This is a proof-of-concept study designed to confirm that human phagocytic cells can be labeled with the near-infrared dye indocyanine green (ICG) and the presence of the labeled cells 48 hours later in cerebral cortex can be inferred using near infrared spectroscopy (NIRS).
To develop a method to detect dendritic cell recruitment in Alzheimer's disease (DC RAD), this study is designed in 2 parts. The first part assesses the safety and efficacy of indocyanine green (ICG) in labeling peripheral immune phagocytic cells in healthy adult subjects. The second part is designed to determine the presence of ICG in the brain of adult subjects diagnosed with Alzheimer's disease (AD). In the first part of the study, ICG will be delivered by intravenous infusion to healthy subjects to verify that peripheral immune phagocytic cells, of which DCs are a subset, can be labeled with ICG. If ICG labeling of phagocytic cells is confirmed, then in the second part of the study the presence of ICG in brain of AD patients, putatively carried in by ICG-labeled cells, will be investigated by NIRS using the INVOS 7000 cerebral oximeter.
Study Type
OBSERVATIONAL
Enrollment
46
CNS, A Division of APEX Innovative Sciences
Long Beach, California, United States
Treatment Emergent Adverse Events (TEAEs)
TEAE evaluations were reported on all randomized subjects who started infusion of ICG (Day 0) through 1 Week post infusion Telephone follow-up (Day 16) All AEs were followed until resolution. The number of participants may have experienced 1 or more TEAEs per Cohort. Participant numbers include Severity, TEAEs leading to Discontinuations, TEAEs leading to Intervention Discontinuation and severity and TEAEs leading to Death.
Time frame: Dosing (Day 0) through Telephone Follow-up (Day 16)
Electrocardiogram Results
The numbers of participants with overall ECG interpretations by the Investigator as Normal; Abnormal, Not Clinically significant (Abnormal NCS); and Abnormal, Clinically Significant (Abnormal CS) are completed at Screening, On Day 0, 30 minutes post start of ICG infusion and Day 2, 48 hours post start of infusion.
Time frame: Screening, Day 0 and Day 2
Mean ICG Concentrations
Mean concentrations of ICG with full ranges.
Time frame: Post Dosing time points: at 60 mins, 120 mins, 150 mins, 240 mins and 48 hours
Mean ICG Concentrations With Full Ranges (Post Hoc Analysis)
Cohorts 2A (3 subject and 3A (3 subjects) had no PK specimens drawn or analyzed at 48 hours that was specified in the a protocol a priori. Mean concentrations of ICG, measured with full ranges reported for cohorts 1 and 4. Cohorts 2 and 2A were combined and reported as a post-hoc analysis. Cohorts 3 and 3A were combined and reported as a post-hoc analysis.
Time frame: Post Dosing time points: at 60 mins, 120 mins, 150 mins, 240 mins and 48 hour
Change in Percentage (%) Labeling of Peripheral Blood Mononuclear Cells (PBMCs) Labeled With ICG
Change in percentage (%) labeling of PBMCs labeled with ICG, reported as a single measure (mean and standard deviation) for the cohorts between Day 0 (prior to infusion) and Day 2 (48 hours after the start of infusion).
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Time frame: Change between Day 0 (prior to infusion) and Day 2 (48 hours from the start of the initial dosing)
Change in Percentage (%) Labeling of Peripheral Blood Mononuclear Cells (PBMCs) Labeled With ICG (Post Hoc Analysis)
Change in percentage (%) labeling of PBMCs labeled with ICG (Mean and Standard Deviation) reported as a single measure for the specified cohorts between Day 0 (prior to infusion) and Day 2 (48 hours after the start of infusion). Cohorts 2 and 2A results were combined in this post hoc analysis and Cohorts 3 and 3A results were combined in this post hoc analysis.
Time frame: Change between Day 0 (prior to infusion) and Day 2 (48 hours from the start of the initial dosing)
Near-infrared Spectroscopy (NIRS) Measures
The amount of ICG in brain tissue was measured by near-infrared spectroscopy (NIRS). ICG absorbs near-infrared light in the same wavelength range as hemoglobin. This enabled the use of the INVOS 7100 Regional Oximeter, which measures the amount of near-infrared light (NIR-L) absorbed by hemoglobin in brain tissue, to be used to measure ICG levels in brain tissue at times after the start of infusion, expressed as percentage change in near-infrared (NIR-L) absorbance over the baseline level of absorbance due to hemoglobin prior to the start of the ICG infusion.
Time frame: Percentage change in NIR-L absorbance was measured at 60 mins. 120 mins, 150 mins, 240 mins and 48 hours after the start of the ICG infusion.
Near-infrared Spectroscopy (NIRS) Measures (Post-hoc Analysis)
The amount of ICG in brain tissue was measured by near-infrared spectroscopy (NIRS). ICG absorbs near-infrared light in the same wavelength range as hemoglobin. This enabled the use of the INVOS 7100 Regional Oximeter, which measures the amount of near-infrared light absorbed (NIR-L) by hemoglobin in brain tissue, to be used to measure ICG levels in brain tissue. ICG in brain tissue at times after the start of infusion, expressed as percentage change in near-infrared light (NIR-L) absorbance over the baseline level of absorbance due to hemoglobin prior to the start of ICG infusion.
Time frame: Percentage change in NIR-L absorbance was measured at 60 mins, 120 mins, 150 mins, 240 mins and 48 hours after the start of infusion