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

NCT00703677 | Completed Phase 1 Results

• 2 other identifiers: NPTUNE_PSP_CBDHHSN265200423611C
• Study Type: interventional
• Target: 17
• Locations: 2 countries
• Sites: 9

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.

Conditions

Progressive Supranuclear Palsy; Corticobasal Degeneration

Keywords

progressive supranuclear palsy; corticobasal degeneration; PSP; CBD; lithium; tau

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• 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

Study Arms (1)

1

OTHER

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.

Drug: Lithium

Interventions

Lithium DRUG

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

1

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)
• 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
• 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.

You may not qualify if:

• 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
• History of brain surgery
• Use of other potential GSK-3β inhibitors (e.g., valproic acid)
• Use of iodide salts \[e.g., calcium iodide, hydrogen iodide (hydriodic acid), iodide, iodinated glycerol (Organidin), iodine, potassium iodide (SSKI), and sodium iodide\]
• Previous use of lithium
• 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

Sponsors & Collaborators

• Westat: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (9)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

UMDNJ Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08901, United States

Location

Beth Israel Medical Center

New York, New York, 10003, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239-3098, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29401, United States

Location

Newcastle University

Newcastle upon Tyne, NE4 5PL, United Kingdom

Location

MeSH Terms

Conditions

Supranuclear Palsy, Progressive; Corticobasal Degeneration; Pick Disease of the Brain

Interventions

Lithium

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Ophthalmoplegia; Ocular Motility Disorders; Cranial Nerve Diseases; Tauopathies; Neurodegenerative Diseases; Paralysis; Neurologic Manifestations; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Frontotemporal Dementia; Frontotemporal Lobar Degeneration; Dementia; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals

Limitations and Caveats

The majority of subjects did not tolerate study drug, therefore, evaluations of subjects on study drug are limited in number.

Results Point of Contact

• Title: René Gonin, PhD (Math. Stats.)
• Organization: Westat

renegonin@westat.com

301-251-1500

Study Officials

• Renè Gonin, PhD

  (Math. Stats.), Westat

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2008
• First Posted: June 23, 2008
• Study Start: September 1, 2008
• Primary Completion: January 1, 2010
• Study Completion: January 1, 2010
• Last Updated: May 17, 2024
• Results First Posted: June 11, 2010

Record last verified: 2024-04

Locations

GB (1); US (8)