Clinical trial NCT04784416: Transcranial Photobiomodulation for Alzheimer's Disease (TRAP-AD)
Official title: Transcranial Photobiomodulation for Alzheimer's Disease (TRAP-AD)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Mild Cognitive Impairment
Alzheimer Disease
Keywords: Transcranial Photobiomodulation
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: Alzheimer's Association
name: LiteCure LLC
First posted: 2021-03-05
Enrollment: 125
Sex: ALL
Minimum age (years): 65
Maximum age (years): 85
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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).

Primary outcomes:
measure: Change in Repeatable Battery for the Assessment of Neuropsychological Status Update (RBANS) Total Scale Index Score.
timeFrame: Baseline, Week 8
Secondary outcomes:
measure: Change in Repeatable Battery for the Assessment of Neuropsychological Status Update (RBANS) Total Scale Index Score.
timeFrame: Baseline, Month 3
measure: Addenbrooke's Cognitive Examination (ACE-III) Score
timeFrame: Baseline
measure: Addenbrooke's Cognitive Examination (ACE-III) Score
timeFrame: Week 8
measure: Addenbrooke's Cognitive Examination (ACE-III) Score
timeFrame: Month 3
measure: Letter Comparison Test Score
timeFrame: Baseline
measure: Letter Comparison Test Score
timeFrame: Week 8
measure: Letter Comparison Test Score
timeFrame: Month 3
measure: Pattern Comparison Test Score
timeFrame: Baseline
measure: Pattern Comparison Test Score
timeFrame: Week 8
measure: Pattern Comparison Test Score
timeFrame: Month 3
measure: Stroop Color and Word Test (SCWT)
timeFrame: Baseline
measure: Stroop Color and Word Test (SCWT)
timeFrame: Week 8
measure: Stroop Color and Word Test (SCWT)
timeFrame: Month 3
measure: Difference in Score Between Trail Making Test-A (TMT-A) and Trail Making Test-B (TMT-B)
timeFrame: Baseline
measure: Difference in Score Between Trail Making Test-A (TMT-A) and Trail Making Test-B (TMT-B)
timeFrame: Week 8
measure: Difference in Score Between Trail Making Test-A (TMT-A) and Trail Making Test-B (TMT-B)
timeFrame: Month 3
measure: TMT-B T-Score
timeFrame: Baseline
measure: TMT-B T-Score
timeFrame: Week 8
measure: TMT-B T-Score
timeFrame: Month 3
measure: Face-Name Associative Memory Exam (FNAME-12) Score
timeFrame: Baseline
measure: Face-Name Associative Memory Exam (FNAME-12) Score
timeFrame: Week 8
measure: Face-Name Associative Memory Exam (FNAME-12) Score
timeFrame: Month 3
measure: Letter Number Sequencing Score
timeFrame: Baseline
measure: Letter Number Sequencing Score
timeFrame: Week 8
measure: Letter Number Sequencing Score
timeFrame: Month 3
measure: Change in Systemic Assessment for Treatment Emergent Events - Specific Inquiry (SAFTEE-SI) Score
timeFrame: Baseline, up to Week 8
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Orangeburg
country: United States
facility: Nathan Kline Institute
state: New York
Study officials:
affiliation: NYU Langone Health and Nathan Kline Institute
name: Dan Iosifescu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: NYU Langone Health and Nathan Kline Institute
name: Ricardo Osorio, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: Paolo Cassano, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: