Brief Title
A Pilot Trial of Lithium in Subjects With Progressive Supranuclear Palsy or Corticobasal Degeneration
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 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.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Ability to Tolerate Lithium Carbonate
Secondary Outcome
Study Drug Compliance
Condition
Progressive Supranuclear Palsy
Intervention
Lithium
Study Arms / Comparison Groups
1
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
17
Start Date
September 2008
Completion Date
January 2010
Primary Completion Date
January 2010
Eligibility 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
Gender
All
Ages
40 Years - 80 Years
Accepts Healthy Volunteers
No
Contacts
Renè Gonin, PhD, ,
Location Countries
United Kingdom
Location Countries
United Kingdom
Administrative Informations
NCT ID
NCT00703677
Organization ID
NPTUNE_PSP_CBD
Secondary IDs
HHSN265200423611C
Responsible Party
Sponsor
Study Sponsor
Westat
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
Study Sponsor
Renè Gonin, PhD, Principal Investigator, (Math. Stats.), Westat
Verification Date
June 2015