Trial Outcomes & Findings for Transcranial Laser Therapy for Major Depressive Disorder (NCT NCT01538199)

Last Updated: 2017-11-29

Results Overview

We anticipate that TLT will decrease HAM-D17 scores in study subjects significantly more than Sham treatment. We expect that we will be also able to estimate the effect size of the antidepressant action of TLT. Analyses were done for all evaluable subjects (participants who met the a priori cut-off of a minimum of 4 t-PBM sessions for inclusion in the study analyses) and treatment completers (participants followed for the entire 8-week study period and who received a clinical assessment immediately after). HAM-D17 questions are rated on a scale of 0-4 or 0-2 (total score: 0-50) with higher scores indicating more severe pathology. Scores typically fall into the following ranges: not depressed = 0-7; mildly depressed = 8-13; moderately depressed = 14-18; severely depressed = 19-22; very severely depressed = 23 and over. For the pilot study, we analyzed subjects from Baseline to Week 8. A last observation carried forward (LOCF) was performed to account for one week 8n missing value.

Recruitment status

COMPLETED

Study phase

Target enrollment

28 participants

Primary outcome timeframe

Visit 1 (Baseline) and Visit 17 (Week 9); Pilot Phase: Visit 1 (Baseline) and Week 8

Results posted on

2017-11-29

Participant Flow

Participants were recruited in 2012 for the pilot phase of the study. Participants were recruited from February 2014 through June 2015 via Craigslist advertisements and the general research phone line for the Depression Clinical and Research Program at Massachusetts General Hospital.

10 subjects from the pilot phase and 9 subjects from phase 2 screen failed (HAM-D scores below or above threshold, active substance abuse, exclusionary comorbid medical disorder, did not pass drug screen, just started psychotherapy). 6 participants dropped out after screen (time constraints, moving, LTFU). 1 subject had primary diagnosis of PTSD.

Participant milestones

Participant milestones
Measure	Pilot Study Treatment Group 1 The TLT group will receive 2 TLT treatments per week for 3 weeks followed by a cross-over phase (where no treatment is given), followed by 2 sham treatments per week for 3 weeks. (see protocol change 10/28/2014)	Pilot Study Treatment Group 2 The sham group will receive 2 sham treatments per week for 3 weeks followed by a cross-over phase (where no treatment is given), followed by 2 TLT treatments per week for 3 weeks. (see protocol change 10/28/2014)	TLT Treatment Group 1 (Active TLT Treatment) The TLT group will receive 2 near-infrared radiation via Transcranial LED Therapy (TLT) treatments per week for 8 weeks Near-infrared radiation via Transcranial LED Therapy: The subject will lie down comfortably on a exam bed . The sites of application of TLT (left and right forehead) will be inspected for any skin lesions (e.g. laceration or signs of inflammation) which would contraindicate the treatment. The subject will wear protective eyewear in the form of goggles or eye pads. The staff administering the TLT will be careful not to shine the light in or near the eyes of the subject. The two OLS devices will be secured in position with the use of a Hair Net. The delivery of the TLT is expected to last 20 min total (simultaneous application on the left and right forehead). The subject will be asked to rest for five minutes after the delivery of TLT. The skin at the sites of the application will be inspected again prior to dismissing the subject.	TLT Treatment Group 2 (Placebo) The sham group will receive 2 treatments of the sham device per week for 8 weeks Sham device: The sham device does not emit near-infrared radiation.
Overall Study STARTED	4	3	10	11
Overall Study COMPLETED	3	1	8	8
Overall Study NOT COMPLETED	1	2	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Pilot Study Treatment Group 1 The TLT group will receive 2 TLT treatments per week for 3 weeks followed by a cross-over phase (where no treatment is given), followed by 2 sham treatments per week for 3 weeks. (see protocol change 10/28/2014)	Pilot Study Treatment Group 2 The sham group will receive 2 sham treatments per week for 3 weeks followed by a cross-over phase (where no treatment is given), followed by 2 TLT treatments per week for 3 weeks. (see protocol change 10/28/2014)	TLT Treatment Group 1 (Active TLT Treatment) The TLT group will receive 2 near-infrared radiation via Transcranial LED Therapy (TLT) treatments per week for 8 weeks Near-infrared radiation via Transcranial LED Therapy: The subject will lie down comfortably on a exam bed . The sites of application of TLT (left and right forehead) will be inspected for any skin lesions (e.g. laceration or signs of inflammation) which would contraindicate the treatment. The subject will wear protective eyewear in the form of goggles or eye pads. The staff administering the TLT will be careful not to shine the light in or near the eyes of the subject. The two OLS devices will be secured in position with the use of a Hair Net. The delivery of the TLT is expected to last 20 min total (simultaneous application on the left and right forehead). The subject will be asked to rest for five minutes after the delivery of TLT. The skin at the sites of the application will be inspected again prior to dismissing the subject.	TLT Treatment Group 2 (Placebo) The sham group will receive 2 treatments of the sham device per week for 8 weeks Sham device: The sham device does not emit near-infrared radiation.
Overall Study Lost to Follow-up	1	0	1	2
Overall Study participant did not have time	0	2	1	0
Overall Study Lack of Efficacy	0	0	0	1

Baseline Characteristics

Transcranial Laser Therapy for Major Depressive Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TLT Treatment Group 1 n=10 Participants The TLT group will receive 2 near-infrared radiation via Transcranial LED Therapy (TLT) treatments per week for 8 weeks Near-infrared radiation via Transcranial LED Therapy: The subject will lie down comfortably on a exam bed . The sites of application of TLT (left and right forehead) will be inspected for any skin lesions (e.g. laceration or signs of inflammation) which would contraindicate the treatment. The subject will wear protective eyewear in the form of goggles or eye pads. The staff administering the TLT will be careful not to shine the light in or near the eyes of the subject. The two OLS devices will be secured in position with the use of a Hair Net. The delivery of the TLT is expected to last 20 min total (simultaneous application on the left and right forehead). The subject will be asked to rest for five minutes after the delivery of TLT. The skin at the sites of the application will be inspected again prior to dismissing the subject.	TLT Treatment Group 2 n=11 Participants The sham group will receive 2 treatments of the sham device per week for 8 weeks Sham device: The sham device does not emit near-infrared radiation.	Screen Fail/Not Randomized n=15 Participants 9 participants screen failed (3 had HAM-D scores that were below the threshold for study inclusion, 2 had bipolar disorder, 1 had active substance abuse, 1 had an exclusionary comorbid medical disorder, 1 did not pass drug screen, 1 was not depressed) . 5 participants decided not to participate after the screen (1 due to time commitment, 2 were no longer interested, 1 was moving away, and 1 was lost to follow up). 1 was discontinued by investigator pre randomization at Visit 1 because it was discovered at Visit 1 that the patient's primary diagnosis was PTSD (MDD was secondary). Additionally, the patient's trauma symptoms significantly interfered with their ability to complete the study tasks.	Pilot Study Treatment Group 1 n=4 Participants The TLT group will receive 2 TLT treatments per week for 3 weeks followed by a cross-over phase (where no treatment is given), followed by 2 sham treatments per week for 3 weeks. (see protocol change 10/28/2014)	Pilot Study Treatment Group 2 n=3 Participants The sham group will receive 2 sham treatments per week for 3 weeks followed by a cross-over phase (where no treatment is given), followed by 2 TLT treatments per week for 3 weeks. (see protocol change 10/28/2014)	Pilot Study Screen Fail/Not Randomized n=11 Participants 10 participants screen failed (5 had HAM-D scores that were above threshold for study inclusion criteria, 1 had too many failed trials in the current depressive episode, 1 had active substance abuse, 2 did not meet criteria for Major Depressive Disorder at the time of the screening visit, 1 had just started psychotherapy at the time of the screen). 1 participant dropped out pre-randomization due to time constraints. (see protocol change 10/28/2014)	Total n=54 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants	11 Participants n=7 Participants	15 Participants n=5 Participants	4 Participants n=4 Participants	3 Participants n=21 Participants	11 Participants n=10 Participants	54 Participants n=115 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Age, Continuous	45 years STANDARD_DEVIATION 12.8 • n=5 Participants	50.7 years STANDARD_DEVIATION 13.3 • n=7 Participants	49.9 years STANDARD_DEVIATION 10.8 • n=5 Participants	47 years STANDARD_DEVIATION 14 • n=4 Participants	47.7 years STANDARD_DEVIATION 13.5 • n=21 Participants	38.3 years STANDARD_DEVIATION 11.7 • n=10 Participants	46.4 years STANDARD_DEVIATION 12.7 • n=115 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants	8 Participants n=10 Participants	33 Participants n=115 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants	3 Participants n=4 Participants	0 Participants n=21 Participants	3 Participants n=10 Participants	21 Participants n=115 Participants
Region of Enrollment United States	10 participants n=5 Participants	11 participants n=7 Participants	15 participants n=5 Participants	4 participants n=4 Participants	3 participants n=21 Participants	11 participants n=10 Participants	54 participants n=115 Participants

PRIMARY outcome

Timeframe: Visit 1 (Baseline) and Visit 17 (Week 9); Pilot Phase: Visit 1 (Baseline) and Week 8

Population: 3 randomized subjects excluded from TLT analyses because they received \<4 t-PBM treatments. 2 study completers from Group 1(last visit out of window,started new treatment ),1 subject from Group 2(started therapy)excluded as completers in analyses. Pilot Study Treatment Group 2 excluded because there was no data(drop out, post screen ineligibility).

Outcome measures

Outcome measures
Measure	TLT Treatment Group 1 (Active TLT Treatment) n=9 Participants The TLT group will receive 2 near-infrared radiation via Transcranial LED Therapy (TLT) treatments per week for 8 weeks Near-infrared radiation via Transcranial LED Therapy: The subject will lie down comfortably on a exam bed . The sites of application of TLT (left and right forehead) will be inspected for any skin lesions (e.g. laceration or signs of inflammation) which would contraindicate the treatment. The subject will wear protective eyewear in the form of goggles or eye pads. The staff administering the TLT will be careful not to shine the light in or near the eyes of the subject. The two OLS devices will be secured in position with the use of a Hair Net. The delivery of the TLT is expected to last 20 min total (simultaneous application on the left and right forehead). The subject will be asked to rest for five minutes after the delivery of TLT. The skin at the sites of the application will be inspected again prior to dismissing the subject.	TLT Treatment Group 2 (Placebo) n=9 Participants The sham group will receive 2 treatments of the sham device per week for 8 weeks Sham device: The sham device does not emit near-infrared radiation.	TLT Treatment Group 1 (Active TLT Treatment) Completers n=6 Participants The TLT group will receive 2 near-infrared radiation via Transcranial LED Therapy (TLT) treatments per week for 8 weeks (completers only). Near-infrared radiation via Transcranial LED Therapy: The subject will lie down comfortably on a exam bed . The sites of application of TLT (left and right forehead) will be inspected for any skin lesions (e.g. laceration or signs of inflammation) which would contraindicate the treatment. The subject will wear protective eyewear in the form of goggles or eye pads. The staff administering the TLT will be careful not to shine the light in or near the eyes of the subject. The two OLS devices will be secured in position with the use of a Hair Net. The delivery of the TLT is expected to last 20 min total (simultaneous application on the left and right forehead). The subject will be asked to rest for five minutes after the delivery of TLT. The skin at the sites of the application will be inspected again prior to dismissing the subject.	TLT Treatment Group 2 (Placebo) Completers n=7 Participants The sham group will receive 2 treatments of the sham device per week for 8 weeks. This only includes those who were followed for the entire 8-week study period and who received a clinical assessment immediately after. Sham device: The sham device does not emit near-infrared radiation.	Pilot Study Treatment Group 1 n=4 Participants The TLT group will receive 2 TLT treatments per week for 3 weeks followed by a cross-over phase (where no treatment is given), followed by 2 sham treatments per week for 3 weeks. 1 participant was missing a final visit 8 value, so LOCF was used for this value. (see protocol change 10/28/2014)
Change in Hamilton Depression Rating Scale (HAM-D 17) Score	-11.7 units on a scale Standard Deviation 7.47	-5.3 units on a scale Standard Deviation 7.03	-15.7 units on a scale Standard Deviation 4.41	-6.1 units on a scale Standard Deviation 7.86	-6.75 units on a scale Standard Deviation 4.85

SECONDARY outcome

Timeframe: Assessed at odd-numbered Visits 1-17. The single value to be analyzed is the number of distinct side effects that occurred at least once during these assessment visits for each subject.

Population: 3 subjects excluded from TLT because they received \<4 t-PBM treatments.1 excluded from Group 1 due to unreliable reporting.1 Group 1 and 1 Group 2 excluded due to no final visit score.1 excluded from Pilot Study Treatment Group 1 due to no final visit score.Pilot Study Treatment Group 2 excluded due to no data(drop out, post screen ineligibility).

To assess the safety and tolerability of TLT in depressed subjects: We predict that TLT will be safe and well-tolerated, as assessed by the SAFTEE-SI. We anticipate no significant differences between TLT and Sham in side-effects.The SAFTEE is a commonly used instrument developed by the NIMH and adapted into a self-report instrument. The version we used is the same used by the NIMH-sponsored CO-MED trial. It examines all possible treatment-emergent side effects and adverse symptoms, including suicidal thoughts and behaviors, and self-injurious behavior. The SAFTEE analyses are ongoing and will be reported in a second paper (they are not included in the primary outcomes paper). The single value analyzed is the total number of distinct treatment-emergent side-effects (a side effect is defined as any item on the SAFTEE for which severity increased by two or more levels from baseline to any visit) that occurred for each subject. Range: 0 to 165; higher values represent worse outcomes.

Outcome measures

Outcome measures
Measure	TLT Treatment Group 1 (Active TLT Treatment) n=7 Participants The TLT group will receive 2 near-infrared radiation via Transcranial LED Therapy (TLT) treatments per week for 8 weeks Near-infrared radiation via Transcranial LED Therapy: The subject will lie down comfortably on a exam bed . The sites of application of TLT (left and right forehead) will be inspected for any skin lesions (e.g. laceration or signs of inflammation) which would contraindicate the treatment. The subject will wear protective eyewear in the form of goggles or eye pads. The staff administering the TLT will be careful not to shine the light in or near the eyes of the subject. The two OLS devices will be secured in position with the use of a Hair Net. The delivery of the TLT is expected to last 20 min total (simultaneous application on the left and right forehead). The subject will be asked to rest for five minutes after the delivery of TLT. The skin at the sites of the application will be inspected again prior to dismissing the subject.	TLT Treatment Group 2 (Placebo) n=8 Participants The sham group will receive 2 treatments of the sham device per week for 8 weeks Sham device: The sham device does not emit near-infrared radiation.	TLT Treatment Group 1 (Active TLT Treatment) Completers n=3 Participants The TLT group will receive 2 near-infrared radiation via Transcranial LED Therapy (TLT) treatments per week for 8 weeks (completers only). Near-infrared radiation via Transcranial LED Therapy: The subject will lie down comfortably on a exam bed . The sites of application of TLT (left and right forehead) will be inspected for any skin lesions (e.g. laceration or signs of inflammation) which would contraindicate the treatment. The subject will wear protective eyewear in the form of goggles or eye pads. The staff administering the TLT will be careful not to shine the light in or near the eyes of the subject. The two OLS devices will be secured in position with the use of a Hair Net. The delivery of the TLT is expected to last 20 min total (simultaneous application on the left and right forehead). The subject will be asked to rest for five minutes after the delivery of TLT. The skin at the sites of the application will be inspected again prior to dismissing the subject.	TLT Treatment Group 2 (Placebo) Completers The sham group will receive 2 treatments of the sham device per week for 8 weeks. This only includes those who were followed for the entire 8-week study period and who received a clinical assessment immediately after. Sham device: The sham device does not emit near-infrared radiation.	Pilot Study Treatment Group 1 The TLT group will receive 2 TLT treatments per week for 3 weeks followed by a cross-over phase (where no treatment is given), followed by 2 sham treatments per week for 3 weeks. 1 participant was missing a final visit 8 value, so LOCF was used for this value. (see protocol change 10/28/2014)
Systematic Assessment for Treatment Emergent Events-systematic Inquiry (SAFTEE-SI)	-17 units on a scale Standard Deviation 12.60	-9.38 units on a scale Standard Deviation 20.33	-10.33 units on a scale Standard Deviation 13.48	—	—

SECONDARY outcome

Timeframe: Visits 1, 3, 5, 7, 9, 11, 13, 15, and 17

Population: 3 randomized subjects excluded from TLT analyses because they received \<4 t-PBM treatments.

To assess the safety and tolerability of the TLT in depressed subjects: We predict that the TLT will be safe and well-tolerated by depressed patients, as assessed by the following rating scales: ADVERSE EVENTS FORM. We anticipate no significant differences in between TLT and Sham treatment as concerns side-effects. Due to the small sample size and the variability of reported adverse events, we decided that descriptive reporting (i.e. reporting each subject's adverse events individually) was more appropriate than analysis. All adverse events were reported in the adverse events section. In the outcome measure data table below we report the number of participants in each group who experienced an adverse event.

Outcome measures

Outcome measures
Measure	TLT Treatment Group 1 (Active TLT Treatment) n=9 Participants The TLT group will receive 2 near-infrared radiation via Transcranial LED Therapy (TLT) treatments per week for 8 weeks Near-infrared radiation via Transcranial LED Therapy: The subject will lie down comfortably on a exam bed . The sites of application of TLT (left and right forehead) will be inspected for any skin lesions (e.g. laceration or signs of inflammation) which would contraindicate the treatment. The subject will wear protective eyewear in the form of goggles or eye pads. The staff administering the TLT will be careful not to shine the light in or near the eyes of the subject. The two OLS devices will be secured in position with the use of a Hair Net. The delivery of the TLT is expected to last 20 min total (simultaneous application on the left and right forehead). The subject will be asked to rest for five minutes after the delivery of TLT. The skin at the sites of the application will be inspected again prior to dismissing the subject.	TLT Treatment Group 2 (Placebo) n=9 Participants The sham group will receive 2 treatments of the sham device per week for 8 weeks Sham device: The sham device does not emit near-infrared radiation.	TLT Treatment Group 1 (Active TLT Treatment) Completers n=4 Participants The TLT group will receive 2 near-infrared radiation via Transcranial LED Therapy (TLT) treatments per week for 8 weeks (completers only). Near-infrared radiation via Transcranial LED Therapy: The subject will lie down comfortably on a exam bed . The sites of application of TLT (left and right forehead) will be inspected for any skin lesions (e.g. laceration or signs of inflammation) which would contraindicate the treatment. The subject will wear protective eyewear in the form of goggles or eye pads. The staff administering the TLT will be careful not to shine the light in or near the eyes of the subject. The two OLS devices will be secured in position with the use of a Hair Net. The delivery of the TLT is expected to last 20 min total (simultaneous application on the left and right forehead). The subject will be asked to rest for five minutes after the delivery of TLT. The skin at the sites of the application will be inspected again prior to dismissing the subject.	TLT Treatment Group 2 (Placebo) Completers n=3 Participants The sham group will receive 2 treatments of the sham device per week for 8 weeks. This only includes those who were followed for the entire 8-week study period and who received a clinical assessment immediately after. Sham device: The sham device does not emit near-infrared radiation.	Pilot Study Treatment Group 1 The TLT group will receive 2 TLT treatments per week for 3 weeks followed by a cross-over phase (where no treatment is given), followed by 2 sham treatments per week for 3 weeks. 1 participant was missing a final visit 8 value, so LOCF was used for this value. (see protocol change 10/28/2014)
Number of Participants With Adverse Events	7 Participants	2 Participants	1 Participants	1 Participants	—

POST_HOC outcome

Timeframe: Visit 1 (Baseline) and Visit 17 (Week 9)

Population: Excluded: 3 randomized subjects who had \<4 t-PBM treatments; 1 from Group 1 (unreliable reporting); 2 from Group 1 (started new treatment),1 from Group 2 (started therapy). 1 from Pilot study group 1 (no final visit). Pilot Study Group 2 excluded because there was no data (2 subjects dropped out, 1 subject ineligible--see Participant Flow).

This is a brief (16-item) self-report inventory of core depressive symptoms such as sleep, depressed mood, appetite, concentration, suicidal ideation, interest, energy, psychomotor retardation or agitation. QIDS scores range from 0-27. Severity of depression can be judged based on the total score: 1-5 = No depression, 6-10 = Mild depression, 11-15 = Moderate depression. 16-20 = Severe depression, 21-27 = Very severe depression. Analyses were done for all evaluable subjects (participants who met the a priori cut-off of a minimum of four t-PBM sessions for inclusion in the study analyses) and treatment completers (participants who were followed for the entire 8-week study period and who received a clinical assessment immediately after). Pilot Study Group 2 excluded because no analyses were completed for this group (see participant flow)

Outcome measures

Outcome measures
Measure	TLT Treatment Group 1 (Active TLT Treatment) n=8 Participants The TLT group will receive 2 near-infrared radiation via Transcranial LED Therapy (TLT) treatments per week for 8 weeks Near-infrared radiation via Transcranial LED Therapy: The subject will lie down comfortably on a exam bed . The sites of application of TLT (left and right forehead) will be inspected for any skin lesions (e.g. laceration or signs of inflammation) which would contraindicate the treatment. The subject will wear protective eyewear in the form of goggles or eye pads. The staff administering the TLT will be careful not to shine the light in or near the eyes of the subject. The two OLS devices will be secured in position with the use of a Hair Net. The delivery of the TLT is expected to last 20 min total (simultaneous application on the left and right forehead). The subject will be asked to rest for five minutes after the delivery of TLT. The skin at the sites of the application will be inspected again prior to dismissing the subject.	TLT Treatment Group 2 (Placebo) n=9 Participants The sham group will receive 2 treatments of the sham device per week for 8 weeks Sham device: The sham device does not emit near-infrared radiation.	TLT Treatment Group 1 (Active TLT Treatment) Completers n=5 Participants The TLT group will receive 2 near-infrared radiation via Transcranial LED Therapy (TLT) treatments per week for 8 weeks (completers only). Near-infrared radiation via Transcranial LED Therapy: The subject will lie down comfortably on a exam bed . The sites of application of TLT (left and right forehead) will be inspected for any skin lesions (e.g. laceration or signs of inflammation) which would contraindicate the treatment. The subject will wear protective eyewear in the form of goggles or eye pads. The staff administering the TLT will be careful not to shine the light in or near the eyes of the subject. The two OLS devices will be secured in position with the use of a Hair Net. The delivery of the TLT is expected to last 20 min total (simultaneous application on the left and right forehead). The subject will be asked to rest for five minutes after the delivery of TLT. The skin at the sites of the application will be inspected again prior to dismissing the subject.	TLT Treatment Group 2 (Placebo) Completers n=7 Participants The sham group will receive 2 treatments of the sham device per week for 8 weeks. This only includes those who were followed for the entire 8-week study period and who received a clinical assessment immediately after. Sham device: The sham device does not emit near-infrared radiation.	Pilot Study Treatment Group 1 n=3 Participants The TLT group will receive 2 TLT treatments per week for 3 weeks followed by a cross-over phase (where no treatment is given), followed by 2 sham treatments per week for 3 weeks. 1 participant was missing a final visit 8 value, so LOCF was used for this value. (see protocol change 10/28/2014)
Change in Quick Inventory of Depressive Symptomatology-Self Rated Scale (QIDS-SR) Score	-5.9 units on a scale Standard Deviation 6.29	-3.7 units on a scale Standard Deviation 2.91	-9.8 units on a scale Standard Deviation 4.09	-4.3 units on a scale Standard Deviation 3.04	-2.33 units on a scale Standard Deviation 4.22

Adverse Events

TLT Treatment Group 1

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

TLT Treatment Group 2

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Pilot Study Treatment Group 1

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Pilot Study Treatment Group 2

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Paolo Cassano

Massachusetts General Hospital

Phone: 617-643-9622

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	TLT Treatment Group 1 n=10 participants at risk The TLT group will receive 2 near-infrared radiation via Transcranial LED Therapy (TLT) treatments per week for 8 weeks Near-infrared radiation via Transcranial LED Therapy: The subject will lie down comfortably on a exam bed . The sites of application of TLT (left and right forehead) will be inspected for any skin lesions (e.g. laceration or signs of inflammation) which would contraindicate the treatment. The subject will wear protective eyewear in the form of goggles or eye pads. The staff administering the TLT will be careful not to shine the light in or near the eyes of the subject. The two OLS devices will be secured in position with the use of a Hair Net. The delivery of the TLT is expected to last 20 min total (simultaneous application on the left and right forehead). The subject will be asked to rest for five minutes after the delivery of TLT. The skin at the sites of the application will be inspected again prior to dismissing the subject.	TLT Treatment Group 2 n=11 participants at risk The sham group will receive 2 treatments of the sham device per week for 8 weeks Sham device: The sham device does not emit near-infrared radiation.	Pilot Study Treatment Group 1 n=4 participants at risk The TLT group will receive 2 TLT treatments per week for 3 weeks followed by a cross-over phase (where no treatment is given), followed by 2 sham treatments per week for 3 weeks. (see protocol change 10/28/2014)	Pilot Study Treatment Group 2 n=3 participants at risk The sham group will receive 2 sham treatments per week for 3 weeks followed by a cross-over phase (where no treatment is given), followed by 2 TLT treatments per week for 3 weeks. (see protocol change 10/28/2014)
Gastrointestinal disorders gastro-intestinal sickness	10.0% 1/10 • Number of events 1 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/11 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	25.0% 1/4 • Number of events 1 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/3 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).
General disorders restless sleep	10.0% 1/10 • Number of events 1 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/11 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/4 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/3 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).
General disorders headaches	10.0% 1/10 • Number of events 1 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	9.1% 1/11 • Number of events 1 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/4 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/3 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).
General disorders taste illusion	10.0% 1/10 • Number of events 1 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/11 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/4 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/3 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).
Gastrointestinal disorders abdominal bloating	10.0% 1/10 • Number of events 1 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/11 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/4 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/3 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).
General disorders gout	10.0% 1/10 • Number of events 1 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/11 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/4 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/3 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).
Psychiatric disorders self-harm	10.0% 1/10 • Number of events 1 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/11 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/4 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/3 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).
General disorders insomnia	20.0% 2/10 • Number of events 2 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	9.1% 1/11 • Number of events 1 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/4 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/3 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).
General disorders Irritability	20.0% 2/10 • Number of events 3 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/11 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/4 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/3 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).
General disorders visual illusions (vivid colors)	20.0% 2/10 • Number of events 2 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/11 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/4 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/3 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).
General disorders decreased memory; word finding difficulties	10.0% 1/10 • Number of events 1 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/11 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/4 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/3 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).
General disorders left torso pain	0.00% 0/10 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	9.1% 1/11 • Number of events 1 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/4 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/3 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).
General disorders belching	0.00% 0/10 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	9.1% 1/11 • Number of events 1 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/4 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/3 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).
General disorders pressure/pain on back of head during 4T Scan	0.00% 0/10 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/11 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/4 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	33.3% 1/3 • Number of events 1 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).
General disorders dizziness/tingling sensation in head	0.00% 0/10 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/11 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	0.00% 0/4 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).	33.3% 1/3 • Number of events 1 • Adverse events were collected for the duration of the study. Study clinicians inquired about any adverse events once a week for all 8 weeks of treatment. Clinicians also asked about adverse events at Visit 17 (follow up visit after the 8 week treatment).