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

NCT ID: NCT04784416

Last Updated: 2025-12-09

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 196 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-27
• Study Completion Date: 2026-01-31

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

Mild Cognitive Impairment; Alzheimer Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Transcranial Photobiomodulation (t-PBM)

Group Type: EXPERIMENTAL

Active tPBM-2.0

Intervention Type: DEVICE

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

18F-MK-6240

Intervention Type: DRUG

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

Sham

Group Type: SHAM_COMPARATOR

Sham tPBM-2.0

Intervention Type: DEVICE

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

18F-MK-6240

Intervention Type: DRUG

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

Interventions

Active tPBM-2.0

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

Intervention Type: DEVICE

Sham tPBM-2.0

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

Intervention Type: DEVICE

18F-MK-6240

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Able to give written informed consent and follow study procedures.

2. Age > or = 65 years and < or = 85 years.

3. 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.

4. Be willing to identify an informed relative, family member, spouse, or friend for study staff to interview to confirm subject reports as per UDS 3.0 guidelines; however the lack of a study informant is not exclusionary.

5. Have at least a high school diploma/12 years of education.

6. 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.

Exclusion Criteria

1. Unwilling/unable to comply with study procedures.

2. 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).

3. 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.

4. Clinically unstable systemic medical disorders.

5. 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.

6. Clinical or laboratory evidence of hypothyroidism.

7. Clinically significant abnormal findings of laboratory parameters or at physical examination.

8. 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.

9. Family history of early onset (<60 y/o) dementia.

10. Past intolerance or hypersensitivity to t-PBM.

11. Significant skin conditions on the subject's scalp in the area of the procedure sites.

12. Any use of light-activated drugs (photodynamic therapy) within 14 days prior to study enrollment.

13. Any type of implants in the head, whose functioning might be affected by t-PBM.

14. 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).

• Minimum Eligible Age: 65 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Alzheimer's Association

OTHER

Sponsor Role: collaborator

LiteCure LLC

INDUSTRY

Sponsor Role: collaborator

NYU Langone Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dan Iosifescu, MD

Role: PRINCIPAL_INVESTIGATOR

NYU Langone Health and Nathan Kline Institute

Ricardo Osorio, MD

Role: PRINCIPAL_INVESTIGATOR

NYU Langone Health and Nathan Kline Institute

Paolo Cassano, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

NYU Langone Health

New York, New York, United States

Nathan Kline Institute

Orangeburg, New York, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

20-00865

Identifier Type: -

Identifier Source: org_study_id