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