Transcranial Laser Therapy, Continuous and Pulsed Light, for Major Depressive Disorder (ELATED-3) (ELATED-3)

• ClinicalTrials.gov Identifier: NCT02959307
• Recruitment Status: Completed
• First Posted: November 9, 2016
• Results First Posted: September 21, 2020
• Last Update Posted: September 21, 2020
• Sponsor: Massachusetts General Hospital
• Collaborator: LiteCure LLC
• Information provided by (Responsible Party): Paolo Cassano, Massachusetts General Hospital

Tracking Information

• First Submitted Date: November 7, 2016
• First Posted Date: November 9, 2016
• Results First Submitted Date: June 16, 2020
• Results First Posted Date: September 21, 2020
• Last Update Posted Date: September 21, 2020
• Study Start Date: November 2016
• Actual Primary Completion Date: November 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 31, 2020)

• Quick Inventory of Depressive Symptomatology-Phase 1 [ Time Frame: 6 weeks - Sequential-parallel comparison design ]
  This is a brief (16-item) clinician-rated inventory of core depressive symptoms such as sleep, depressed mood, appetite, concentration, suicidal ideation, interest, energy, psychomotor retardation or agitation. Scores range from 0-27, higher scores indicating greater depression severity.
• Quick Inventory of Depressive Symptomatology(QIDS)-Phase 2 [ Time Frame: 6 weeks - Sequential-parallel comparison design ]
  This is a brief (16-item) clinician-rated inventory of core depressive symptoms such as sleep, depressed mood, appetite, concentration, suicidal ideation, interest, energy, psychomotor retardation or agitation. Scores range from 0-27, higher scores indicating greater depression severity.

Original Primary Outcome Measures (submitted: November 7, 2016)

Quick Inventory of Depressive Symptomatology (QIDS-C) [ Time Frame: 6 weeks - SPCD design ]

This is a brief (16-item) clinician-rated inventory of core depressive symptoms such as sleep, depressed mood, appetite, concentration, suicidal ideation, interest, energy, psychomotor retardation or agitation.

Current Secondary Outcome Measures (submitted: August 31, 2020)

• Hamilton Depression Rating Scale - 17 Items(Phase 1) [ Time Frame: 6 weeks - Sequential-parallel comparison design ]
  assessment of the patient's depressive symptoms, using a structured interview and defined anchor points. The Hamilton Depression Rating Scale aims to quantify the degree of depression in patients who already have a diagnosis of major depression. Score ranges from 0-52. Higher score indicates greater severity of depression.
• Hamilton Depression Rating Scale - 17 Items(Phase 2) [ Time Frame: 6 weeks - Sequential-parallel comparison design ]
  assessment of the patient's depressive symptoms, using a structured interview and defined anchor points. The Hamilton Depression Rating Scale aims to quantify the degree of depression in patients who already have a diagnosis of major depression. Score ranges from 0-52. Higher score indicates greater severity of depression.

Original Secondary Outcome Measures (submitted: November 7, 2016)

• Pattern Separation Task [ Time Frame: 6 week - SPCD design ]
  The pattern separation task is a high throughput behavioral task that captures the input-output transformation function characteristic of pattern separation processes
• Multi-Source Interference Task [ Time Frame: 6 week - SPCD design ]
  The Multi-Source Interference Task (MSIT) is a cognitive paradigm that was designed to reliably identify the cingulo-frontal-parietal cognitive/attention network (CFP network) within individual subjects
• Hamilton Depression Rating Scale - 17 items [ Time Frame: 6 weeks - SPCD design ]
  assessment of the patient's depressive symptoms, using a structured interview and defined anchor points. The HAM-D aims to quantify the degree of depression in patients who already have a diagnosis of major depression.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Transcranial Laser Therapy, Continuous and Pulsed Light, for Major Depressive Disorder (ELATED-3)
• Official Title: Transcranial Continuous and Pulse Near-Infrared Light in Depression: a Placebo-Controlled Study (ELATED-3).
• Brief Summary: Transcranial Light Therapy involves non-invasive and invisible beams of light that increase energy metabolism in the brain. Transcranial light therapy has been found to promote brain metabolism which may help people with depression. The research team proposes a novel approach to treating depression by using transcranial light therapy.

Detailed Description

During study visits a clinician applies transcranial light therapy to both sides of a participant's forehead for about 30 minutes. The study involves, 1 screening visit which may last up to the 3 hours, 24 transcranial light therapy treatment visits, and 1 post-treatment visit (26 total visits to the Massachusetts General Hospital).

If a participant qualifies for the study, we assign the participant by chance to receive either active transcranial light therapy or sham transcranial light therapy treatment. During sham transcranial light therapy visits, the transcranial light therapy device will not produce near infrared waves (e.g., light energy that cannot penetrate the skin and cranium). Participants have an equal chance of being assigned to the active transcranial light therapy or the sham transcranial light therapy when first randomized. Neither the participant, nor the clinician, nor any research staff will know which study group the participant belongs.

Participants are randomized a second time after 6-weeks in the study. If the participant were in the sham group the first 6-weeks, that participant may receive the active transcranial light therapy treatment after re-randomization. If the participant were already in the active transcranial light therapy group during the first 6-weeks the participant continues receiving the active treatment. All in all, participants have a 1 in 3 chance of receiving the active transcranial light therapy treatment at some point during the study.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Depression
• Major Depressive Disorder

Intervention

• Device: Transcranial 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.
  Other Name: Low Level Laser-Light Therapy, Photobiomodulation
• Device: Sham Transcranial Light Therapy
  The same device used for the actual transcranial light therapy is used as the sham device; The device, when set to sham, will mimic the actual transcranial light therapy; however, when set to sham the device does not emit skin and cranium penetrating light emitting diode light energy.
  Other Name: Placebo

Study Arms

• Experimental: Transcranial Light Therapy
  Transcranial light therapy penetrates the skin and brain using light energy and, the light energy may activate under-stimulated brain regions.
  Intervention: Device: Transcranial Light Therapy
• Sham Comparator: Sham Transcranial Light Therapy
  For the sham group, The transcranial light therapy device uses nonpenetrating light emitting diode light energy. The sham controls for which participants improve from the actual transcranial light therapy treatment and which participants improve during the study for reasons other than the therapy
  Interventions:

  • Device: Transcranial Light Therapy
  • Device: Sham Transcranial Light Therapy

• Publications *: Iosifescu DV, Norton RJ, Tural U, Mischoulon D, Collins K, McDonald E, De Taboada L, Foster S, Cusin C, Yeung A, Clain A, Schoenfeld D, Hamblin MR, Cassano P. Very Low-Level Transcranial Photobiomodulation for Major Depressive Disorder: The ELATED-3 Multicenter, Randomized, Sham-Controlled Trial. J Clin Psychiatry. 2022 Aug 8;83(5):21m14226. doi: 10.4088/JCP.21m14226.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 31, 2020): 49
• Original Estimated Enrollment (submitted: November 7, 2016): 50
• Actual Study Completion Date: November 2018
• Actual Primary Completion Date: November 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participant age at screening will be between (>=)18 and 70 years old (inclusive).
• Participant meets the criteria for major depressive disorder
• Participants informed consent obtained in writing
• Participant is available to participate in the study for at least 12 weeks

Exclusion Criteria:

• Significant skin conditions near the application site
• Any use of light-activated drugs (photodynamic therapy) within 14 days prior to study enrollment
• Recent history of stroke
• The participant failed more than 2 adequate treatment with Federal Drug Administration approved antidepressants during current episode per antidepressant treatment response questionnaire criteria (less than 50% decrease in depressive symptomatology).
• Structured psychotherapy focused on treating the subject's depression (i.e. cognitive behavioral therapy or interpersonal therapy) is permitted if started at least 8 weeks prior to the screening visit.
• Substance dependence or abuse in the past 3 months.
• History of a psychotic disorder or psychotic episode (current psychotic episode per M.I.N.I neuro-psychiatric assessment).
• Bipolar affective disorder (per M.I.N.I neuro-psychiatric assessment).
• Unstable medical illness, defined as any medical illness which is not well-controlled with standard-of-care medications (e.g., insulin for diabetes mellitus, hydrochlorothiazide for hypertension).
• Active suicidal or homicidal ideation (both intention and plan are present), as determined by Columbia Suicide Severity Rating Scale
• Cognitive impairment (Montreal Cognitive Assessment <21)
• The participant has a significant skin condition (i.e., hemangioma, scleroderma, psoriasis, rash, open wound or tattoo) on the subject's scalp that is found to be in proximity to any of the procedure sites.
• The subject has an implant of any kind in the head (e.g. stent, clipped aneurysm, embolised arteriovenous malformation, implantable shunt - Hakim valve).
• Any use of light-activated drugs (photodynamic therapy) within 14 days prior to study enrollment (in US: Visudyne (verteporfin) - for age related macular degeneration; Aminolevulinic Acid- for actinic keratoses; Photofrin (porfimer sodium) - for esophageal cancer, non-small cell lung cancer; Levulan Kerastick (aminolevulinic acid hydrogen chloride) - for actinic keratosis; 5-aminolevulinic acid for non-melanoma skin cancer)
• Women of child-bearing potential must use a double-barrier method for birth control (e.g. condoms plus spermicide) if sexually active.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02959307
• Other Study ID Numbers: 2016P001490
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Personally unidentifiable information will be sent to Dr. Anastasia Ivanova, a privately contracted biostatistician form Chapel Hill North Carolina, for analyses. All information sent to Dr. Ivanova uses acrostics in place of personally identifiable information.

• Current Responsible Party: Paolo Cassano, Massachusetts General Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Massachusetts General Hospital
• Original Study Sponsor: Same as current
• Collaborators: LiteCure LLC

Investigators

• Principal Investigator: Paolo Cassano, M.D.; Depression Clinical and Research Program

• PRS Account: Massachusetts General Hospital
• Verification Date: August 2020