Nilotinib in Cognitively Impaired Parkinson Disease Patients 001

• Register: ClinicalTrials.gov
• Last refreshed on: 28 December 2015
• Main ID: NCT02281474
• Date of registration: 27/10/2014
• Prospective Registration: Yes
• Primary sponsor: Georgetown University
• Public title: Nilotinib in Cognitively Impaired Parkinson Disease Patients 001
• Scientific title: Open Label Dose Escalation of Nilotinib in Cognitively Impaired Parkinson Disease Patients With Elevated Cerebrospinal Fluid and Blood a-Synuclein
• Date of first enrolment: November 2014
• Target sample size: 12
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02281474
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

United States

Key inclusion & exclusion 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 a-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.



Age minimum: 40 Years
Age maximum: 90 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Diffuse Lewy Body Disease

Parkinson's Disease

Parkinson's Disease Dementia

Intervention(s)

Drug: Nilotinib

Primary Outcome(s)

Change in a-synuclein and Tau concentrations in the CSF and serum of patients [Time Frame: 6 months]

Secondary Outcome(s)

Safety and tolerability, as measured by number of Participants with Adverse Events [Time Frame: 6 months]

Determine nilotinib's efficacy by improvement in motor and non-motor symptoms [Time Frame: 6 months]

Secondary ID(s)

IIT-2014-001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors