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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04784416
Recruitment Status : Recruiting
First Posted : March 5, 2021
Last Update Posted : June 30, 2022
Sponsor:
Collaborators:
Alzheimer's Association
National Institutes of Health (NIH)
LiteCure LLC
Information provided by (Responsible Party):
NYU Langone Health

Brief Summary:
This study will be the first to evaluate the dose-dependent effects of t-PBM in amnestic Mild Cognitive Impairment (aMCI) (CDR of 0.5-1, FAST 1-3; age 65-85) in a randomized clinical trial of 8 weeks of t-PBM vs. sham. At screening, 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). Subjects will also undergo an open label t-PBM session performed during fMRI to detect BOLD changes with t-PBM. Subjects will then be randomized to t-PBM/sham and complete treatments in two participating centers (NYU/NKI acting as a single center, and MGH), ~10 min per day, 3 days per week, for 8 weeks. t-PBM will be administered via pulsed, 808nm wavelength laser delivery to the forehead bilaterally (at standard EEG electrode positions F4, F3).

Condition or disease Intervention/treatment Phase
Mild Cognitive Impairment Alzheimer Disease Device: Active tPBM-2.0 Device: Sham tPBM-2.0 Drug: 18F-MK-6240 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 125 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Transcranial Photobiomodulation for Alzheimer's Disease (TRAP-AD)
Actual Study Start Date : April 27, 2021
Estimated Primary Completion Date : June 30, 2025
Estimated Study Completion Date : November 30, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Transcranial Photobiomodulation (t-PBM) Device: Active tPBM-2.0
The NIR pulsed wave (irradiance =300 mW/cm2) will be used. The duration or irradiation will be for ~11 minutes (666 seconds).

Drug: 18F-MK-6240
PET tracer to be injected prior to PET imaging session, which will occur during baseline assessments

Sham Comparator: Sham 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).

Drug: 18F-MK-6240
PET tracer to be injected prior to PET imaging session, which will occur during baseline assessments




Primary Outcome Measures :
  1. Change in Repeatable Battery for the Assessment of Neuropsychological Status Update (RBANS) Total Scale Index Score. [ Time Frame: Baseline, Week 8 ]
    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.


Secondary Outcome Measures :
  1. Change in Repeatable Battery for the Assessment of Neuropsychological Status Update (RBANS) Total Scale Index Score. [ Time Frame: Baseline, Month 3 ]
    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.

  2. Addenbrooke's Cognitive Examination (ACE-III) Score [ Time Frame: Baseline ]
    ACE-III is a screening test that is composed of tests of attention, orientation, memory, language, visual perceptual and visuospatial skills. The total range of raw score is 0-100. A higher score indicates more intact cognitive functioning.

  3. Addenbrooke's Cognitive Examination (ACE-III) Score [ Time Frame: Week 8 ]
    ACE-III is a screening test that is composed of tests of attention, orientation, memory, language, visual perceptual and visuospatial skills. The total range of raw score is 0-100. A higher score indicates more intact cognitive functioning.

  4. Addenbrooke's Cognitive Examination (ACE-III) Score [ Time Frame: Month 3 ]
    ACE-III is a screening test that is composed of tests of attention, orientation, memory, language, visual perceptual and visuospatial skills. The total range of raw score is 0-100. A higher score indicates more intact cognitive functioning.

  5. Letter Comparison Test Score [ Time Frame: Baseline ]
    The total range of score is 0-21. A higher raw score indicates better performance.

  6. Letter Comparison Test Score [ Time Frame: Week 8 ]
    The total range of score is 0-21. A higher raw score indicates better performance.

  7. Letter Comparison Test Score [ Time Frame: Month 3 ]
    The total range of score is 0-21. A higher raw score indicates better performance.

  8. Pattern Comparison Test Score [ Time Frame: Baseline ]
    The total range of score is 0-30. A higher raw score indicates better performance.

  9. Pattern Comparison Test Score [ Time Frame: Week 8 ]
    The total range of score is 0-30. A higher raw score indicates better performance.

  10. Pattern Comparison Test Score [ Time Frame: Month 3 ]
    The total range of score is 0-30. A higher raw score indicates better performance.

  11. Stroop Color and Word Test (SCWT) [ Time Frame: Baseline ]
    SCWT is a neuropsychological test extensively used to assess the ability to inhibit cognitive interference that occurs when the processing of a specific stimulus feature impedes the simultaneous processing of a second stimulus attribute, well-known as the Stroop Effect. This study will use T-scores, range = 20 - 80. A higher T-score indicates better performance.

  12. Stroop Color and Word Test (SCWT) [ Time Frame: Week 8 ]
    SCWT is a neuropsychological test extensively used to assess the ability to inhibit cognitive interference that occurs when the processing of a specific stimulus feature impedes the simultaneous processing of a second stimulus attribute, well-known as the Stroop Effect. This study will use T-scores, range = 20 - 80. A higher T-score indicates better performance.

  13. Stroop Color and Word Test (SCWT) [ Time Frame: Month 3 ]
    SCWT is a neuropsychological test extensively used to assess the ability to inhibit cognitive interference that occurs when the processing of a specific stimulus feature impedes the simultaneous processing of a second stimulus attribute, well-known as the Stroop Effect. This study will use T-scores, range = 20 - 80. A higher T-score indicates better performance.

  14. Difference in Score Between Trail Making Test-A (TMT-A) and Trail Making Test-B (TMT-B) [ Time Frame: Baseline ]

    Trails Making Test (Trails) is a neuropsychological test of visual attention and task switching. Both parts of the Trail Making Test consist of 25 circles distributed over a sheet of paper. In Part A, the circles are numbered 1-25, and the patient should draw lines to connect the numbers in ascending order. In Part B, the circles include both numbers (1-13) and letters (A-L); as in Part A, the patient draws lines to connect the circles in an ascending pattern (alternating numbers and letters). The time it takes to connect the "trail" is recorded.

    Reported as B - A. Range = 0 - 100+ (measured in seconds). A higher B - A score indicates poorer performance.


  15. Difference in Score Between Trail Making Test-A (TMT-A) and Trail Making Test-B (TMT-B) [ Time Frame: Week 8 ]

    Trails Making Test (Trails) is a neuropsychological test of visual attention and task switching. Both parts of the Trail Making Test consist of 25 circles distributed over a sheet of paper. In Part A, the circles are numbered 1-25, and the patient should draw lines to connect the numbers in ascending order. In Part B, the circles include both numbers (1-13) and letters (A-L); as in Part A, the patient draws lines to connect the circles in an ascending pattern (alternating numbers and letters). The time it takes to connect the "trail" is recorded.

    Reported as B - A. Range = 0 - 100+ (measured in seconds). A higher B - A score indicates poorer performance.


  16. Difference in Score Between Trail Making Test-A (TMT-A) and Trail Making Test-B (TMT-B) [ Time Frame: Month 3 ]

    TMT is a neuropsychological test of visual attention and task switching. Both parts of the Trail Making Test consist of 25 circles distributed over a sheet of paper. In Part A, the circles are numbered 1-25, and the patient should draw lines to connect the numbers in ascending order. In Part B, the circles include both numbers (1-13) and letters (A-L); as in Part A, the patient draws lines to connect the circles in an ascending pattern (alternating numbers and letters). The time it takes to connect the "trail" is recorded.

    Reported as B - A. Range = 0 - 100+ (measured in seconds). A higher B - A score indicates poorer performance.


  17. TMT-B T-Score [ Time Frame: Baseline ]
    In TMT-B, the circles include both numbers (1-13) and letters (A-L); the patient draws lines to connect the circles in an ascending pattern (alternating numbers and letters). The time is takes to connect the "trail" is recorded. Range = 0 - 100. A higher T-score indicates better performance

  18. TMT-B T-Score [ Time Frame: Week 8 ]
    In TMT-B, the circles include both numbers (1-13) and letters (A-L); the patient draws lines to connect the circles in an ascending pattern (alternating numbers and letters). The time is takes to connect the "trail" is recorded. Range = 0 - 100. A higher T-score indicates better performance

  19. TMT-B T-Score [ Time Frame: Month 3 ]
    In TMT-B, the circles include both numbers (1-13) and letters (A-L); the patient draws lines to connect the circles in an ascending pattern (alternating numbers and letters). The time is takes to connect the "trail" is recorded. Range = 0 - 100. A higher T-score indicates better performance

  20. Face-Name Associative Memory Exam (FNAME-12) Score [ Time Frame: Baseline ]
    FNAME-12 is an associative memory test where participants see a series of facial photos and names and are asked to remember the face-name pairs.

  21. Face-Name Associative Memory Exam (FNAME-12) Score [ Time Frame: Week 8 ]
    FNAME-12 is an associative memory test where participants see a series of facial photos and names and are asked to remember the face-name pairs.

  22. Face-Name Associative Memory Exam (FNAME-12) Score [ Time Frame: Month 3 ]
    FNAME-12 is an associative memory test where participants see a series of facial photos and names and are asked to remember the face-name pairs.

  23. Letter Number Sequencing Score [ Time Frame: Baseline ]
    this study will use T-scores, range = 20 - 80. A higher T-score indicates better performance.

  24. Letter Number Sequencing Score [ Time Frame: Week 8 ]
    this study will use T-scores, range = 20 - 80. A higher T-score indicates better performance.

  25. Letter Number Sequencing Score [ Time Frame: Month 3 ]
    this study will use T-scores, range = 20 - 80. A higher T-score indicates better performance.

  26. Change in Systemic Assessment for Treatment Emergent Events - Specific Inquiry (SAFTEE-SI) Score [ Time Frame: Baseline, up to Week 8 ]
    SAFTEE-SI is a list of 55 symptoms. Participants indicate how bothersome each symptom has been for them by circling the appropriate number (0-none, 1-mild, 2-moderate, 3-severe). The total range of score is 0 - 165. The higher the score, the more severely bothersome the symptoms are.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   65 Years to 85 Years   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Able to give written informed consent and follow study procedures.
  2. Age ≥ 65 years and ≤ 85 years.
  3. Meets the Petersen MCI criteria for Amnestic MCI (single and multiple domain) with a Clinical Dementia Rating (CDR) between 0.5 to 1, and a Functional Assessment Staging (FAST) of 1-3.
  4. Consents to permit and identifies a willing informed relative, family member, or spouse for study staff to interview to confirm subject reports as per UDS 3.0 guidelines.
  5. Have at least a high school diploma / 12 years education

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 cardiovascular or cerebrovascular pathology (e.g., myocardial infarction; stroke).
  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).
  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. Body size and shape not allowing for a comfortable fit in PET and MRI scanners.
  11. Past intolerance or hypersensitivity to t-PBM.
  12. Significant skin conditions on the subject's scalp in the area of the procedure sites.
  13. Any use of light-activated drugs (photodynamic therapy) within 14 days prior to study enrollment.
  14. Any type of implants in the head, whose functioning might be affected by t-PBM, or any prosthetic devices (e.g., pacemaker or surgical clips) that constitutes a hazard for MRI imaging.
  15. Claustrophobia or metallic foreign bodies that would preclude MRI.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04784416


Contacts
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Contact: Dan Iosifescu, MD 646-754-5156 dan.iosifescu@nyulangone.org
Contact: Xiaotong Song 646-754-2211 xiaotong.song@nyulangone.org

Locations
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United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Paolo Cassano, MD, PhD    617-726-6421    PCASSANO@mgh.harvard.edu   
Contact: MGH Team    617-724-8780    pbm@mgh.harvard.edu   
Principal Investigator: Paolo Cassano, MD, PhD         
Sub-Investigator: Aura Hurtado, MD         
Sub-Investigator: Eva Ratai, PhD         
United States, New York
NYU Langone Health Recruiting
New York, New York, United States, 10016
Contact: Dan Iosifescu, MD    646-754-5156    dan.iosifescu@nyulangone.org   
Contact: Zanetta Kovbasyuk    212-263-7563    zanetta.kovbasyuk@nyulangone.org   
Principal Investigator: Dan Iosifescu, MD         
Principal Investigator: Ricardo Osorio, MD         
Sub-Investigator: Martin Sadowski, MD, PhD, DSci         
Sub-Investigator: Ryan Brown, PhD         
Sub-Investigator: Eva Petkova, PhD         
Sub-Investigator: Thaddeus Tarpey, PhD         
Nathan Kline Institute Recruiting
Orangeburg, New York, United States, 10962
Contact: Dan Iosifescu, MD    646-754-5156    dan.iosifescu@nyulangone.org   
Contact: Molly Irvin    845-398-7752    molly.irvin@nki.rfmh.org   
Principal Investigator: Dan Iosifescu, MD         
Principal Investigator: Ricardo Osorio, MD         
Sub-Investigator: Antonio Convit, MD         
Sub-Investigator: Kathy Yates, PhD         
Sub-Investigator: Nunzio Pomara, MD         
Sub-Investigator: Matthew Hoptman, PhD         
Sub-Investigator: Umit Tural, MD         
Sub-Investigator: Katherine Collins, MSW, PhD         
Sponsors and Collaborators
NYU Langone Health
Alzheimer's Association
National Institutes of Health (NIH)
LiteCure LLC
Investigators
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Principal Investigator: 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
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Responsible Party: NYU Langone Health
ClinicalTrials.gov Identifier: NCT04784416    
Other Study ID Numbers: 20-00865
First Posted: March 5, 2021    Key Record Dates
Last Update Posted: June 30, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) will be provided upon reasonable request.
Supporting Materials: Study Protocol
Statistical Analysis Plan (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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by NYU Langone Health:
Transcranial Photobiomodulation
Additional relevant MeSH terms:
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Alzheimer Disease
Cognitive Dysfunction
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cognition Disorders