Clinical Trial: A Pilot Trial of Lithium in Subjects With Progressive Supranuclear Palsy or Corticobasal Degeneration

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Pilot Trial of Lithium in Subjects With Progressive Supranuclear Palsy or Corticobasal Degeneration

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 Summary:

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.


Sponsor: Westat

Current Primary Outcome: 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.


Original Primary Outcome: The ability to complete the study period on lithium at a serum concentration of at least 0.4 mEq/L [ Time Frame: 5-week titration phase followed by 6 months of treatment ]

Current Secondary Outcome:

  • Study Drug Compliance [ Time Frame: 28 weeks ]
    Subjects receiving 80% or more of the prescribed doses between study visits were considered compliant.
  • Changes in Amount of Tau and Phosphorylated Tau in Cerebral Spinal Fluid (CSF) [ Time Frame: 28 weeks ]
    Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are characterized by hyperphosphorylation of tau. Lithium inhibits one of the kinases (GSK-3 beta) that phosphorylates tau; levels of tau phosphorylation will be measured at baseline and at Week 28.
  • Change in Brain-Derived Neurotrophic Factor (BDNF) in CSF [ Time Frame: 28 weeks ]
    With inhibition of Glycogen Synthase Kinase (GSK)-3 beta, levels of BDNF may increase. BDNF levels will be measured at baseline and at Week 28.
  • Change in Glycogen Synthase Kinase (GSK)-3 Beta Activity [ Time Frame: 28 weeks ]
    Levels of beta-catenin and the ratio of phosphorylated GSK-3 beta to total GSK-3 beta will be measured at baseline and at Week 28
  • PSP Rating Scale Score: Change From Baseline [ Time Frame: 28 weeks ]
    The PSP Rating Scale is a 28-item scale designed to assess the disability associated with PSP. The six functional categories assessed are: daily activities, behavior, bulbar function, oculomotor function, limb motor function, and gait/midline function. Subjects will be assessed at baseline and Weeks 12, 20, and 28.
  • Unified Parkinson Disease Rating Scale (UPDRS) Motor Subscale Score: Change From Baseline [ Time Frame: 28 weeks ]
    The UPDRS is a commonly used clinical rating scale to assess motor function in patients with parkinsonism. Subjects will be assessed at baseline and Weeks 5, 12, 20, and 28.
  • PSP-Quality of Life Scale (QoL):Change From Baseline [ Time Frame: 28 weeks ]
    The PSP-QoL Scale is an instrument designed to assess mental and physical aspects of quality of life specifically in patients with PSP. Subjects will be assessed at baseline and Weeks 12, 20, and 28.
  • Frontal Assessment Battery (FAB): Change From Baseline [ Time Frame: 28 weeks ]
    The FAB is a brief, 6-item instrument designed to assess executive function. Subjects will be assessed at baseline and at Week 28.
  • Geriatric Depression Scale(GDS)-15:Change From Baseline [ Time Frame: 28 weeks ]
    The GDS-15 is a 15-item instrument used to screen for depression in the elderly. Subjects will be assessed at the Screening Visit and at Week 28.


Original Secondary Outcome:

  • Study drug compliance; effects of lithium on tau phosphorylation in cerebral spinal fluid; effects of lithium on GSK-3β activity [ Time Frame: 5-week titration phase followed by 6 months of treatment ]
  • clinical measures including PSP Rating Scale, Unified Parkinson Disease Rating Scale Motor Subscale, PSP-Quality of Life Scale, Frontal Assessment Battery, Geriatric Depression Scale-15 [ Time Frame: 5-week titration phase followed by 6 months of treatment ]


Information By: Westat

Dates:
Date Received: June 20, 2008
Date Started: September 2008
Date Completion:
Last Updated: June 9, 2015
Last Verified: June 2015