Nilotinib in Cognitively Impaired Parkinson Disease Patients 001

NCT ID: NCT02281474

Last Updated: 2015-12-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Nilotinib

Intervention Type: DRUG

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.

Group Type: ACTIVE_COMPARATOR

Nilotinib

Intervention Type: DRUG

Interventions

Nilotinib

Intervention Type: DRUG

Other Intervention Names

Tasigna

Eligibility 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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Georgetown University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

MedStar Georgetown University Hospital

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

Countries

United States

References

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 Jul 18:1-32. doi: 10.1080/1028415X.2025.2531356. Online ahead of print.

Reference Type: DERIVED

PMID: 40680102 (View on PubMed)

Other Identifiers

IIT-2014-001

Identifier Type: -

Identifier Source: org_study_id