Progressive Supranuclear PalsyPhase 1/2NCT00703677
A Pilot Trial of Lithium in Subjects With Progressive Supranuclear Palsy or Corticobasal Degeneration
A Phase 1/2 study testing Lithium in people with Progressive Supranuclear Palsy and Corticobasal Degeneration, run by Westat at 9 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Progressive Supranuclear Palsy, Corticobasal Degeneration
- What is being tested?
- Lithium
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 9 sitesin 2 countries
- Study dates
- Sep 2008to Jan 2010
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
- Creatinine clearance > 50 ml/min
- Able to take oral medication
- 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.)
- Able to identify a study partner
Who cannot join
- 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
Show all 16Show fewer
- 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
- Active psoriasis
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
United States8 sites
University of Maryland
Baltimore, Maryland, 21201
Medical University of South Carolina
Charleston, South Carolina, 29401
Northwestern University
Chicago, Illinois, 60611
Rush University Medical Center
Chicago, Illinois, 60612
University of Louisville
Louisville, Kentucky, 40202
UMDNJ Robert Wood Johnson Medical School
New Brunswick, New Jersey, 08901
Beth Israel Medical Center
New York, New York, 10003
Oregon Health & Science University
Portland, Oregon, 97239-3098
About this study
The goal of this trial is to evaluate the safety and tolerability of lithium in people with progressive supranuclear palsy or corticobasal degeneration.
Read the 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.
- Being tested
- Lithium
- Keywords
- progressive supranuclear palsy, corticobasal degeneration, PSP, CBD, lithium, tau
- Medical subject headings
- Supranuclear Palsy, Progressive, Corticobasal Degeneration, Pick Disease of the Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LithiumDrug
All participants will receive lithium. The dosage will be titrated over a 5-week period and then continued for an additional 6 months.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Lithium |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 28 weeks
Secondary outcomes (9)
Study Drug Compliance
Subjects receiving 80% or more of the prescribed doses between study visits were considered compliant.
Measured: 28 weeks
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.
Measured: 28 weeks
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.
Measured: 28 weeks
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
Measured: 28 weeks
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.
Measured: 28 weeks
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.
Measured: 28 weeks
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.
Measured: 28 weeks
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.
Measured: 28 weeks
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.
Measured: 28 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2008 (estimated)
- Study startSep 2008
- Primary completionJan 2010
- Study completionJan 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Progressive Supranuclear PalsyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Westat
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Renè Gonin, PhD, Principal investigator, (Math. Stats.), Westat
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00703677
- Sponsor's protocol ID
- NPTUNE_PSP_CBD
- Other IDs
- HHSN265200423611C
- Status last verified
- Apr 2024
- First submitted
- 20 Jun 2008
- Last updated
- 17 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Trial of Lithium in Subjects With Progressive Supranuclear Palsy or Corticobasal Degeneration
- ClinicalTrials.gov ID
- NCT00703677
- Acronym / sponsor ID
- NPTUNE_PSP_CBD
- Keywords
- progressive supranuclear palsy, corticobasal degeneration, PSP, CBD, lithium, tau
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- WestatUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Sep 2008
- Primary completion
- Jan 2010 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 23 Jun 2008 (estimated)
- Results
- Posted 11 Jun 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Other | Drug: LithiumAll 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. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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:
- 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.
Key exclusion criteria (16 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LithiumAll participants will receive lithium. The dosage will be titrated over a 5-week period and then continued for an additional 6 months. | Drug | 1 |
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.
9 secondary outcomes
Study Drug Compliance
Time frame: 28 weeks
Changes in Amount of Tau and Phosphorylated Tau in Cerebral Spinal Fluid (CSF)
Time frame: 28 weeks
Change in Brain-Derived Neurotrophic Factor (BDNF) in CSF
Time frame: 28 weeks
Change in Glycogen Synthase Kinase (GSK)-3 Beta Activity
Time frame: 28 weeks
PSP Rating Scale Score: Change From Baseline
Time frame: 28 weeks
Unified Parkinson Disease Rating Scale (UPDRS) Motor Subscale Score: Change From Baseline
Time frame: 28 weeks
PSP-Quality of Life Scale (QoL):Change From Baseline
Time frame: 28 weeks
Frontal Assessment Battery (FAB): Change From Baseline
Time frame: 28 weeks
Geriatric Depression Scale(GDS)-15:Change From Baseline
Time frame: 28 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Renè Gonin, PhD principal investigator
(Math. Stats.), Westat
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Lithium in people with Progressive Supranuclear Palsy and Corticobasal Degeneration, run by Westat at 9 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jun 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ability to Tolerate Lithium Carbonate (time frame: 28 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2024.