Clinical trial NCT02281474: Nilotinib in Cognitively Impaired Parkinson Disease Patients 001
Official title: Open Label Dose Escalation of Nilotinib in Cognitively Impaired Parkinson Disease Patients With Elevated Cerebrospinal Fluid and Blood α-Synuclein
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Parkinson's Disease
Parkinson's Disease Dementia
Diffuse Lewy Body Disease
Lead sponsor: Georgetown University
Sponsor class: OTHER
First posted: 2014-11-02
Enrollment: 12
Sex: ALL
Minimum age (years): 40
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Change in α-synuclein and Tau concentrations in the CSF and serum of patients
timeFrame: 6 months
Secondary outcomes:
measure: Determine nilotinib's efficacy by improvement in motor and non-motor symptoms
timeFrame: 6 months
measure: Safety and tolerability, as measured by number of Participants with Adverse Events
timeFrame: 6 months
Other outcomes:
Locations:
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
Study officials:
References: