Alzheimer's disease (AD) and mild cognitive impairment (MCI) MedDRA version: 20.0 Level: HLT Classification code 10001897 Term: Alzheimer's disease (incl subtypes) System Organ Class: 100000004852
Conditions
Interventions
Trade Name: Rapamune
Pharmaceutical Form: Tablet
Sponsors
Karolinska Institutet
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • The subject is capable of giving, and has the capacity to give, informed consent. • The subject has availability of a responsible study partner who can accompany the subject to all planned visits • The subject and the responsible study partner have given written consent to participate in the study • The subject is male or female between 50 and 80 years • The subject has a clinical diagnosis of MCI or dementia of Alzheimer's type. • For subjects with a diagnosis of MCI, evidence for underlying AD pathology within 2 years prior to screening is present, according to: o Cerebrospinal fluid (CSF) beta amyloid 1-42/1-40x10 ratio4 words after 30 minutes • The subject has normal or clinically acceptable medical history, physical examination, and vital signs Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 5 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: • History of any major disease that may interfere with safe engagement in the intervention (especially severe liver or kidney disease, or uncontrolled diabetes). • History of a major neurological disorder, central nervous system infarct, infection, or focal lesions of clinical significance on MRI scans. • The subject fulfills any contraindication for the use of sirolimus as per the summary of product characteristics • Significant obesity, per the investigator's judgement • Untreated hyperlipidemia that is clinically significant, per the investigator's judgment • Treatment with immunosuppressive medications within the last 90 days (topical and nasal corticosteroids and inhaled corticosteroids for asthma are permitted), or chemotherapeutic agents for malignancy within the last 3 years • The subject has had major surgery within 3 months prior to the planned start of sirolimus treatment, OR has major surgery planned during the period of the trial. • Use of experimental medications for AD or any other investigational medication or device within 60 days. Participants who have been involved in a monoclonal antibody study are excluded unless it is known that they were receiving placebo in that trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of sirolimus in patients suffering from MCI or early-stage AD.;Secondary Objective: To evaluate the safety and tolerability of sirolimus when intermittently dosed in MCI/AD patients To evaluate the pharmacokinetic properties of intermittent dosing of sirolimus Exploratory objectives: To evaluate the effect of sirolimus on age-related pathological processes in the human body ;Primary end point(s): Change-from-baseline for 18F labeled fluorodeoxyglucose ([18F]FDG) cerebral uptake, measured with positron emission tomography (PET) ;Timepoint(s) of evaluation of this end point: Baseline [18F]FDG PET will be done within six week of start of treatment with sirolimus. Follow up PET at earliest two weeks prior to last dose of sirolimus, at latest four weeks after the last dose. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change-from-baseline for: • CSF levels of AD markers • Neuropsychological tests • Safety and tolerability as measured by incidence of AEs/ SAEs; clinical laboratory test data; vital signs • Pharmacokinetic properties of intermittent dosing of sirolimus: Cmin, Cmax, AUC ;Timepoint(s) of evaluation of this end point: Lumbar puncture and cognitive testing will be done prior to initiation of sirolimus treatment with follow-up measurements at the earliest two weeks prior to the last dose of sirolimus, at the latest four weeks after the last dose. Pharmacokinetic tests will be done around week 13 after initiation of sirolimus treatment (halfway through the treatment period) Data on safety and tolerability will be collected continuously throughout the trial. | — |
Countries
Sweden
Contacts
Public ContactBrain Molecular Imaging Centre
Karolinska Institutet
Outcome results
None listed