A Pilot Trial of Lithium in Subjects With Progressive Supranuclear Palsy or Corticobasal Degeneration
Overview
- Phase
- Phase 1
- Intervention
- Lithium
- Conditions
- Progressive Supranuclear Palsy
- Sponsor
- Westat
- Enrollment
- 17
- Locations
- 9
- Primary Endpoint
- Ability to Tolerate Lithium Carbonate
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The goal of this trial is to evaluate the safety and tolerability of lithium in people with progressive supranuclear palsy or corticobasal degeneration.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
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.
Intervention: Lithium
Outcomes
Primary Outcomes
Ability to Tolerate Lithium Carbonate
Time Frame: 28 weeks
The ability to complete the study period on lithium at a serum concentration of at least 0.4 mEq/L.
Secondary Outcomes
- 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)