Alzheimer Disease
Conditions
Keywords
Inflammation, PET scans
Brief summary
This study is being done to learn about inflammation in the brain of those with Alzheimer's disease (AD). The purpose of this study is to determine if 11C-ER176 is able to accurately measure inflammation in patients with Alzheimer's disease. Both patients (with either mild cognitive impairment (MCI) or Alzheimer's disease) and healthy controls (participants without memory complaints or impairment) will be included in this study.
Detailed description
Inflammation likely plays a role in the damage to the brain caused by Alzheimer's disease. Accurately measuring inflammation in the brain could provide new information about the mechanisms that cause Alzheimer's disease, and could help identify new treatments that reduce inflammation. Positron emission tomography (PET) imaging is a type of brain scanning method that allows investigators to measure small molecules in the brain. ER176-PET was recently developed as an improved method for measuring brain inflammation. However, ER176-PET has not yet been used in patients with Alzheimer's disease. The investigators propose to use ER176-PET imaging in subjects with mild cognitive impairment (a very early stage of Alzheimer's disease) or mild Alzheimer's disease to compare the amount of inflammation with that seen in older control subjects. The investigators will first use a gold standard method of measuring ER176 in brain that requires sampling arterial blood during the scan. The investigators will compare these results to those obtained using novel methods that don't require blood sampling. The investigators hope to show that ER176 is a useful tool for measuring inflammation in Alzheimer's disease, and that the investigators can develop a way to obtain ER176 PET scans that don't require arterial blood sampling. This study uses a special type of scan called a PET scan to take pictures of the brain. During the PET scan, a special dye is injected into the body. Two types of dye will be used in this study: Florbetaben and 11C-ER176. Florbetaben sticks to amyloid plaques, which are in the brain in Alzheimer's disease. Florbetaben has been approved by the Food and Drug Administration to help diagnose Alzheimer's disease. 11C-ER176 sticks to parts of the brain where there is inflammation. Past studies have shown that inflammation is present in the brains of patients with Alzheimer's disease.
Interventions
DRUGFlorbetaben
Florbetaben sticks to amyloid plaques, which are in the brain in Alzheimer's disease.
DRUG11C-ER176
11C-ER176 sticks to parts of the brain where there is inflammation. Past studies have shown that inflammation is present in the brains of patients with Alzheimer's disease. The purpose of this study is to determine if 11C-ER176 is able to accurately measure inflammation in patients with Alzheimer's disease.
Sponsors
Columbia University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Age 50 and older 2. Meet criteria for either a) amnestic mild cognitive impairment or Alzheimer's disease, or b) have no cognitive impairment 3. If you are unable to provide informed consent, you must have a surrogate decision maker and be able to verbally assent to the study procedures 4. Written and oral fluency in English 5. Able to participate in all scheduled evaluations and to complete all required tests and procedures. 6. In the opinion of the investigator, you must be considered likely to comply with the study protocol and to have a high probability of completing the study.
Exclusion criteria
1. Past or present history of certain brain disorders other than MCI or AD. 2. Certain significant medical conditions, which make study procedures of the current study unsafe. Such serious medical conditions include uncontrolled epilepsy and multiple serious injuries. 3. Contraindication to MRI scanning 4. Conditions precluding entry into the scanners (e.g. morbid obesity, claustrophobia, etc.). 5. Exposure to research related radiation in the past year that, when combined with this study, would place you above the allowable limits. 6. Participation in the last year in a clinical trial for a disease modifying drug for AD. 7. Inability to have a catheter in your vein for the injection of radioligand. 8. Inability to have blood drawn from your veins. 9. Taking anticoagulant medication (e.g., warfarin).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 11C-ER176 Total Distribution Volume | Up to one year from baseline | Total distribution volume reflects the amount of TSPO (the inflammatory protein that 11C-ER176 sticks to) in the brain. This measure requires arterial blood sampling. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 11C-ER176 Standardized Uptake Value Ratio | Up to one year from baseline | The standardize uptake value ratio is the concentration of radioactivity measured from the 11C-ER176 positron emission tomography (PET) scan in the cortex compared to the uptake in the cerebellum (pseudo-reference region). This is a simplified quantification technique compared to the Total Distribution Volume, but is linearly related to it. Higher values indicate more neuroinflammation. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cognitive Impairment Alzheimer's disease (mild cognitive impairment or mild stage Alzheimer's disease dementia)
11C-ER176: 11C-ER176 sticks to parts of the brain where there is inflammation. Past studies have shown that inflammation is present in the brains of patients with Alzheimer's disease. The purpose of this study is to determine if 11C-ER176 is able to accurately measure inflammation in patients with Alzheimer's disease.
Florbetaben: Florbetaben sticks to amyloid plaques, which are in the brain in Alzheimer's disease. | 6 |
| No Cognitive Impairment Healthy Controls
11C-ER176: 11C-ER176 sticks to parts of the brain where there is inflammation. Past studies have shown that inflammation is present in the brains of patients with Alzheimer's disease. The purpose of this study is to determine if 11C-ER176 is able to accurately measure inflammation in patients with Alzheimer's disease.
Florbetaben: Florbetaben sticks to amyloid plaques, which are in the brain in Alzheimer's disease. | 1 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Screen fail | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Cognitive Impairment | No Cognitive Impairment | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 1 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 1 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 0 Participants | 6 Participants |
| Region of Enrollment United States | 6 participants | 1 participants | 7 participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 4 Participants | 1 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 1 |
| other Total, other adverse events | 0 / 6 | 0 / 1 |
| serious Total, serious adverse events | 0 / 6 | 0 / 1 |
Outcome results
Primary
11C-ER176 Total Distribution Volume
Total distribution volume reflects the amount of TSPO (the inflammatory protein that 11C-ER176 sticks to) in the brain. This measure requires arterial blood sampling.
Time frame: Up to one year from baseline
Population: Data is reflective of those with blood sampling only: 4 out of 6 cognitive impairment participants and 1 out of 1 no cognitive impairment participant. All 7 completers have 11C-ER176 imaging but only 5 have arterial blood sampling and therefore a Total Distribution Volume.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cognitive Impairment | 11C-ER176 Total Distribution Volume | 6.27 mL/cm^3 |
| No Cognitive Impairment | 11C-ER176 Total Distribution Volume | 9.32 mL/cm^3 |
Secondary
11C-ER176 Standardized Uptake Value Ratio
The standardize uptake value ratio is the concentration of radioactivity measured from the 11C-ER176 positron emission tomography (PET) scan in the cortex compared to the uptake in the cerebellum (pseudo-reference region). This is a simplified quantification technique compared to the Total Distribution Volume, but is linearly related to it. Higher values indicate more neuroinflammation.
Time frame: Up to one year from baseline
Population: Data is analyzed for completers only: 6 out of 6 cognitive impairment participants and 1 out of 1 no cognitive impairment participant. Completers here meaning they have 11C-ER176 imaging and SUVRs.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cognitive Impairment | 11C-ER176 Standardized Uptake Value Ratio | 1.19 uptake value ratio |
| No Cognitive Impairment | 11C-ER176 Standardized Uptake Value Ratio | 1.22 uptake value ratio |