Alzheimer Disease
Conditions
Keywords
Dopamine, Rotigotine
Brief summary
This is a 24-week prospective, randomized, double-blind, placebo-controlled, multi-center phase III study evaluating efficacy and safety of rotigotine 4mg/24 hrs in combination with rivastigmine 9.5 mg/24 hrs in mild to moderate AD patients. The total study duration per patient from baseline to the end will be 24 weeks. The study has a placebo-controlled design to eliminate experimental biases that arise from a participants' expectations, observer's effect on the participants, observer bias, confirmation bias, and other sources.
Detailed description
Patients will be screened at trial sites for determination of eligibility to enter the study on the basis of diagnostic evaluations, according to current diagnostic criteria for probable AD, and safety assessments (vital sign complete physical and neurological examinations). The efficacy assessments (cognitive/behavioral evaluations) will be performed at Baseline before starting treatment and repeated ontreatment at Weeks 6, 12 and 24. EEG neurophysiological examinations will be performed at Baseline and at Week 24. Plasma biomarkers will be collected at baseline and at Week 24. Visit windows are ±7 days for all the scheduled visits. At each in-clinic visit (or upon early termination), AEs will be recorded, at screening, baseline, weeks 6, 12 and 24 vital signs measured, and physical and neurological examination performed. During intervening times between visits, caregivers will be contacted by telephone at approximately at Weeks 4 and 16 and an unscheduled visit will take place if needed in response to a safety concern.
Interventions
Rotigotine 4 mg/24Hrs administration for 24 weeks
DRUGPlacebo
Placebo administration for 24 weeks
Sponsors
I.R.C.C.S. Fondazione Santa Lucia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Men and women (non-childbearing potential, as defined in Appendix 2) with a diagnosis of AD according to IWG criteria 2. Age 50-85 years 3. MRI or computerized tomography (CT) assessment, corroborating the clinical diagnosis of AD and excluding other potential causes of dementia, especially cerebrovascular lesions (see
Exclusion criteria
, number 3) 4. Patients who show CSF biomarker data supporting the diagnosis of AD (for Czech Republic only: lumbar punctures can be performed for screening purposes), or patients with a positive Amyloid Pet Scan will qualify for the study 5. Stable on a treatment with rivastigmine transdermal patch for at least 3 months, of which at least the last month was at 9.5mg/day, or for one month, if the patient had received donepezil before rivastigmine 6. Mild to moderate stage of AD according to MMSE ≥18 and ≤26 7. Clinical Dementia Rating (CDR) total score of 0.5 or 1 (mild) 8. Evidence of frontal lobe dysfunctions as assessed by FAB ≤14 9. Absence of major depressive disease according to GDS of \< 5 10. Formal education for five or more years 11. Previous decline in cognition for more than six months as documented in patient medical records 12. A caregiver available and living in the same household or interacting with the patient and available if necessary to assure administration of drug 13. Patients living at home or nursing home setting without continuous nursing care 14. General health status acceptable for a participation in a 6-month clinical trial 15. Stable pharmacological treatment of any other chronic condition for at least one month prior to screening 16. No regular intake of prohibited medications 17. Signed informed consent by the patient. If there are any doubts that the patient is mentally capable of giving informed consent, the patient will be examined and verified to be mentally capable by an independent physician/ neurologist, prior to the initiation of any study specific procedure. Signed consent of the caregiver
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline to Week 24 in the FAB to evaluate efficacy of rotigotine in combination with rivastigmine on frontal lobe cognitive functions as compared to rivastigmine in combination with placebo. | From enrollment to the end of 24 weeks of treatment | FAB is a brief battery of six neuropsychological tasks designed to assess frontal lobe function |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline to Week 24 in the ADCS-ADL to evaluate efficacy of rotigotine in combination with rivastigmine on autonomies of daily living as compared to rivastigmine in combination with placebo | From enrollment to the end of 24 weeks of treatment | The ADCS-ADL includes 23 items that were derived from a larger set of items describing performance of activities of daily living |
| Change from Baseline to Week 24 in the MoCA to evaluate efficacy of rotigotine in combination with rivastigmine on cognition as compared to rivastigmine in combination with placebo. | From enrollment to the end of 24 weeks of treatment | The MoCA is a brief, simple, and reliable screening test for AD. The test checks language, memory, visual and spatial thinking, reasoning, and orientation skills. |
| Change from Baseline to Week 24 in the CDR-SOB, to evaluate efficacy of rotigotine in combination with rivastigmine on cognition as compared to rivastigmine in combination with placebo | From enrollment to the end of 24 weeks of treatment | The CDR is a 5-point scale used to characterize six domains of cognitive and functional performance applicable to AD and related dementias: Memory, Orientation, Judgment & Problem Solving, Community Affairs, Home & Hobbies, and Personal Care |
| Change from Baseline to Week 24 in the ADAS-Cog14 to evaluate efficacy of rotigotine in combination with rivastigmine on memory functions as compared to rivastigmine in combination with placebo. | From enrollment to the end of 24 weeks of treatment | ADAS-cog assesses the level of cognitive dysfunction in AD. The ADAS-Cog14 consists of items from the following areas chosen for their sensitivity to AD: language; memory; praxis executive functions and orientation. |
| Change from Baseline to Week 24 in the AMI to evaluate efficacy of rotigotine in combination with rivastigmine on levels of apathy and motivation as compared to rivastigmine in combination with placebo. | From enrollment to the end of 24 weeks of treatment | The Apathy-Motivation Index was developed as a brief self-report index of apathy and motivation. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline to Week 24 in the EEG recordings, to evaluate effects of rotigotine in combination with rivastigmine or rivastigmine in combination with placebo on cortical oscillatory activity. | From enrollment to the end of 24 weeks of treatment | All patients will undergo resting EEG recordings at the beginning and at the end of the experimental protocol with a 21 channels EEG. The neurophysiological measurement will be performed with the eyes closed and will last 3 minutes. |
| Change from Baseline to Week 24 in plasma Neurofilament light chain (NfL) and Aβ42 and p-tau concentrations to evaluate effects of rotigotine in combination with rivastigmine in combination with placebo on plasma biomarkers | From enrollment to the end of 24 weeks of treatment | Plasma samples will be collected according to the trail schedule |
Countries
Italy
Contacts
Primary ContactGiacomo Koch, Prof
Outcome results
None listed