Alzheimer's disease and healthy controls (2 groups: 1 group with young healthy volunteers, 1 group with elderly healthy volunteers) MedDRA version: 16.1 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852
Conditions
Interventions
Product Name: Tariquidar
Product Code: XR9576
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: TARIQUIDAR
CAS Number: 206873-63-4
Current Sponsor code: XR9576
Other descriptive name: TA
Sponsors
Medizinische Universität Wien, Universitätsklinik für Klinische Pharmakologie
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • signed informed consent • age: =18 years old • physical examination and laboratory analysis: no presence of clinically relevant abnormal findings or values which the investigator considers may interfere with the objectives of the present study • no diseases, which the investigator considers may affect the outcome of the study • ability to comprehend the full nature and purpose of the study, including possible risks and side effects Patient group (additionally): • Diagnosis of probable Alzheimer’s disease based on the NINCDS/ADRDA criteria . The severity of AD in a range from mild to moderate, which is in accordance with a MMSE score =12 and =26. The Hachinski score must be =65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: • Unwillingness to sign the informed consent • age:4, MMSE score out of the range of =12 and =26 • patients and/or caregiver with probable compliance problems
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this study is to examine differences in Pgp function at the BBB between AD patients and age-matched control subjects by performing (R)-11C-verapamil PET scans before, during and after Pgp modulation with tariquidar. Tariquidar will be administered at a dose of 3 mg/kg which corresponds to the half-maximum effect dose for inhibition of Pgp at the BBB. We hypothesize that AD patients will show higher increases in (R)-11C-verapamil brain distribution following tariquidar administration than control subjects due to reduced cerebral Pgp function in AD patients. Furthermore the influence of ABCB1 single nucleotide polymorphisms (SNPs, 3435C>T, 2677G>T, 1236C>T) on (R)-11C-verapamil distribution to the brain before, during and after tariquidar infusion will be assessed. ? To compare rate constants of (R)-11C-verapamil transport across the BBB before, during and after tariquidar infusion between AD patients and age-matched control subjects. Secondary objectives: ;Secondary Objective: ? To assess the influence of ABCB1 SNPs on (R)-11C-verapamil brain distribution before, during and after tariquidar infusion in AD patients and age-matched control subjects. ? To assess regional differences in (R)-11C-verapamil brain distribution before, during and after tariquidar infusion in AD patients and age-matched control subjects. ? To compare tariquidar plasma pharmacokinetics in AD patients and age-matched control subjects. ? To assess age dependency of cerebral Pgp function before and after pharmacological modulation.;Primary end point(s): Transfer rate constants of 11C-verapamil before and after tariquidar infusion as calculated by pharmacokonetic modeling;Timepoint(s) of evaluation of this end point: end of study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Modeling the slope of 11C-verapamil brain uptake increase as response to tariquidar infusion; Genetic analysis;Timepoint(s) of evaluation of this end point: End of study | — |
Countries
Austria
Contacts
Public ContactKlinische Pharmakologie
Medizinische Universität Wien
Outcome results
None listed