Open Label Dose Escalation of Nilotinib in Cognitively Impaired Parkinson Disease Patients With Elevated Cerebrospinal Fluid and Blood α-Synuclein
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Change in α-synuclein and Tau concentrations in the CSF and serum of patients
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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:
- •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-
- •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
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Nilotinib (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.
干预措施: Nilotinib (Drug)
结局指标
主要结局
Change in α-synuclein and Tau concentrations in the CSF and serum of patients
时间窗: 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.
次要结局
- 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)