Alzheimer's disease dementia
Conditions
Interventions
None listed
Sponsors
Centre for Human Drug Research
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Inclusion criteria for AD Patients , Healthy volunteers for brain and whole body imaging 1. Participants must be able to understand the information provided on purpose and conduct of the clinical study, must be capable of giving fully informed consent in writing, and have read and signed the informed consent prior to study participation. 2. Male or females >= 50 years of age. 3. Females of child-bearing potential must provide: - Agreement to practice adequate contraception methods (abstinence, intrauterine contraceptive device [IUCD], condoms, oral contraceptives, or other adequate barrier contraception) - barrier contraception has to be in combination with local application of a spermicide and - Negative urine pregnancy test results (beta-HCG) For females >= 60 years of age postmenopausal status will be determined by medical history (last spontaneous bleeding at least 1 year prior to radiotracer administration or hysterectomy or a bilateral oophorectomy at least three months prior to radiotracer administration).;Additional inclusion criteria for healthy volunteers for brain imaging only 1. Adequate visual and auditory acuity to complete neuropsychological testing. 2. MMSE score of >= 28 3. CDR score of zero (0) 4. Confirmation by other neuropsychological test results that the volunteer does not show any signs of cognitive impairment or dementia (e.g. results lying within an interval of one standard deviation from the mean value, mean value and standard deviations adjusted for age and education);Additional inclusion criteria for probable AD patients only 1. Adequate visual and auditory acuity to complete neuropsychological testing. 2. Patient fulfills DSM-IV and NINCDS-ADRDA criteria for probable AD, which are cognitive deficits such as memory decline and impairment in at least one other cognitive domain (aphasia, apraxia, agnosia or executive dysfunction). 3. Patient has mild to moderate dementia : - with a dementia score of >= 20 on the Mini-Mental Status Examination (MMSE) - with a Clinical Dementia Rating score of 1 or 2 (CDR) 4. Patient has had the following further tests: - Neurological examination - Psychometric testing - Brain MRI
Exclusion criteria
Exclusion criteria: Exclusion criteria: healthy volunteers for brain and whole body imaging and probable AD patients 1. Any disease, condition, or concomitant medications that significantly compromises the function of the body systems and could result in excessive accumulation, impaired metabolism, altered excretion of the radiotracer, or might interfere with the conduct of the study or interpretation of the results. 2. Current unstable medical condition (e.g. unstable angina, myocardial infarction or coronary revascularization in the preceding 12 months, cardiac failure, chronic renal failure, chronic hepatic disease, severe pulmonary disease, blood disorders, poorly controlled diabetes, chronic infection) 3. Current systemic autoimmune disease or clinically relevant systemic inflammatory disease. 4. History of cancer or current cancer, including brain tumors. 5. History of or current alcohol or drug abuse/dependence or suspicion of alcohol or drug abuse/dependence. 6. History of anaphylactoid or anaphylactic reactions to any allergen including drugs and contrast media. 7. Pregnancy or lactation. 8. History of significant occupational exposure to ionizing radiation or application of radioactive substances or ionizing radiation for the purposes of diagnosis or treatment within the last year according to recommendations from current guidelines, or whose occupational exposure to radioactivity is monitored or (Netherlands only) application of radioactive substances or ionizing exposure to radiation during an investigation / study in the year preceding the PET scan 9. Haematological or biochemical parameters that are outside the normal range and are considered clinically significant by the investigator, in particular the presence of hepatitis B virus surface antigen (HBsAg), hepatitis C virus antibodies (anti-HCV) or human immune deficiency virus antibodies (anti-HIV). Minor deviations in lab parameters that are considered by the evaluating physician to be not clinically significant with respect to safety or interpretation of study results are not considered an exclusion criterion. 10. Clinically relevant findings in the 12 lead ECG as determined by evaluating physician. 11. Donation of blood within 4 weeks (12 weeks for Finland only) or plasmapheresis within 2 weeks before the radiotracer administration. 12. Criteria which in the opinion of the investigator preclude participation for scientific reasons, for reasons of compliance, or for reasons of the subject*s safety. 13. Subject is in custody by order of an authority or a court of law. 14. Exclusion periods from other studies or simultaneous participation in other clinical studies or previous assignment to radiotracer administration in this study. 15. Close affiliation with the investigational site (e.g. close relative of investigator), dependent person (e.g. employee or student of investigational site).;Additional exclusion criteria for healthy volunteers for brain imaging and probable AD patients only 1. Evidence for, history of or imaging findings indicative of any neurological disease (AD patients: other than Alzheimer*s disease, including other dementias) or psychiatric disorder, including e.g. brain surgery, intracranial hematoma, stroke/cerebrovascular disease, epilepsy, inflammatory or infectious disease, severe depression, attempted suicide or current suicidal ideation. 2. MRI brain scan findings that rev
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary variables are captured for probable AD patients and healthy volunteers undergoing PET brain imaging: - Standard quantification variables for each ROI/VOI derived from 3D PET imaging and brain modeling, in particular distribution volume (DV) and binding potential (BP), using different modeling approaches | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary variables are captured for probable AD patients and healthy volunteers undergoing PET brain imaging: - SUV values for each ROI/VOI at several time points when maximal separation between AD patients and healthy volunteers is indicated. - Visual analysis/description of uptake: The degree of uptake in different brain regions will be rated on a 3-point scale. - Classification of PET scans to cohorts (probable AD patients, healthy volunteers) by evaluation of a predefined scoring system based on visual analysis/description of brain PET scans. The following pharmacokinetic variables are only captured for probable AD patients and healthy volunteers undergoing PET brain imaging: - Arterial blood concentration of total 18F-radioactivity (comprising all 18F-labeled substances) and of non-metabolized [18F]DPA-714, and the pharmacokinetic parameters: Cmax (KBq/L and %ID/g); tmax (h); AUC(0-tlast) (KBq*h/L, %ID*h/L). - Arterial plasma-concentrations of non-metabolized DPA-714 (i.e. the sum of [18F]DPA-714 and [19F]DPA-714), in pmol/L and the pharmacokinetic parameters: (Cmax (pmol/L); Cmax/D (1/L); tmax (h); AUC(0-tlast) (pmol*h/L); AUC(0-tlast)/D (h/L); AUC (pmol*h/L); AUC/D (h/L); CL (L/h), Vss (L); Vz (L); t1/2 (h); MRT (h). Dosimetry data are only captured for healthy volunteers undergoing whole body imaging: - Whole body biodistribution in % injected dose over time and radiation dosimetry estimates (in mGy/MBq) and effective dose (ED) (in mSv/MBq) per tissue/organ of [18F]DPA-714 - Venous blood and plasma-concentrations of total 18F-radioactivity expressed in KBq/L and %ID/g. - Urine: Concentration of renally excreted total radioactivity (18F) during each collection period and during the whole observation period expressed in MBq/L and % of radioactive dose Safety variables include: - Adverse events - Physical examination - Vital signs (blood pressure, heart rate), and body temperature - 12-lead ECG - Laboratory evaluation of veno | — |
Countries
Netherlands
Outcome results
None listed