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

Information source: Westat
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Progressive Supranuclear Palsy; Corticobasal Degeneration

Intervention: Lithium (Drug)

Phase: Phase 1/Phase 2

Status: Completed

Sponsored by: Westat

Official(s) and/or principal investigator(s):
Renè Gonin, PhD, Principal Investigator, Affiliation: (Math. Stats.), Westat

Summary

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

Clinical Details

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

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Ability to Tolerate Lithium Carbonate

Secondary outcome:

Study Drug Compliance

Changes in Amount of Tau and Phosphorylated Tau in Cerebral Spinal Fluid (CSF)

Change in Brain-Derived Neurotrophic Factor (BDNF) in CSF

Change in Glycogen Synthase Kinase (GSK)-3 Beta Activity

PSP Rating Scale Score: Change From Baseline

Unified Parkinson Disease Rating Scale (UPDRS) Motor Subscale Score: Change From Baseline

PSP-Quality of Life Scale (QoL):Change From Baseline

Frontal Assessment Battery (FAB): Change From Baseline

Geriatric Depression Scale(GDS)-15:Change From Baseline

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.

Eligibility

Minimum age: 40 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

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-3β 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

Locations and Contacts

Newcastle University, Newcastle upon Tyne NE4 5PL, United Kingdom

Northwestern University, Chicago, Illinois 60611, United States

Rush University Medical Center, Chicago, Illinois 60612, United States

University of Louisville, Louisville, Kentucky 40202, United States

University of Maryland, Baltimore, Maryland 21201, United States

UMDNJ Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901, United States

Beth Israel Medical Center, New York, New York 10003, United States

Oregon Health & Science University, Portland, Oregon 97239-3098, United States

Medical University of South Carolina, Charleston, South Carolina 29401, United States

Additional Information

Starting date: September 2008
Last updated: June 9, 2015

Page last updated: August 23, 2015

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