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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00703677
Other study ID # NPTUNE_PSP_CBD
Secondary ID HHSN265200423611
Status Completed
Phase Phase 1/Phase 2
First received
Last updated
Start date September 2008
Est. completion date January 2010

Study information

Verified date April 2024
Source Westat
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The goal of this trial is to evaluate the safety and tolerability of lithium in people with progressive supranuclear palsy or corticobasal degeneration.


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.


Recruitment information / eligibility

Status Completed
Enrollment 17
Est. completion date January 2010
Est. primary completion date January 2010
Accepts healthy volunteers No
Gender All
Age group 40 Years to 80 Years
Eligibility Inclusion Criteria: 1. Able to give informed consent 2. Able to comply with the study protocol, including ability to attend follow-up study visits for the duration of the study 3. Diagnosis of PSP or CBD based on the following criteria: 1. 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 2. 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) 4. 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 5. 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. 6. Creatinine clearance > 50 ml/min 7. Able to take oral medication 8. 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.) 9. Able to identify a study partner Exclusion Criteria: 1. Evidence of other diseases that could explain the clinical presentation 2. History of known sensitivity or intolerability to lithium or to other known ingredients in the study drug 3. Exposure to any investigational agent within 28 days of the screening visit 4. Clinically significant cardiac disease or EKG findings 5. 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) 6. Moderate to severe ongoing depression 7. Family history of "PSP" or "CBS" 8. Clinically significant abnormalities on the screening visit laboratory results 9. Any AE = Grade 3 as listed on the CTCAE, version 3.0 10. Women who are pregnant or breastfeeding 11. History of brain surgery 12. Use of other potential GSK-3ß inhibitors (e.g., valproic acid) 13. Use of iodide salts [e.g., calcium iodide, hydrogen iodide (hydriodic acid), iodide, iodinated glycerol (Organidin), iodine, potassium iodide (SSKI), and sodium iodide] 14. Previous use of lithium 15. 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 16. Active psoriasis

Study Design


Intervention

Drug:
Lithium
All participants will receive lithium. The dosage will be titrated over a 5-week period and then continued for an additional 6 months.

Locations

Country Name City State
United Kingdom Newcastle University Newcastle upon Tyne
United States University of Maryland Baltimore Maryland
United States Medical University of South Carolina Charleston South Carolina
United States Northwestern University Chicago Illinois
United States Rush University Medical Center Chicago Illinois
United States University of Louisville Louisville Kentucky
United States UMDNJ Robert Wood Johnson Medical School New Brunswick New Jersey
United States Beth Israel Medical Center New York New York
United States Oregon Health & Science University Portland Oregon

Sponsors (2)

Lead Sponsor Collaborator
Westat National Institute of Neurological Disorders and Stroke (NINDS)

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Ability to Tolerate Lithium Carbonate The ability to complete the study period on lithium at a serum concentration of at least 0.4 mEq/L. 28 weeks
Secondary Study Drug Compliance Subjects receiving 80% or more of the prescribed doses between study visits were considered compliant. 28 weeks
Secondary Changes in Amount of Tau and Phosphorylated Tau in Cerebral Spinal Fluid (CSF) 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. 28 weeks
Secondary Change in Brain-Derived Neurotrophic Factor (BDNF) in CSF 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. 28 weeks
Secondary Change in Glycogen Synthase Kinase (GSK)-3 Beta Activity 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 28 weeks
Secondary PSP Rating Scale Score: Change From Baseline 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. 28 weeks
Secondary Unified Parkinson Disease Rating Scale (UPDRS) Motor Subscale Score: Change From Baseline 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. 28 weeks
Secondary PSP-Quality of Life Scale (QoL):Change From Baseline 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. 28 weeks
Secondary Frontal Assessment Battery (FAB): Change From Baseline The FAB is a brief, 6-item instrument designed to assess executive function. Subjects will be assessed at baseline and at Week 28. 28 weeks
Secondary Geriatric Depression Scale(GDS)-15:Change From Baseline 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. 28 weeks
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