NCT02947893

Impact of Nilotinib on Safety, Biomarkers and Clinical Outcomes in Mild to Moderate Alzheimer's Disease

A Randomized, Double Blind, Placebo-controlled Study to Evaluate the Impact of Low Doses of Nilotinib (Tasigna®) on Safety, Biomarkers and Clinical Outcomes in Subjects With Mild to Moderate Alzheimer's Disease

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 37 (actual)
• Sponsor: Georgetown University · Academic / Other
• Sex: All
• Age: 50 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

The investigators hypothesize that Nilotinib will be safe in individuals with mild to moderate AD. Specifically, investigators hypothesize that low daily oral doses of Nilotinib will lead to CSF penetration, CNS Abl inhibition, and stabilization of CSF total Tau and p-Tau231/181 and Abeta42/40 levels. The investigators hypothesize that Nilotinib will decrease brain load of amyloid using amyloid positron emission tomography (PET). The investigators also predict that Nilotinib will reduce CSF markers of cell death, including neuron specific enolase (NSE) and S100B.

Detailed description

The investigators propose a novel treatment strategy that involves Abl inhibition to alter Abeta40/42, total Tau and p-Tau231/181 in subjects with mild to moderate dementia due to AD. The investigators pre-clinical studies show that Nilotinib inhibits brain Abl, decreases Abeta and p-Tau, modulates brain and peripheral immune profiles and reverses cognitive decline in AD models. Taken together, these data support the hypothesis that Nilotinib is a viable therapeutic candidate - via Abl inhibition - in subjects with AD. Based on strong pre-clinical evidence about the effects of Nilotinib on neurodegenerative pathologies, including autophagic clearance of neurotoxic proteins, immunity and behavior, the investigators conducted an open label pilot clinical trial in advanced (stage 3-5) PD with dementia (PDD) and Lewy Body Dementia (LBD) patients. Participants (N=12) were randomized 1:1 to once daily oral dose of 150mg and 300mg Nilotinib for 6 months. The investigators showed that Nilotinib penetrates the blood brain barrier (BBB), in agreement with pre-clinical data. Several studies show that Abeta42 is decreased and CSF total Tau and p-Tau are increased in PD and LBD. Investigators data show that Nilotinib reverses loss of CSF Abeta40/42 and significantly reduces (N=5, P\<0.05) CSF total Tau and p-Tau between baseline and 6 months treatment. These biomarker changes are consistent with cognitive improvement (3.5-3.85 points) using Mini-Mental Status Exam (MMSE) and the Scales for Outcomes in Parkinson's Disease-Cognition (SCOPA-Cog) between baseline and 6 months. These data are very compelling to evaluate the effects of Nilotinib in a phase II, randomized, double-blind, placebo-controlled trial in patients with mild to moderate AD.

Conditions

• Alzheimer's Disease

Interventions

Type	Name	Description
DRUG	Placebo Capsule(s) Once a Day by Mouth	1 capsule of Placebo once a day for 6 months followed by 2 capsules of Placebo for another 6 months
DRUG	Nilotinib Capsule(s) Once a Day by Mouth	1 capsule of Nilotinib 150 mg once a day for 6 months followed by 2 capsules of Nilotinib (150 mg each capsule = 300 mb total) for the subsequent 6 months

Timeline

• Start date: 2017-01-01
• Primary completion: 2020-12-01
• Completion: 2021-03-01
• First posted: 2016-10-28
• Last updated: 2026-02-13

Locations

1 site across 1 country: United States