Bipolar DisorderPhase 2TPEBNCT05408637

Transcranial Photobiomodulation for Executive Function in Bipolar Disorder

A Phase 2 study testing Transcranial Phoobiomodulation (tPBM) in people with Bipolar Disorder, run by Paolo Cassano at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Bipolar Disorder
What is being tested?: Transcranial Phoobiomodulation (tPBM)
Type of treatment: Medical device
How many people: 13 participants
Where: 1 siteUnited States
Study dates: 9 Aug 2022to 14 May 2024
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 10Show fewer

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Mass General Hospital Navy Yard Building 149
Charlestown, Massachusetts, 02129

Other trials in United States

About this study

Official title: Transcranial Photobiomodulation for Executive Function in Bipolar Disorder (TPEB)

Read the 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.

Conditions: Bipolar Disorder
Being tested: Transcranial Phoobiomodulation (tPBM)
Keywords: Bipolar, Bipolar Disorder
Medical subject headings: Bipolar Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Transcranial Phoobiomodulation (tPBM)Device
Also called Transcranial Light Therapy, Low Level Laser-Light Therapy
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.

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: Day 1 and Day 5

Secondary outcomes (2)

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.
Measured: 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.
Measured: Baseline to Follow Up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

9 Aug 202214 May 2024

First posted7 Jun 2022
Study start9 Aug 2022
Primary completion14 May 2024
Study completion14 May 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Bipolar DisorderStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: All participants will receive five active tPBM treatments and one sham tPBM treatment.
Masking: Single blind
Who is masked: Participant
Enrolment: 13 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05408637
Sponsor's protocol ID: 2022p000289
Acronym: TPEB
Status last verified: Aug 2025
First submitted: 17 May 2022
Last updated: 28 Aug 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: Yes
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Bipolar Disorder trials

Study at a glance

From the registry record, last updated by the sponsor on 28 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Transcranial Photobiomodulation for Executive Function in Bipolar Disorder (TPEB)
ClinicalTrials.gov ID: NCT05408637
Acronym / sponsor ID: TPEB / 2022p000289
Conditions: Bipolar Disorder
Keywords: Bipolar, Bipolar Disorder
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 13 participants (actual)
Lead sponsor: Paolo CassanoUniversity, hospital or other
Study start: 9 Aug 2022 (actual)
Primary completion: 14 May 2024 (actual)
Study completion: 14 May 2024 (actual)
First posted: 7 Jun 2022 (actual)
Results: Posted 28 Aug 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: Single blind (participant)
Model description: All participants will receive five active tPBM treatments and one sham tPBM treatment.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (10 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Transcranial Phoobiomodulation (tPBM)Also: Transcranial Light Therapy, Low Level Laser-Light TherapyTranscranial 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.	Device	–

Primary outcome

Test the Effect of Transcranial Photobiomodulation (tPBM) on Cerebral Blood Flow (CBF)
Time frame: 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
Time frame: 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.

2 secondary outcomes

Test the Effect of tPBM on Impaired Decision Making
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)
Time frame: Baseline to Follow Up

Results and safety

Results posted to the registry on 28 Aug 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Transcranial Light Therapy	4	4

Primary outcome: Test the Effect of Transcranial Photobiomodulation (tPBM) on Cerebral Blood Flow (CBF)

Time frame: Day 1 of tPBM Treatment. Mean (Standard Deviation). Unit: A.U.

Measure	Transcranial Light Therapy Subjects n = 4
Sham Stimulation BOLD Signal	6611.645 (794.5616)
Active Stimulation BOLD Signal	6666.398 (784.01)

Transcranial Light Therapy Subjects: Mean Difference (Final Values): 54.75
Transcranial Light Therapy Subjects: Percent Difference: 0.85
Transcranial Light Therapy Subjects: Cohen's d: 0.07

Primary outcome: Test Effect of tPBM on CBF

Time frame: Day 1 and Day 5. Mean (Standard Deviation). Unit: A.U.

Measure	Transcranial Light Therapy Subjects n = 4
Day 1 Active BOLD Signal	6666.398 (784.01)
Day 5 Active BOLD Signal	6891.237 (412.7808)

Transcranial Light Therapy Subjects: Mean Difference (Final Values): 224.8392
Transcranial Light Therapy Subjects: Percent Difference: 4.35
Transcranial Light Therapy Subjects: Cohen's d: 0.36

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Subjects	0 of 4 (0%)	3 of 4 (75%)	0 of 4

Limitations and caveats (from the sponsor): The sample size is small, limiting statistical analyses and interpretation. The results highlight the need for group-level statistical analyses in a larger sample to validate. The inter-individual variability suggests that future studies should include additional longitudinal tracking and more examination of moderating factors.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Bipolar Disorder

Not yet recruitingObservational study
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Mood Disorders, Major Depressive Diorder
RecruitingObservational study
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Transcranial Phoobiomodulation (tPBM) in people with Bipolar Disorder, run by Paolo Cassano at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Test the Effect of Transcranial Photobiomodulation (tPBM) on Cerebral Blood Flow (CBF) (time frame: Day 1 of tPBM Treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05408637.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2025.