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Nilotinib in Cognitively Impaired Parkinson Disease Patients 001

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE October 27, 2014
First Posted Date  ICMJE November 2, 2014
Last Update Posted Date December 16, 2015
Study Start Date  ICMJE November 2014
Actual Primary Completion Date May 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 30, 2014)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 30, 2014)
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nilotinib in Cognitively Impaired Parkinson Disease Patients 001
Official Title  ICMJE Open Label Dose Escalation of Nilotinib in Cognitively Impaired Parkinson Disease Patients With Elevated Cerebrospinal Fluid and Blood α-Synuclein
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Parkinson's Disease
  • Parkinson's Disease Dementia
  • Diffuse Lewy Body Disease
Intervention  ICMJE Drug: Nilotinib
Other Name: Tasigna
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Nilotinib
  • 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.
    Intervention: Drug: Nilotinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 15, 2015)
12
Original Estimated Enrollment  ICMJE
 (submitted: October 30, 2014)
36
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date May 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02281474
Other Study ID Numbers  ICMJE IIT-2014-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Georgetown University
Study Sponsor  ICMJE Georgetown University
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Georgetown University
Verification Date December 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP