Transcranial Photobiomodulation for Alzheimer's Disease (TRAP-AD)

NCT04784416 | Active Not Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: 20-00865
• Study Type: interventional
• Target: 196
• Locations: 1 country
• Sites: 3

Brief Summary

This multi-site study will be the first to evaluate the dose-dependent effects of t-PBM in amnestic Mild Cognitive Impairment (aMCI) and early Alzheimer's Disease (AD) (CDR of 0.5-1, FAST 1-4; age 65-85) in a randomized clinical trial of 8 weeks of t-PBM vs. sham. At baseline, all subjects will complete initial neuropsychological testing. To elucidate mechanisms of action of t-PBM, prior to treatment, subjects will undergo neuroimaging related to critical features of AD: tau 18F MK-6240 load (PET), measures of brain bioenergetics (31P-MRS), and functional connectivity (rs-fMRI). After undergoing target engagement testing (t-PBM session performed during fMRI to detect BOLD changes with active t-PBM), subjects will then be randomized to t-PBM/sham and complete 24 t-PBM/sham treatments, \~11 min per day, 3 days per week, for 8 weeks. t-PBM will be administered via continuous, 808 nm wavelength laser delivery to the forehead bilaterally (at standard EEG electrode positions F4, F3).

Conditions

Alzheimer Disease; Mild Cognitive Impairment

Keywords

Transcranial Photobiomodulation

Outcome Measures

Primary Outcomes (1)

• Change in Repeatable Battery for the Assessment of Neuropsychological Status Update (RBANS) Total Scale Index Score.

  RBANS is s a brief, individually administered battery to measure cognitive decline or improvement. Total Scale Index Score Range = 40-160. A higher score indicates better performance.

  Baseline, Week 8

Secondary Outcomes (26)

• Change in Repeatable Battery for the Assessment of Neuropsychological Status Update (RBANS) Total Scale Index Score.

  Baseline, Month 3

• Addenbrooke's Cognitive Examination (ACE-III) Score

  Baseline

• Addenbrooke's Cognitive Examination (ACE-III) Score

  Week 8

• Addenbrooke's Cognitive Examination (ACE-III) Score

  Month 3

• Letter Comparison Test Score

  Baseline

Study Arms (2)

Transcranial Photobiomodulation (t-PBM)

EXPERIMENTAL

Device: Active tPBM-2.0; Drug: 18F-MK-6240

Sham

SHAM COMPARATOR

Device: Sham tPBM-2.0; Drug: 18F-MK-6240

Interventions

Active tPBM-2.0 DEVICE

The NIR continuous wave (average irradiance = 300 mW/cm2) will be used. The duration or irradiation will be for \~11 minutes (666 seconds).

Transcranial Photobiomodulation (t-PBM)

Sham tPBM-2.0 DEVICE

The sham mode (0 mW/cm2) will be used. The duration or sham "irradiation" will be for \~11 minutes (666 seconds).

Sham

18F-MK-6240 DRUG

PET tracer to be injected prior to PET imaging session, which will occur during baseline assessments

Sham; Transcranial Photobiomodulation (t-PBM)

Eligibility Criteria

• Age: 65 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Able to give written informed consent and follow study procedures.
• Age \> or = 65 years and \< or = 85 years.
• Meets the Petersen MCI criteria for Amnestic MCI (single and multiple domain) with a Clinical Dementia Rating (CDR) between 0.5-1.0, and a Functional Assessment Staging (FAST) of 1-4.
• Have at least a high school diploma/12 years of education.
• Participants with current mild MDD may be allowed to participate, given that mild MDD does not affect cognition and does not pose increased risk to the participant, as determined by site PI on a case-by-case basis.

You may not qualify if:

• Unwilling/unable to comply with study procedures.
• Other diagnosis of dementia (i.e. not Alzheimer's type), history of brain tumor, MRI evidence of brain damage or brain disease including significant trauma, hydrocephalus, seizures, intellectual disability, or other serious neurological disorder (e.g. Parkinson's disease or other movement disorders).
• History of significant cerebrovascular pathology (e.g., significant stroke). Subjects with a history of cardiovascular disease (e.g., myocardial infarction) will be allowed to participate at site PI's discretion, on a case-by-case basis, given that the cardiovascular disease is stable and does not reflect the presence of significant cerebrovascular pathology.
• Clinically unstable systemic medical disorders.
• Current DSM-5 diagnosis of alcohol or drug use disorder or other major psychiatric illness (e.g., schizophrenia, bipolar, PTSD, depression). Participants with current mild MDD may be allowed to participate, given that mild MDD does not affect cognition and does not pose increased risk to the participant, as determined by site PI on a case-by-case basis. Participants with current moderate/severe MDD will be excluded.
• Clinical or laboratory evidence of hypothyroidism.
• Clinically significant abnormal findings of laboratory parameters or at physical examination.
• Medications affecting cognition (e.g., narcotic analgesics; chronic use of medications with anticholinergic activity, anti-Parkinsonian medications, antipsychotic meds, etc.). Stable use (i.e., = 6 months) of memantine or acetylcholinesterase inhibitors will be allowed.
• Family history of early onset (\<60 y/o) dementia.
• Past intolerance or hypersensitivity to t-PBM.
• Significant skin conditions on the subject's scalp in the area of the procedure sites.
• Any use of light-activated drugs (photodynamic therapy) within 14 days prior to study enrollment.
• Any type of implants in the head, whose functioning might be affected by t-PBM.
• The completion of study imaging procedures is highly encouraged, but not mandatory for participants with extenuating circumstances (e.g., having prosthetic devices or metallic foreign bodies that constitute hazards for MRI, unable to get PET due to previous level of radiation exposure, having claustrophobia, having a large body size and shape).

Sponsors & Collaborators

• Alzheimer's Association: collaborator
• LiteCure LLC: collaborator
• NYU Langone Health: lead
• National Institutes of Health (NIH): collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Nathan Kline Institute

Orangeburg, New York, 10962, United States

Location

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Study Officials

• Dan Iosifescu, MD

  NYU Langone Health and Nathan Kline Institute

  PRINCIPAL INVESTIGATOR

• Ricardo Osorio, MD

  NYU Langone Health and Nathan Kline Institute

  PRINCIPAL INVESTIGATOR

• Paolo Cassano, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2021
• First Posted: March 5, 2021
• Study Start: April 27, 2021
• Primary Completion: October 30, 2025
• Study Completion: January 31, 2026
• Last Updated: December 9, 2025

Record last verified: 2025-12

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 will have access upon reasonable request.

Locations

US (3)