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Nilotinib in Huntington's Disease

NCT03764215 · Status: UNKNOWN · Phase: PHASE1 · Type: INTERVENTIONAL · Enrollment: 10

Last updated 2020-02-20

No results posted yet for this study

Summary

Based on strong pre-clinical evidence of the effects of Nilotinib on neurodegenerative pathologies, including autophagic clearance of neurotoxic proteins, neurotransmitters (dopamine and glutamate), immunity and behavior, the investigators conducted an open label pilot clinical trial in mid-to-advanced PD with dementia (PDD) and Dementia with Lewy Bodies (DLB) (stage 3-4) patients. Participants (N=12) were randomized 1:1 to once daily oral dose of 150mg and 300mg Nilotinib for 6 months. The investigators data suggests that Nilotinib penetrates the brain and inhibits CSF Abelson (Abl) activity via reduction of phosphorylated Abl in agreement with pre-clinical data. Several studies suggest that CSF alpha-Synuclein and Abeta42 are decreased and CSF total Tau and p-Tau are increased in PD and DLB. The investigators data shows attenuation of loss of CSF alpha-Synuclein and Abeta40/42 with 300mg (50% of the CML dose) compared to 150mg Nilotinib after 6 months treatment. CSF homovanillic acid (HVA), which is a by-product of dopamine metabolism, is significantly increased; and CSF total Tau and p-Tau are significantly reduced (N=5, P\<0.05) with 300mg Nilotinib between baseline and 6 months treatment. Despite the reduction of L-Dopa replacement therapies in our study, the Unified Parkinson's Disease Rating Scale (UDPRS) I-IV scores improved with 150mg (3.5 points) and 300mg (11 points) from baseline to 6 months and worsened (13.7 points and 11.4 points) after 3 months withdrawal of 150mg and 300mg, respectively. Other non-motor functions e.g. constipation was resolved in all patients and cognition was also improved (3.5 points) using both the Mini-Mental Status Exam (MMSE) or the Scales for Outcomes in Parkinson's Disease-Cognition (SCOPA-Cog) between baseline and 6 months. MMSE scores returned to baseline after 3 months of Nilotinib withdrawal. These data are very compelling to evaluate the effects of Nilotinib in an open label proof-of-concept study in patients with HD.

Conditions

  • Huntington Disease

Interventions

DRUG

Nilotinib 150 MG

10 participants will receive an oral dose of 150mg Nilotinib once daily for 3 months (group 1). If this dose is tolerated another 10 participants will receive an oral dose of 300mg Nilotinib once daily (group 2) for 3 months.

Sponsors & Collaborators

  • Georgetown University

    lead OTHER

Study Design

Purpose
TREATMENT
Masking
NONE
Model
SEQUENTIAL

Eligibility

Min Age
25 Years
Max Age
90 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2018-11-15
Primary Completion
2020-11-30
Completion
2020-11-30
FDA Drug
Yes

Countries

  • United States

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03764215 on ClinicalTrials.gov