Lithium Treatment for Patients With Spinocerebellar Ataxia Type I

Brief Title

Lithium Treatment for Patients With Spinocerebellar Ataxia Type I

Official Title

Pilot Study of Tolerability of Lithium Therapy in Patients With Spinocerebellar Ataxia Type I (SCA1)

Brief Summary

      This study will evaluate the side effects and tolerability of the drug lithium in patients
      with spinocerebellar ataxia type I (SCA1) an inherited disorder caused by loss of nerve cells
      in parts of the brain. Symptoms include ataxia (difficulty walking) and loss of muscle
      coordination and strength. Recent studies suggest that lithium may be helpful in treating
      some SCA1 symptoms.

      People between 18 and 65 years of age with SCA1 who have only difficulty walking or who have
      difficulty walking as well as tremor, hand incoordination or speech problems, may be eligible
      for this study. Participation requires three hospital admissions at the NIH Clinical Center
      and one outpatient visit.

      Participants undergo the following tests and procedures:

      Admission 1 (2-6 weeks)

        -  Medical history, physical examination, blood and urine tests, electrocardiogram.

        -  Evaluation of SCA1 symptoms (balance, walking, dexterity, tremor, memory, mood and
           concentration).

        -  Monitoring of liquid intake and output (urine) and weight changes.

        -  Lithium treatment Start treatment and remain in hospital until the blood level of the
           drug is stabilized; continue treatment at home after hospital discharge.

      Admission 2 (2-4 days, 4 weeks after hospital discharge).

        -  Repeat of some or all of the procedures done at the first admission.

        -  Continue lithium in hospital and at home after discharge, with local physician checking
           laboratory values as needed.

      Admission 3 (2-4 days, 8 weeks after Admission 2).

        -  Repeat of some or all of the procedures done at other admissions.

        -  Stop lithium.

      Outpatient Visit (4 weeks after Admission 3)

        -  Evaluation of SCA1 symptoms.

        -  Blood and urine tests.
    

Detailed Description

      Objective

      Evaluation of tolerability and safety of lithium in SCA1 patients.

      Study Population

      A total of 10 molecularly diagnosed SCA1 patients divided in two groups. One group would be
      composed of 5 patients with gait difficulty only and 5 patients with gait difficulty and
      tremor, hand incoordination or speech difficulties.

      Design

      Patients will be admitted to the NIH Clinical Center for initiation and titration of Lithium
      until high therapeutic levels currently accepted for the treatment of Bipolar affective
      disorder are achieved (1.0-1.2 mmol/L) or a maximum tolerated dose. During their admissions,
      they will have neurological evaluations, ataxia and tremor evaluations, timed-up-and-go
      testing, quality of life assessment, questionnaires evaluating sleep, balance confidence and
      depression, memory testing, alertness assessment and quantitative balance/sway evaluations.
      Parameters and side effect profiles will be assessed at baseline, 1 month (plus or minus 5
      days) and 3 months (plus or minus 5 days) after achievement of therapeutic levels. They will
      also have an exit evaluation one month (plus or minus 5 days) after discontinuation of
      Lithium also at the NIH. For their baseline evaluation and titration, patients will be
      admitted to the NIH for 4 weeks plus or minus 2 weeks. Evaluation at 1 month (plus or minus 5
      days) and 3 months (plus or minus 5 days)

      Outcome Measures

      Primary Outcomes

        1. Incidence of side effects

        2. Side effect profile

      Secondary Outcomes

        1. Timed-up-and-go test

        2. ICARS score

        3. SARA score

        4. Modified Falls Efficacy Scale

        5. Quantitative Sway/Balance assessment

        6. Tremor Rating Scale:

             -  Part A Tremor location/severity rating

             -  Part B Handwriting and drawings

             -  Part C Functional disabilities resulting from tremor

        7. Questionnaires related to sleep, depression (Beck Depression Inventory) (BDI), alertness
           (Computerized Continuous Performing Tasks) and memory (Mini Mental State Examination)

        8. Dexterity evaluation At-Home Testing Program device
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Incidence of side effects, side effect profile, and number of falls.

Secondary Outcome

 ICARS scores, SARA scores, Quantitative Sway/Balance assessment, Tremor Rating Scale scores, dexterity evaluation, sleep questionnaire, Computerized Continuous Performing Tasks assessment

Condition

Spinocerebellar Ataxia Type I

Intervention

Lithium Carbonate


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

13

Start Date

May 18, 2008

Completion Date

February 25, 2010

Primary Completion Date

February 25, 2010

Eligibility Criteria

        -  INCLUSION CRITERIA:

          -  18-65 years of age

          -  Molecularly diagnosed SCA1

          -  Gait disturbance only or gait disturbance and tremor and/or hand incoordination and/or
             speech difficulty.

          -  Women of childbearing age who agree to use contraceptive methods for the duration of
             the study.

        EXCLUSION CRITERIA:

          -  Children

          -  Pregnant or nursing women

          -  Anyone on a low-sodium diet

          -  Cognitively impaired individuals

          -  Schizophrenics

          -  Family history of thyroid diseases

          -  Patients with medical conditions that can be affected by Lithium such as diabetes
             mellitus, difficulty urinating, infections (severe occurring with fever, prolonged
             sweating, diarrhea, or vomiting), kidney disease, epilepsy, thyroid disease, heart
             disease, pulmonary disease, bipolar affective disorder, cardiac arrhythmia, diabetes
             insipidus, Parkinson disease, psoriasis and leukemia.

          -  Anyone taking the following medications: diuretics, nonsteroidal anti-inflammatory
             agents, methyldopa, tetracycline, antipsychotic, neuromuscular blocking agents,
             digoxin, phenytoin, acetazolamide, calcium iodide, iodinated glycerol, potassium
             iodide, calcium channel blockers and/or metronidazole. Patients on these medications
             may be enrolled and their lithium levels will be followed very closely. If levels are
             consistently maintained, the subject may remain in the study.

          -  Age greater than 65 years
      

Gender

All

Ages

18 Years - 65 Years

Accepts Healthy Volunteers

No

Contacts

Grisel J Lopez, M.D., , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00683943

Organization ID

080134

Secondary IDs

08-N-0134


Study Sponsor

National Institute of Neurological Disorders and Stroke (NINDS)


Study Sponsor

Grisel J Lopez, M.D., Principal Investigator, National Human Genome Research Institute (NHGRI)


Verification Date

February 27, 2014