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Nilotinib in Cognitively Impaired Parkinson Disease Patients 001

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ClinicalTrials.gov Identifier: NCT02281474
Recruitment Status : Completed
First Posted : November 2, 2014
Last Update Posted : December 16, 2015
Sponsor:
Information provided by (Responsible Party):
Georgetown University

Study Description
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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.

Condition or disease Intervention/treatment Phase
Parkinson's Disease Parkinson's Disease Dementia Diffuse Lewy Body Disease Drug: Nilotinib Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open Label Dose Escalation of Nilotinib in Cognitively Impaired Parkinson Disease Patients With Elevated Cerebrospinal Fluid and Blood α-Synuclein
Study Start Date : November 2014
Actual Primary Completion Date : May 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Nilotinib

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: 150mg dosing
This arm will take 150mg of Nilotinib by mouth daily for the 6 month drug period to establish a safe and efficacious dose.
 Drug: Nilotinib
Other Name: Tasigna
Active Comparator: 300mg dosing
This arm will take 300mg of Nilotinib by mouth daily for the 6 month drug period to establish a safe and efficacious dose.
 Drug: Nilotinib
Other Name: Tasigna


Outcome Measures
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Primary Outcome Measures :
  1. Change in α-synuclein and Tau concentrations in the CSF and serum of patients [ Time Frame: 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 Outcome Measures :
  1. Determine nilotinib's efficacy by improvement in motor and non-motor symptoms [ Time Frame: 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.


  2. Safety and tolerability, as measured by number of Participants with Adverse Events [ Time Frame: 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.



Eligibility Criteria
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Ages Eligible for Study:   40 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02281474


Locations
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United States, District of Columbia
MedStar Georgetown University Hospital
Washington, District of Columbia, United States, 20007
Sponsors and Collaborators
Georgetown University
More Information
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Responsible Party: Georgetown University
ClinicalTrials.gov Identifier: NCT02281474    
Other Study ID Numbers: IIT-2014-001
First Posted: November 2, 2014    Key Record Dates
Last Update Posted: December 16, 2015
Last Verified: December 2015
Additional relevant MeSH terms:
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Parkinson Disease
Lewy Body Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
 Movement Disorders
Synucleinopathies
Neurodegenerative Diseases
Dementia
Neurocognitive Disorders
Mental Disorders