Nilotinib in Cognitively Impaired Parkinson Disease Patients 001

NCT02281474 | Completed Phase 1 DMC

• 1 other identifier: IIT-2014-001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Parkinson's Disease; Parkinson's Disease Dementia; Diffuse Lewy Body Disease

Outcome Measures

Primary Outcomes (1)

• Change in α-synuclein and Tau concentrations in the CSF and serum of patients

  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 Outcomes (2)

• Determine nilotinib's efficacy by improvement in motor and non-motor symptoms

  6 months

• Safety and tolerability, as measured by number of Participants with Adverse Events

  6 months

Study Arms (2)

150mg dosing

ACTIVE COMPARATOR

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

300mg dosing

ACTIVE COMPARATOR

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

Interventions

Nilotinib DRUG

Also known as: Tasigna

150mg dosing; 300mg dosing

Eligibility Criteria

• Age: 40 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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).
• Written informed consent
• Capability and willingness to comply with the study related criteria
• Patients between the age of 40-90 y
• Diagnosis of PD according to the UK Brain Bank Diagnostic Criteria
• Early PD subjects with MMSE between 23-30.
• Hoehn and Yahr stage \<2
• Stable treatment (\>4 weeks) with MAO-B inhibitor (Selegeline up to 10mg/d or rasagiline up to 1 mg/d) allowable
• Patients not needing dopamine agonist or levodopa therapy presently or at least for the next 6 months
• Idiopathic PD with NO genetic mutations (autosomal recessive or dominant)
• Detectable levels of CSF for blood and CSF Alpha-Synuclein

You may not qualify if:

• Patients with a known genetic form of PD that does not involve alpha-synuclein.
• Unwillingness to undergo lumbar punctures
• Immeasurable CSF α-synuclein.
• Presence of dementia or severe cognitive impairment that would not permit the patient to give adequate feedback for potential side effects.
• Unwilling to be in an off state for UPDRS assessment.
• Pre-menopausal women
• Patients with autosomal recessive (PARKIN, PINK1 or DJ1) or dominant mutations (LRRK2)
• Patients with hypokalemia, hypomagnesaemia, or long QT syndrome.
• Concomitant drugs known to prolong the QT interval
• Strong CYP3A4 inhibitors
• Any drugs or foods that may interact with Nilotinib as stated in the Package Insert (PI).
• Medical history of liver and pancreatic diseases.
• 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.
• History of any cardiovascular disease, including hypertension, myocardial infraction or cardiac failure, angina, arrhythmia.

Sponsors & Collaborators

• Georgetown University: lead

Study Sites (1)

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Related Publications (1)

• Joshi D, Kulkarni M, Parekh P, Shah S, Greig NH, Acharya S. Targeting protein kinases in Parkinson's disease: the emerging role of phytoconstituents. Nutr Neurosci. 2025 Dec;28(12):1532-1563. doi: 10.1080/1028415X.2025.2531356. Epub 2025 Jul 18.

  PMID: 40680102 DERIVED

MeSH Terms

Conditions

Parkinson Disease; Lewy Body Disease

Interventions

nilotinib

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Dementia; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2014
• First Posted: November 3, 2014
• Study Start: November 1, 2014
• Primary Completion: May 1, 2015
• Last Updated: December 16, 2015

Record last verified: 2015-12

Locations

US (1)