Diffuse Lewy Body Disease, Parkinson's Disease, Parkinson's Disease Dementia
Conditions
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.
Interventions
DRUGNilotinib
Sponsors
Georgetown University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 90 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in α-synuclein and Tau concentrations in the CSF and serum of patients | 6 months | Working Hypothesis: PD patients have been shown to have elevated levels of α-synuclein in their CSF. Nilotinib has been shown to reduce α-synuclein and Tau in the gastrointestinal tract and central nervous system in animal models, and similarly, we propose will show changes in CSF and serum α-synuclein concentrations in nilotinib treated PD patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determine nilotinib's efficacy by improvement in motor and non-motor symptoms | 6 months | Working Hypothesis: By following strict safety guidelines, monitoring patients through physical examinations, self-examinations, laboratory and neurological examinations, nilotinib will be a safe drug to use in patients with PD and PD related patients. Determine if any clinical benefit is observed in this small, short, limited clinical trial. Working Hypothesis: In cell culture and animal models of PD, dopaminergic neurons have shown increased cell death with accumulating α-synuclein. Therefore, PD patients treated with nilotinib, which lowers α-synuclein and Tau in vivo and in vitro studies, will have improvement or stabilization of their motor UPDRS and cognition. |
| Safety and tolerability, as measured by number of Participants with Adverse Events | 6 months | Working Hypothesis: By following strict safety guidelines, monitoring patients through physical examinations, self-examinations, laboratory and neurological examinations, nilotinib will be a safe drug to use in patients with PD and PD related patients. Determine if any clinical benefit is observed in this small, short, limited clinical trial. Working Hypothesis: In cell culture and animal models of PD, dopaminergic neurons have shown increased cell death with accumulating α-synuclein. Therefore, PD patients treated with nilotinib, which lowers α-synuclein and Tau in vivo and in vitro studies, will have improvement or stabilization of their motor UPDRS and cognition. |
Countries
United States
Outcome results
None listed