Nilotinib in Cognitively Impaired Parkinson Disease Patients 001

December 15, 2015 updated by: Georgetown University

Open Label Dose Escalation of Nilotinib in Cognitively Impaired Parkinson Disease Patients With Elevated Cerebrospinal Fluid and Blood α-Synuclein

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • MedStar Georgetown University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • Tasigna

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
6 months
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.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Georgetown University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2014

Primary Completion (Actual)

May 1, 2015

Study Registration Dates

First Submitted

October 27, 2014

First Submitted That Met QC Criteria

October 30, 2014

First Posted (Estimate)

November 2, 2014

Study Record Updates

Last Update Posted (Estimate)

December 16, 2015

Last Update Submitted That Met QC Criteria

December 15, 2015

Last Verified

December 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IIT-2014-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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