Transcranial Near Infrared Radiation and Cerebral Blood Flow in Depression

NCT04366258 | Completed Results DMC FDA Device

• 2 other identifiers: 20-002171R61MH122647-01
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 3

Brief Summary

This study will compare the effect of three transcranial photobiomodulation (t-PBM) doses (high, middle, and low irradiance) to sham t-PBM on PFC CBF as assessed with fMRI (BOLD) in this multi-center, phase I, double-blinded, dose-ranging, controlled, crossover study of 30 subjects with MDD. All eligible participants will undergo four sessions of t-PBM during fMRI so that they experience irradiances of 50, 300 and 700 mW/cm2 as well as sham. The order of dose administration will be randomized and t-PBM will be administered with the LightForce® EXPi Deep Tissue Laser TherapyTM System, Transcranial PhotoBioModulation-1000 (tPBM-2.0).

Conditions

Major Depressive Disorder

Keywords

MDD, neuromodulation, transcranial photobiomodulation

Outcome Measures

Primary Outcomes (4)

• Percentage Change in Prefrontal Cortex (PFC) Cerebral Blood Flow (CBF) During High-Irradiance t-PBM

  CBF is measured as Blood Oxygen Level Dependent (BOLD) signal on functional magnetic resonance imaging (fMRI). BOLD signal reflects changes in regional CBF that delineate regional activity. A positive BOLD signal marks an increase in regional blood flow, while a negative BOLD signal marks a decrease in regional blood flow. A positive percent change indicates that blood flow increased in the region of interest between scans, a negative percent change indicates blood flow decreased between scans. Approximately 60 minutes of fMRI data are recorded in the left and right dorsolateral prefrontal cortical regions of interest at each transcranial photobiomodulation (t-PBM) treatment visit, including: approximately 20 minutes prior to t-PBM administration, approximately 20 minutes coinciding with t-PBM administration, and approximately 20 minutes following t-PBM administration.

  20 Minutes Pre-Intervention, 20 Minutes Post-Intervention (Total duration: 60 min); Up to Week 7

• Percentage Change in Prefrontal Cortex (PFC) Cerebral Blood Flow (CBF) During Middle-Irradiance t-PBM

  CBF is measured as Blood Oxygen Level Dependent (BOLD) signal on functional magnetic resonance imaging (fMRI). BOLD signal reflects changes in regional CBF that delineate regional activity. A positive BOLD signal marks an increase in regional blood flow, while a negative BOLD signal marks a decrease in regional blood flow. A positive percent change indicates that blood flow increased in the region of interest between scans, a negative percent change indicates blood flow decreased between scans. Approximately 60 minutes of fMRI data are recorded in the left and right dorsolateral prefrontal cortical regions of interest at each transcranial photobiomodulation (t-PBM) treatment visit, including: approximately 20 minutes prior to t-PBM administration, approximately 20 minutes coinciding with t-PBM administration, and approximately 20 minutes following t-PBM administration.

  20 Minutes Pre-Intervention, 20 Minutes Post-Intervention (Total duration: 60 min); Up to Week 7

• Percentage Change in Prefrontal Cortex (PFC) Cerebral Blood Flow (CBF) During Low-Irradiance t-PBM

  CBF is measured as Blood Oxygen Level Dependent (BOLD) signal on functional magnetic resonance imaging (fMRI). BOLD signal reflects changes in regional CBF that delineate regional activity. A positive BOLD signal marks an increase in regional blood flow, while a negative BOLD signal marks a decrease in regional blood flow. A positive percent change indicates that blood flow increased in the region of interest between scans, a negative percent change indicates blood flow decreased between scans. Approximately 60 minutes of fMRI data are recorded in the left and right dorsolateral prefrontal cortical regions of interest at each transcranial photobiomodulation (t-PBM) treatment visit, including: approximately 20 minutes prior to t-PBM administration, approximately 20 minutes coinciding with t-PBM administration, and approximately 20 minutes following t-PBM administration.

  20 Minutes Pre-Intervention, 20 Minutes Post-Intervention (Total duration: 60 min); Up to Week 7

• Percentage Change in Prefrontal Cortex (PFC) Cerebral Blood Flow (CBF) During Sham Treatment

  CBF is measured as Blood Oxygen Level Dependent (BOLD) signal on functional magnetic resonance imaging (fMRI). BOLD signal reflects changes in regional CBF that delineate regional activity. A positive BOLD signal marks an increase in regional blood flow, while a negative BOLD signal marks a decrease in regional blood flow. A positive percent change indicates that blood flow increased in the region of interest between scans, a negative percent change indicates blood flow decreased between scans. Approximately 60 minutes of fMRI data are recorded in the left and right dorsolateral prefrontal cortical regions of interest at each transcranial photobiomodulation (t-PBM) treatment visit, including: approximately 20 minutes prior to t-PBM administration, approximately 20 minutes coinciding with t-PBM administration, and approximately 20 minutes following t-PBM administration.

  20 Minutes Pre-Intervention, 20 Minutes Post-Intervention (Total duration: 60 min); Up to Week 7

Secondary Outcomes (14)

• Change in Brain Temperature During High-Irradiance t-PBM

  Immediately Pre-Intervention, Immediately Post-Intervention; Up to Week 7

• Change in Brain Temperature During Middle-Irradiance t-PBM

  Immediately Pre-Intervention, Immediately Post-Intervention; Up to Week 7

• Change in Brain Temperature During Low-Irradiance t-PBM

  Immediately Pre-Intervention, Immediately Post-Intervention; Up to Week 7

• Change in Brain Temperature During Sham Treatment

  Immediately Pre-Intervention, Immediately Post-Intervention; Up to Week 7

• Change in Columbia Suicide Severity Rating Scale (C-SSRS) Suicide Ideation Score

  Baseline, Follow-up (Week 8)

Study Arms (1)

Patients with MDD

EXPERIMENTAL

Participants will undergo 4 Transcranial Photobiomodulation (t-PBM) treatment visits and receive 1 irradiance dose per visit. The order of dose administration is randomized so patients receive each irradiance dose (50 mW/cm2; 300 mW/cm2; 770 mW/cm2), as well as a sham dose (0 mW/cm2), once over the 4 treatment visits.

Device: Transcranial Photobiomodulator; Device: Sham

Interventions

Transcranial Photobiomodulator DEVICE

Delivers laser-generated Near-Infrared Radiation (NIR) to forehead at 3 doses of irradiance - High (770 mW/cm2), Middle (300 mW/cm2), and Low (50 mW/cm2).

Also known as: LightForce® EXPi Deep Tissue Laser TherapyTM System, Transcranial PhotoBioModulation-1000 (tPBM-2.0)

Patients with MDD

Sham DEVICE

Transcranial Photobiomodulator delivers sham irradiance dose of 0 mW/cm2.

Patients with MDD

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must be able to give written informed consent and follow study procedures
• Participants must have major depressive disorder; all the following conditions need to be met to ensure presence of significant depression symptoms:
• Meeting diagnostic criteria for Major Depressive Disorder (MDD) in the past two weeks, at the DSM-5 Mini-International Neuropsychiatric Interview (MINI)
• Inventory for Depressive Symptomatology Clinician-rated (IDS-C) total score ≥23 at screening
• Depression symptoms are the primary target of treatment or treatment-seeking.
• Women of child-bearing potential must agree to use adequate contraception
• Participants taking medications or psychotherapy approved for the treatment of major depressive disorder will need to be stable for at least 8 weeks prior to screen

You may not qualify if:

• Unwilling or unable to comply with study requirements
• Participants who are judged to be at serious and imminent suicidal (C-SSRS≥4) or homicide risk, or currently in crisis such that inpatient hospitalization or other crisis management should take priority
• History of any or psychotic or bipolar disorder
• Alcohol or substance use disorder, post-traumatic stress disorder, obsessive-compulsive disorder and eating disorders within the preceding 12 months
• History of dementia, traumatic brain injury (TBI), or neurological disorders affecting the brain, including any history of stroke or seizure disorders requiring treatment in the last 5 years (even if controlled with medications)
• Cognitive impairment significant as determined by the Montreal Cognitive Assessment (MOCA) \<22
• History of antisocial personality disorder, or any clinically significant personality trait that would, in the investigator's judgment, preclude safe study participation or impair ability to remain adherent with the treatment protocol.
• History of significant treatment non-adherence or situations where the subjects are unlikely to adhere to treatment, in the opinion of the investigator
• Pregnant (as confirmed by pregnancy test at screen) or nursing.
• Currently undergoing device-based treatment for depression or taking medications for depression other than SSRIs or SNRIs.
• Treatment resistance with failure to respond to more than two adequate treatments with FDA-approved antidepressant medications during current episode of major depressive disorder.
• History of ECT in the last 12 months; lifetime history of VNS; lifetime treatment resistance to any FDA-approved device-based treatment for major depressive disorder; device-based interventions for depression will need to be discontinued at least 8 weeks prior to screen.
• Serious, unstable medical illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, hematologic disease; defined as any medical illness which is not well-controlled with standard-of-care medications
• Clinically significant abnormal findings of laboratory parameters including urine toxicology screen for drugs of abuse or at physical examination
• Clinical or laboratory evidence of uncontrolled hypothyroidism; if maintained on thyroid medication must be euthyroid for at least 1 month before screening.

Sponsors & Collaborators

• NYU Langone Health: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (3)

Massachusetts General Hospital

Charlestown, Massachusetts, 02129, United States

Location

New York University

New York, New York, 10016, United States

Location

Nathan Kline Institute

Orangeburg, New York, 10962, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Results Point of Contact

• Title: Dan Iosifescu, MD
• Organization: NYU Langone Health

Dan.Iosifescu@nyulangone.org

646-754-5156

Study Officials

• Dan Iosifescu, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2020
• First Posted: April 28, 2020
• Study Start: August 1, 2020
• Primary Completion: April 30, 2022
• Study Completion: June 24, 2022
• Last Updated: June 5, 2023
• Results First Posted: June 5, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• Access Criteria: The investigator who proposed to use the data and upon reasonable request. Requests should be directed to Dr. Kate Collins, PhD (email: Kate.Collins@nki.rfmh.org). To gain access, data requestors will need to sign a data access agreement.

Locations

US (3)