Open Label Dose Escalation of Nilotinib in Cognitively Impaired Parkinson Disease Patients With Elevated Cerebrospinal Fluid and Blood α-Synuclein

Nilotinib in Cognitively Impaired Parkinson Disease Patients 001

Sponsors

Lead sponsor: Georgetown University

Source Georgetown University
Brief Summary

This pilot study will test Nilotinib's ability to alter the abnormal protein build up in Parkinson disease and Diffuse Lewey Body Disease patients . Patients will receive Nilotinib at different doses for 6 months. Patients will then be tested to see if there is change in three areas: 1) has the disease symptoms changed. 2) has levels of a specific misfolded protein changed in the fluid around their brain and spine. 3) Have inflammatory markers changed in the patient's blood and fluid around their brain and spine. If successful, this drug could be used to slow down or stop the progression of disorders that involve abnormal collection of misfolded proteins. However, the main purpose of this pilot study is to check for the safety of using this medication at this level.

Overall Status Completed
Start Date November 2014
Primary Completion Date May 2015
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Change in α-synuclein and Tau concentrations in the CSF and serum of patients 6 months
Secondary Outcome
Measure Time Frame
Determine nilotinib's efficacy by improvement in motor and non-motor symptoms 6 months
Safety and tolerability, as measured by number of Participants with Adverse Events 6 months
Enrollment 12
Condition
Intervention

Intervention type: Drug

Intervention name: Nilotinib

Other name: Tasigna

Eligibility

Criteria:

Inclusion Criteria:

1. Patients aged 40 to 90 with Idiopathic Parkinson's Disease (Significant Sinemet response) on a stable medication drug regimen L-dopa and/or Dopamine agonist (at least 1 month before enrollment with no new medication change) and with moderate to severe cognitive impairment (MOCA ≤24).

Inclusions criteria:

1. Written informed consent

2. Capability and willingness to comply with the study related criteria

3. Patients between the age of 40-90 y

4. Diagnosis of PD according to the UK Brain Bank Diagnostic Criteria

5. Early PD subjects with MMSE between 23-30.

6. Hoehn and Yahr stage <2

7. Stable treatment (>4 weeks) with MAO-B inhibitor (Selegeline up to 10mg/d or rasagiline up to 1 mg/d) allowable

8. Patients not needing dopamine agonist or levodopa therapy presently or at least for the next 6 months

9. Idiopathic PD with NO genetic mutations (autosomal recessive or dominant)

10. Detectable levels of CSF for blood and CSF Alpha-Synuclein

Exclusion Criteria:

1. Patients with a known genetic form of PD that does not involve alpha-synuclein.

2. Unwillingness to undergo lumbar punctures

3. Immeasurable CSF α-synuclein.

4. Presence of dementia or severe cognitive impairment that would not permit the patient to give adequate feedback for potential side effects.

5. Unwilling to be in an off state for UPDRS assessment.

6. Pre-menopausal women

7. Patients with autosomal recessive (PARKIN, PINK1 or DJ1) or dominant mutations (LRRK2)

8. Patients with hypokalemia, hypomagnesaemia, or long QT syndrome.

9. Concomitant drugs known to prolong the QT interval

10. Strong CYP3A4 inhibitors

11. Any drugs or foods that may interact with Nilotinib as stated in the Package Insert (PI).

12. Medical history of liver and pancreatic diseases.

13. Clinical signs indicating syndromes other than idiopathic PD, including supranucelar gaze palsy, signs of frontal dementia, history of stroke, head injury or encephalitis, cerebellar sings, early severe autonomic involvement, Babinski's signs.

14. History of any cardiovascular disease, including hypertension, myocardial infraction or cardiac failure, angina, arrhythmia.

Gender: All

Minimum age: 40 Years

Maximum age: 90 Years

Healthy volunteers: Accepts Healthy Volunteers

Location
facility MedStar Georgetown University Hospital
Location Countries

United States

Verification Date

December 2015

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: 150mg dosing

Arm group type: Active Comparator

Description: This arm will take 150mg of Nilotinib by mouth daily for the 6 month drug period to establish a safe and efficacious dose.

Arm group label: 300mg dosing

Arm group type: Active Comparator

Description: This arm will take 300mg of Nilotinib by mouth daily for the 6 month drug period to establish a safe and efficacious dose.

Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov