A Randomized, Double Blind, Placebo-controlled Study to Evaluate the Impact of Nilotinib Treatment on Safety, Tolerability, Pharmacokinetics and Biomarkers in Dementia With Lewy Bodies (DLB)
Dementia with Lewy Bodies (DLB) is an alphasynucleinopathy and the second most common form of dementia in the elderly. DLB shares striking neuropathological and clinical similarities with both Parkinson's disease (PD) and Alzheimer's disease (AD). Nilotinib (Tasigna®, AMN107, Novartis, Switzerland) is approved by the FDA and is well tolerated for CML treatment at oral doses of 600-800mg daily. The Investigators propose to perform a phase II randomized, double blinded, placebo controlled study to evaluate the impact of Nilotinib in patients with DLB.
• Written informed consent
• Capable of providing informed consent and complying with study procedures. Subjects who are unable to provide consent may use a Legally Authorized Representative (LAR).
• Clinical diagnosis of DLB according to McKeith et al (7) with both dementia MoCA≥18 and Parkinsonian defined as bradykinesia in combination with rest tremor, rigidity or both UPDRS I-III is less than 50 and/or UPDRS-III between 15 -40 on-state. Dementia and Parkinsonism must be present with at least one other symptom such as fluctuation, visual hallucinations or REM sleep behavioral disorder (RBD)
• 2.5 ≥Hoehn and Yahr stage ≤3
• MDS-UPDRS-III 15-40 on-state (or up to 70 on the off state)
• Abnormal DaTScan
• Stable concomitant medical and/or psychiatric illnesses in the judgement of the PI
• Patients between the age of 25-90 years, medically stable
• Must NOT be stable on mono-amine oxidase (MAO)-B inhibitors (Selegeline or rasagiline) for at least 4 weeks before enrollment and during Nilotinib treatment.
⁃ Must be medically stable on less than or equal to 800mg Levodopa daily for at least 4 weeks
⁃ QTc interval 350-460 ms, inclusive
⁃ Participants must be willing to undergo LP at baseline and 6 months after treatment