A Pilot Trial of Lithium in Subjects With Progressive Supranuclear Palsy or Corticobasal Degeneration
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 17
- 试验地点
- 9
- 主要终点
- Ability to Tolerate Lithium Carbonate
研究概览
简要总结
The goal of this trial is to evaluate the safety and tolerability of lithium in people with progressive supranuclear palsy or corticobasal degeneration.
详细描述
Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are progressive, adult-onset neurodegenerative disorders characterized by the accumulation of hyperphosphorylated tau. Symptomatic treatment is of minimal benefit to individuals with PSP or CBD, and there are no effective disease modifying agents.
Tau phosphorylation is regulated in part by the enzyme GSK-3β (glycogen synthase kinase-3 beta ). Inhibition of this enzyme may benefit individuals with PSP or CBD by decreasing the levels of phosphorylated tau. Lithium is known to inhibit GSK-3β and, thus, may be a rational therapeutic approach.
The primary objective of this study is to determine the safety and tolerability of lithium in people with PSP or CBD. Additionally, this study will evaluate potential biomarkers and clinical outcome measures as well as assess study drug compliance.
In this multicenter, open label study, 45 eligible participants with PSP or CBD will receive the study drug, lithium. The dosage of lithium will be titrated over a 5-week period, and participants will then be followed prospectively for 6 months. Participants will be evaluated at the screening visit, baseline visit, and weeks 2 and 5 during the titration phase. Clinic study visits will then occur on alternate months through week 28. Telephone visits will occur between clinic study visits.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to give informed consent
- •Able to comply with the study protocol, including ability to attend follow-up study visits for the duration of the study
- •Diagnosis of PSP or CBD based on the following criteria:
- •Probable PSP:
- •Gradually progressive akinetic disorder
- •Unequivocal and prominent slowing of vertical saccades or vertical supranuclear gaze palsy
- •Early prominent postural instability or early falls
- •Poor or absent response to levodopa
- •Probable CBD:
- •Chronic progressive course
- •Asymmetric onset
- •Presence of higher cortical dysfunction (apraxia, apraxia of speech, non-fluent aphasia, cortical sensory loss, or alien limb)
- •Movement disorder: rigid/akinetic syndrome resistant to levodopa and either dystonic limb posturing or focal myoclonus in limb (spontaneous or stimulus sensitive)
- •If psychotropic or anti-parkinsonian medications are taken (e.g., anxiolytics, hypnotics, benzodiazepines, antidepressants, levodopa, amantadine), the dosage must be stable for 28 days prior to the screening visit and should be maintained at constant dosages throughout the study, as possible
- •If NSAIDs, ACE-Is, ARBs, thiazide diuretics, COX-2 inhibitors or theophylline are taken by the subject, the dosage must be stable for 28 days prior to the screening visit and should be maintained at constant dosages throughout the study, as possible.
- •Creatinine clearance > 50 ml/min
- •Able to take oral medication
- •Women must not be able to become pregnant (e.g., post menopausal, surgically sterile or using adequate birth control methods for the duration of the study.)
- •Able to identify a study partner
排除标准
- •Evidence of other diseases that could explain the clinical presentation
- •History of known sensitivity or intolerability to lithium or to other known ingredients in the study drug
- •Exposure to any investigational agent within 28 days of the screening visit
- •Clinically significant cardiac disease or EKG findings
- •Other serious illness, including psychiatric illness ("serious illness" is defined as an illness that is unstable enough that it might jeopardize the subject's ability to complete the study)
- •Moderate to severe ongoing depression
- •Family history of "PSP" or "CBS"
- •Clinically significant abnormalities on the screening visit laboratory results
- •Any AE ≥ Grade 3 as listed on the CTCAE, version 3.0
- •Women who are pregnant or breastfeeding
- •History of brain surgery
- •Use of other potential GSK-3β inhibitors (e.g., valproic acid)
- •Use of iodide salts [e.g., calcium iodide, hydrogen iodide (hydriodic acid), iodide, iodinated glycerol (Organidin), iodine, potassium iodide (SSKI), and sodium iodide]
- •Previous use of lithium
- •Use of Coenzyme Q10 at a dosage greater than 600 mg a day or NanoQuinon at a dosage greater than 150mg a day or 2.5 mg/kg a day
- •Active psoriasis
研究组 & 干预措施
1
All participants will receive lithium. The dosage will be titrated over a 5-week period. Participants will then be followed prospectively for 6 months. Participants will be evaluated at the screening visit, baseline visit, and weeks 2 and 5 during the titration phase. Clinic study visits will then occur on alternate months through week 28. Telephone visits will occur between clinic study visits.
干预措施: Lithium (Drug)
结局指标
主要结局
Ability to Tolerate Lithium Carbonate
时间窗: 28 weeks
The ability to complete the study period on lithium at a serum concentration of at least 0.4 mEq/L.
次要结局
- Study Drug Compliance(28 weeks)
- Changes in Amount of Tau and Phosphorylated Tau in Cerebral Spinal Fluid (CSF)(28 weeks)
- Change in Brain-Derived Neurotrophic Factor (BDNF) in CSF(28 weeks)
- Change in Glycogen Synthase Kinase (GSK)-3 Beta Activity(28 weeks)
- PSP Rating Scale Score: Change From Baseline(28 weeks)
- Unified Parkinson Disease Rating Scale (UPDRS) Motor Subscale Score: Change From Baseline(28 weeks)
- PSP-Quality of Life Scale (QoL):Change From Baseline(28 weeks)
- Frontal Assessment Battery (FAB): Change From Baseline(28 weeks)
- Geriatric Depression Scale(GDS)-15:Change From Baseline(28 weeks)