviation 586.48
Test the Effect of tPBM on Impaired Decision Making IGT Follow-Up	4637.5 units on a scale Standard Deviation 432.77
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
Test the Effect of tPBM on Impaired Decision Making BIS Baseline	69.75 units on a scale Standard Deviation 8.77
Test the Effect of tPBM on Impaired Decision Making BIS Day 5	70.5 units on a scale Standard Deviation 4.51
Test the Effect of tPBM on Impaired Decision Making BIS Follow Up	71.25 units on a scale Standard Deviation 8.01
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
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
Test the Effect of tPBM on Impaired Decision Making BRIEF-A Baseline	41.75 units on a scale Standard Deviation 27.18
Test the Effect of tPBM on Impaired Decision Making BRIEF-A Day 5	58 units on a scale Standard Deviation 24.68
Test the Effect of tPBM on Impaired Decision Making BRIEF-A Follow Up	41.25 units on a scale Standard Deviation 24.53
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
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
Test the Effect of tPBM on Impaired Decision Making I-7 Impulsiveness Baseline	9.75 units on a scale Standard Deviation 5.31
Test the Effect of tPBM on Impaired Decision Making I-7 Impulsiveness Day 5	9 units on a scale Standard Deviation 4.08
Test the Effect of tPBM on Impaired Decision Making I-7 Impulsiveness Follow Up	8.25 units on a scale Standard Deviation 3.59
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
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
Test the Effect of tPBM on Impaired Decision Making I-7 Venturesomeness Baseline	6.5 units on a scale Standard Deviation 3.51
Test the Effect of tPBM on Impaired Decision Making I-7 Venturesomeness Day 5	6.25 units on a scale Standard Deviation 3.30
Test the Effect of tPBM on Impaired Decision Making I-7 Venturesomeness Follow Up	5.25 units on a scale Standard Deviation 3.77
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
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

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Transcranial Light Therapy Subjects n=4 Participants Subjects who passed screening and completed all study procedures. All subjects received a sham light therapy treatment followed by an active light therapy treatment at the first MRI session. This was a single-blind procedure.
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
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
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
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
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

Adverse Events

Subjects

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Subjects n=4 participants at risk Subjects who passed screening and completed all study procedures.
Skin and subcutaneous tissue disorders Skin Warming	75.0% 3/4 • Number of events 8 • 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. The Adverse Events Form captures any adverse event (serious or otherwise) that the subject experiences while participating in the study. Events may occur during or outside of study procedures. Subjects or staff could report Adverse Events. The event, severity, resolution, relatedness to treatment, action taken, and expectedness were all documented along with the start and end date (course) of the Adverse Event.
Skin and subcutaneous tissue disorders Skin Reddening Under Diode	75.0% 3/4 • Number of events 5 • 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. The Adverse Events Form captures any adverse event (serious or otherwise) that the subject experiences while participating in the study. Events may occur during or outside of study procedures. Subjects or staff could report Adverse Events. The event, severity, resolution, relatedness to treatment, action taken, and expectedness were all documented along with the start and end date (course) of the Adverse Event.
Infections and infestations Cold-like Virus/Common Cold	50.0% 2/4 • Number of events 2 • 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. The Adverse Events Form captures any adverse event (serious or otherwise) that the subject experiences while participating in the study. Events may occur during or outside of study procedures. Subjects or staff could report Adverse Events. The event, severity, resolution, relatedness to treatment, action taken, and expectedness were all documented along with the start and end date (course) of the Adverse Event.
Skin and subcutaneous tissue disorders Pimple on Forehead at Diode Location	25.0% 1/4 • Number of events 1 • 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. The Adverse Events Form captures any adverse event (serious or otherwise) that the subject experiences while participating in the study. Events may occur during or outside of study procedures. Subjects or staff could report Adverse Events. The event, severity, resolution, relatedness to treatment, action taken, and expectedness were all documented along with the start and end date (course) of the Adverse Event.
Psychiatric disorders Visual Illusion	25.0% 1/4 • Number of events 1 • 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. The Adverse Events Form captures any adverse event (serious or otherwise) that the subject experiences while participating in the study. Events may occur during or outside of study procedures. Subjects or staff could report Adverse Events. The event, severity, resolution, relatedness to treatment, action taken, and expectedness were all documented along with the start and end date (course) of the Adverse Event.

Additional Information

Dr. Paolo Cassano

Massachusetts General Hospital and Harvard Medical School

Phone: 617-643-9622

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place