Spinocerebellar Ataxia Type IPhase 1NCT00683943
Lithium Treatment for Patients With Spinocerebellar Ataxia Type I
A Phase 1 study testing Lithium Carbonate in people with Spinocerebellar Ataxia Type I, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Spinocerebellar Ataxia Type I
- What is being tested?
- Lithium Carbonate
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 18 May 2008to 25 Feb 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Children
- Pregnant or nursing women
- Anyone on a low-sodium diet
- Cognitively impaired individuals
- Schizophrenics
- Family history of thyroid diseases
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Pilot Study of Tolerability of Lithium Therapy in Patients With Spinocerebellar Ataxia Type I (SCA1)
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.
Read more
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.
Read the 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
- Incidence of side effects
- Side effect profile
Secondary Outcomes
- Timed-up-and-go test
- ICARS score
- SARA score
- Modified Falls Efficacy Scale
- Quantitative Sway/Balance assessment
- Tremor Rating Scale:
- Part A Tremor location/severity rating
- Part B Handwriting and drawings
- Part C Functional disabilities resulting from tremor
- Questionnaires related to sleep, depression (Beck Depression Inventory) (BDI), alertness (Computerized Continuous Performing Tasks) and memory (Mini Mental State Examination)
- Dexterity evaluation At-Home Testing Program device
- Conditions
- Spinocerebellar Ataxia Type I
- Being tested
- Lithium Carbonate
- Keywords
- Spinocerebellar Ataxia, Lithium
- Medical subject headings
- Spinocerebellar Ataxias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lithium CarbonateDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2008 (estimated)
- Study start18 May 2008
- Primary completion25 Feb 2010
- Study completion25 Feb 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Spinocerebellar Ataxia Type IStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- Grisel J Lopez, M.D., Principal investigator, National Human Genome Research Institute (NHGRI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00683943
- Sponsor's protocol ID
- 080134
- Other IDs
- 08-N-0134
- Status last verified
- 27 Feb 2014
- First submitted
- 22 May 2008
- Last updated
- 17 Dec 2019
- Results posted
- No
Publications
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.
PubMed 17512992Cummings 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.
PubMed 11448943de 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.
PubMed 16277991
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Tolerability of Lithium Therapy in Patients With Spinocerebellar Ataxia Type I (SCA1)
- ClinicalTrials.gov ID
- NCT00683943
- Acronym / sponsor ID
- 080134
- Conditions
- Spinocerebellar Ataxia Type I
- Keywords
- Spinocerebellar Ataxia, Lithium
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 18 May 2008
- Primary completion
- 25 Feb 2010 (actual)
- Study completion
- 25 Feb 2010 (actual)
- First posted
- 26 May 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Incidence of side effects
- Side effect profile
Secondary Outcomes
- Timed-up-and-go test
- ICARS score
- SARA score
- Modified Falls Efficacy Scale
- Quantitative Sway/Balance assessment
- Tremor Rating Scale:
- Part A Tremor location/severity rating
- Part B Handwriting and drawings
- Part C Functional disabilities resulting from tremor
- Questionnaires related to sleep, depression (Beck Depression Inventory) (BDI), alertness (Computerized Continuous Performing Tasks) and memory (Mini Mental State Examination)
- Dexterity evaluation At-Home Testing Program device
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (9 listed)
- Children
- Pregnant or nursing women
- Anyone on a low-sodium diet
- Cognitively impaired individuals
- Schizophrenics
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 |
|---|---|---|
| Lithium Carbonate | Drug | – |
Primary outcome
Incidence of side effects, side effect profile, and number of falls.
1 secondary outcome
ICARS scores, SARA scores, Quantitative Sway/Balance assessment, Tremor Rating Scale scores, dexterity evaluation, sleep questionnaire, Computerized Continuous Performing Tasks assessment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Background: PubMed 17512992Allagui 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.
- Background: PubMed 11448943Cummings 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.
- Background: PubMed 16277991de 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.
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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.
Grisel J Lopez, M.D. principal investigator
National Human Genome Research Institute (NHGRI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lithium Carbonate in people with Spinocerebellar Ataxia Type I, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
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 4 inclusion and 9 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 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Incidence of side effects, side effect profile, and number of falls.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00683943, which also lists 3 linked publications.
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 Dec 2019.