Lithium Treatment for Patients With Spinocerebellar Ataxia Type I

NCT00683943 | Completed Phase 1

• 2 other identifiers: 08013408-N-0134
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Spinocerebellar Ataxia Type I

Keywords

Spinocerebellar Ataxia; Lithium

Outcome Measures

Primary Outcomes (1)

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

Secondary Outcomes (1)

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

Interventions

Lithium Carbonate DRUG

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Allagui MS, Vincent C, El feki A, Gaubin Y, Croute F. Lithium toxicity and expression of stress-related genes or proteins in A549 cells. Biochim Biophys Acta. 2007 Jul;1773(7):1107-15. doi: 10.1016/j.bbamcr.2007.04.007. Epub 2007 Apr 21.

  PMID: 17512992 BACKGROUND

• Cummings CJ, Sun Y, Opal P, Antalffy B, Mestril R, Orr HT, Dillmann WH, Zoghbi HY. Over-expression of inducible HSP70 chaperone suppresses neuropathology and improves motor function in SCA1 mice. Hum Mol Genet. 2001 Jul 1;10(14):1511-8. doi: 10.1093/hmg/10.14.1511.

  PMID: 11448943 BACKGROUND

• de Chiara C, Menon RP, Dal Piaz F, Calder L, Pastore A. Polyglutamine is not all: the functional role of the AXH domain in the ataxin-1 protein. J Mol Biol. 2005 Dec 9;354(4):883-93. doi: 10.1016/j.jmb.2005.09.083. Epub 2005 Oct 18.

  PMID: 16277991 BACKGROUND

MeSH Terms

Conditions

Spinocerebellar Ataxias

Interventions

Lithium Carbonate

Condition Hierarchy (Ancestors)

Cerebellar Ataxia; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinocerebellar Degenerations; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Ataxia; Dyskinesias; Neurologic Manifestations; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Carbonates; Alkalies; Inorganic Chemicals; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds

Study Officials

• Grisel J Lopez, M.D.

  National Human Genome Research Institute (NHGRI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: May 22, 2008
• First Posted: May 26, 2008
• Study Start: May 18, 2008
• Primary Completion: February 25, 2010
• Study Completion: February 25, 2010
• Last Updated: December 17, 2019

Record last verified: 2014-02-27

Locations

US (1)