Exploratory Open-Label Study For the Development of a Method To Detect Dendritic Cell Recruitment in Alzheimer's Disease (DC RAD)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- Treatment Emergent Adverse Events (TEAEs)
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 21 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All Healthy Subjects:
- •Subjects are determined by the investigator to be medically stable and expected to complete the trial as designed.
- •Subjects have adequate hearing, vision, and language skills to perform neuropsychiatric testing and interviews as specified in the protocol.
- •Subjects are able to understand and agree to comply with the study procedures and report for scheduled office visits.
- •Subjects are able to reliably communicate with study personnel about adverse events (AEs) and concomitant medications.
- •Signed written informed consent according to institutional guidelines.
- •Healthy Adult subjects: Male or female and between the ages of 21 to 55 inclusive.
- •Healthy Elderly subjects: Male or female and between the ages of 65 to 90 inclusive MMSE score between 15 and
- •Alzheimer's Subjects: Male or female and between the ages of 50 to 90 inclusive. Patients satisfying the criteria for the clinical diagnosis of probable AD based on National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) . OR 6 months documented cognitive decline by physician OR Amyloid or Tau pathology confirmed by PET scan with ligand. MMSE score between 16 and 25 and Modified Hachinski Ischemia Scale (MHIS) score of ≤ 4.
排除标准
- •Sex and Reproductive Status:
- •Women who test positive for pregnancy.
- •Pre-menopausal women who are not practicing two methods of birth control for 3 months prior and a week after the ICG infusion.
- •Medical History:
- •Subjects with a history of any anaphylactic reactions.
- •Subjects with a history of allergic reaction to ICG.
- •Subjects with a history of iodine sensitivity and/or allergic reaction to iodine.
- •Subjects with a history of a clinically significant hepatic disease.
- •Target Disease Exceptions:
- •Any subject diagnosed to have an autoimmune disorder including (Psoriasis, Lupus, Rheumatoid arthritis, Crohn's disease, multiple sclerosis, and alopecia areata).
- •Any subject who has any unstable cardiovascular (included uncontrolled hypertension), pulmonary, or GI disease.
- •For Alzheimer's patients, a medical condition other than AD that could explain or contribute significantly to the patient's dementia.
- •Concurrent Medications:
- •Any subject who is immunocompromised at screening including taking medications that are systemic immunosuppressives including corticosteroids but not NSAIDS.
- •Any subject currently prescribed a biologic immunosuppressive therapy or having taken such therapy in the prior 3 months.
- •Physical and Laboratory Test Findings at Screening:
- •Any subject with uncontrolled hypertension at screening.
- •Any subject with hepatic or hematological abnormalities at screening.
- •Any subject who has a known infection with a human immunodeficiency virus.
研究组 & 干预措施
Cohort 1
Cohort 1, healthy adults (n = 5), will receive an ICG infusion in NSS of 1 mg/min for 120 minutes.
Cohort 2
If no dose limiting adverse effects are observed in Cohort 1, then Cohort 2, healthy adults (n = 10), will receive an ICG infusion in NSS of 2 mg/min for 120 minutes. If there are no dose limiting adverse events and there is evidence of ICG-labeling of PBMCs, the 2 mg/min infusion rate will be used for the remainder of the study.
Cohort 2A
Cohort 2A, Three healthy adults, will receive an ICG in D5W (change in IV material) infusion of 2 mg/min for 120 minutes. If no adverse effects are observed with D5W infusion material then proceed to Cohort 3A healthy elderly
Cohort 3
Cohort 3, healthy elderly adults, will receive an ICG infusion in NSS of 2 mg/min for 120 minutes. The first 5 subjects will serve as a satellite group. If no adverse effects are observed in the satellite group, then a further 10 healthy elderly adults will receive a 2 mg/min ICG infusion (n = 15 total for Cohort 3).
Cohort 3A,
Cohort 3A, Three healthy elderly adults, will receive an ICG in D5W (change in IV material) infusion of 2 mg/min for 120 minutes. If no adverse effects are observed with D5W infusion material then proceed to Cohort 4 of probable AD subjects
Cohort4,
Cohort 4, Probable AD patients, will receive an ICG infusion of D5W of 2 mg/min for 120 minutes. The first 5 subjects will serve as a satellite group. If no adverse effects are observed, then a further 10 AD patients will receive a 2 mg/min ICG infusion (n = 15 total for Cohort 4). Recruitment of AD patients will begin if there are no dose limiting adverse effects observed in the satellite group of healthy elderly.
结局指标
主要结局
Treatment Emergent Adverse Events (TEAEs)
时间窗: Dosing (Day 0) through Telephone Follow-up (Day 16)
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.
Electrocardiogram Results
时间窗: Screening, Day 0 and Day 2
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.
Mean ICG Concentrations
时间窗: Post Dosing time points: at 60 mins, 120 mins, 150 mins, 240 mins and 48 hours
Mean concentrations of ICG with full ranges.
Mean ICG Concentrations With Full Ranges (Post Hoc Analysis)
时间窗: Post Dosing time points: at 60 mins, 120 mins, 150 mins, 240 mins and 48 hour
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.
Change in Percentage (%) Labeling of Peripheral Blood Mononuclear Cells (PBMCs) Labeled With ICG
时间窗: Change between Day 0 (prior to infusion) and Day 2 (48 hours from the start of the initial dosing)
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).
Change in Percentage (%) Labeling of Peripheral Blood Mononuclear Cells (PBMCs) Labeled With ICG (Post Hoc Analysis)
时间窗: Change between Day 0 (prior to infusion) and Day 2 (48 hours from the start of the initial dosing)
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.
Near-infrared Spectroscopy (NIRS) Measures
时间窗: 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.
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.
Near-infrared Spectroscopy (NIRS) Measures (Post-hoc Analysis)
时间窗: 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
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.
次要结局
未报告次要终点