Hereditary AtaxiaPhase 2NCT00202397
Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
A Phase 2 study testing Riluzole in people with Hereditary Ataxia and Multiple Sclerosis, run by S. Andrea Hospital at 1 site in Italy.
Trial summary
Cerebellar disorders are often disabling and symptomatic therapies are limited to few options that are partially effective. It seems therefore appropriate to search for additional approaches. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hereditary Ataxia, Multiple Sclerosis, Cerebellar Ataxia
- What is being tested?
- Riluzole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteItaly
- Study dates
- Jun 2005to Aug 2008
- Phase
- Phase 2
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with cerebellar degeneration (heredoataxias, sporadic idiopathic ataxia, multiple system atrophy type C)
- Patients who meet McDonald criteria for probable or definite multiple sclerosis (MS) with chronic cerebellar ataxia (not acute cerebellar ataxia due to relapse)
- Age between 18 and 80 years
Who cannot join
- Ataxia due to other diseases
- Acute cerebellar ataxia
- Use of other drugs for chronic ataxia
- Serious concomitant illnesses (cardiac arrhythmias, haematological and hepatic diseases)
- Pregnancy or breast feeding
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 2 Study of Riluzole Effects on Patients With Chronic Cerebellar Ataxia
Cerebellar disorders are often disabling and symptomatic therapies are limited to few options that are partially effective. It seems therefore appropriate to search for additional approaches.
Purkinje cells are the sole output of the cerebellar cortex: they project inhibitory signals to the deep cerebellar nuclei (DCN), which have a critical role in cerebellar function and motor performance. DCN neurons fire spontaneously in the absence of synaptic input from Purkinje neurons and modulation of the DCN response by Purkinje input is believed to be responsible for coordination of movement. Recent evidences support the notion that an increase in DCN excitability may be an important step in the development of cerebellar ataxia and point to the underlying molecular mechanisms: the inhibition of small-conductance calcium-activated potassium (SK) channels, that causes an increase of the firing frequency in DCN, correlates with cerebellar ataxia.
Read more
The rationale of the present project is that SK channel openers, such as riluzole, may have a beneficial effect on cerebellar ataxia.
The researchers propose to perform a pilot study investigating safety and efficacy of riluzole, an approved treatment for amyotrophic lateral sclerosis, as a symptomatic approach in patients with chronic cerebellar ataxia.
Read the detailed description
Forty patients with chronic cerebellar ataxia will be enrolled in a double-bind, randomized, placebo-controlled trial.
By central randomisation, patients will take 50 mg of riluzole or placebo twice daily for 8 weeks.
Electrocardiogram routine laboratory tests and pregnancy tests will be performed before drug administration, after 4 weeks of treatment and at the end of the study (after 8 weeks of treatment).
At the same time points the International Cooperative Ataxia Rating Scale (ICARS) for pharmacological assessment of the cerebellar syndrome will be administered to the two groups (riluzole and placebo) of patients. To guarantee the evaluation of the results in blind conditions, the neurologists who will evaluate the ICARS scores will be different from those who will deal with randomisation and follow-up of patients.
- Conditions
- Hereditary Ataxia, Multiple Sclerosis, Cerebellar Ataxia
- Being tested
- Riluzole, placebo
- Keywords
- cerebellar ataxia, deep cerebellar nuclei (DCN), small-conductance calcium-activated potassium(SK)channels, riluzole, Sporadic ataxia, Multiple system atrophy type C
- Medical subject headings
- Spinocerebellar Degenerations, Multiple Sclerosis, Cerebellar Ataxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RiluzoleDrug
Also called Rilutek ATC Code N07X X02
capsule-shaped 50 mg tablets bid for 8 weeks
placeboOther
capsule-shaped tablet bid for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| 2 | Placebo comparator | placebo bid for 8 weeks Receives: Other: placebo |
| 1 | Experimental | Riluzole, capsule-shaped 50 mg tablets bid for 8 weeks Receives: Drug: Riluzole |
What is being measured
The primary outcome is the main question the study is designed to answer.
The International Cooperative Ataxia Rating Scale (ICARS) total scores and subscores (oculomotor, kinetic, postural, speech), comparing the three time points in the treated versus placebo group
Measured: pre-treatment, after 4 weeks of treatment and at the end of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2005 (estimated)
- Study startJun 2005
- Primary completionJun 2008
- Study completionAug 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Hereditary AtaxiaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- S. Andrea Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Giovanni Ristori, S. Andrea Hospital
- Investigators
- Marco Salvetti, Assoc. Prof, Study director, S.Andrea Hospital, University of Rome "La Sapienza"Giovanni Ristori, MD, Principal investigator, University of Roma La Sapienza
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00202397
- Sponsor's protocol ID
- NEU - RLZ - 05
- Status last verified
- Nov 2024
- First submitted
- 12 Sep 2005
- Last updated
- 2 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Shakkottai VG, Chou CH, Oddo S, Sailer CA, Knaus HG, Gutman GA, Barish ME, LaFerla FM, Chandy KG. Enhanced neuronal excitability in the absence of neurodegeneration induces cerebellar ataxia. J Clin Invest. 2004 Feb;113(4):582-90. doi: 10.1172/JCI20216.
PubMed 14966567Aizenman CD, Huang EJ, Linden DJ. Morphological correlates of intrinsic electrical excitability in neurons of the deep cerebellar nuclei. J Neurophysiol. 2003 Apr;89(4):1738-47. doi: 10.1152/jn.01043.2002.
PubMed 12686564Raman IM, Gustafson AE, Padgett D. Ionic currents and spontaneous firing in neurons isolated from the cerebellar nuclei. J Neurosci. 2000 Dec 15;20(24):9004-16. doi: 10.1523/JNEUROSCI.20-24-09004.2000.
PubMed 11124976Cao YJ, Dreixler JC, Couey JJ, Houamed KM. Modulation of recombinant and native neuronal SK channels by the neuroprotective drug riluzole. Eur J Pharmacol. 2002 Aug 2;449(1-2):47-54. doi: 10.1016/s0014-2999(02)01987-8.
PubMed 12163105Doble A. The pharmacology and mechanism of action of riluzole. Neurology. 1996 Dec;47(6 Suppl 4):S233-41. doi: 10.1212/wnl.47.6_suppl_4.233s.
PubMed 8959995Trouillas P, Takayanagi T, Hallett M, Currier RD, Subramony SH, Wessel K, Bryer A, Diener HC, Massaquoi S, Gomez CM, Coutinho P, Ben Hamida M, Campanella G, Filla A, Schut L, Timann D, Honnorat J, Nighoghossian N, Manyam B. International Cooperative Ataxia Rating Scale for pharmacological assessment of the cerebellar syndrome. The Ataxia Neuropharmacology Committee of the World Federation of Neurology. J Neurol Sci. 1997 Feb 12;145(2):205-11. doi: 10.1016/s0022-510x(96)00231-6.
PubMed 9094050
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study of Riluzole Effects on Patients With Chronic Cerebellar Ataxia
- ClinicalTrials.gov ID
- NCT00202397
- Acronym / sponsor ID
- NEU - RLZ - 05
- Conditions
- Hereditary Ataxia, Multiple Sclerosis, Cerebellar Ataxia
- Keywords
- cerebellar ataxia, deep cerebellar nuclei (DCN), small-conductance calcium-activated potassium(SK)channels, riluzole, Sporadic ataxia, Multiple system atrophy type C
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- S. Andrea HospitalUniversity, hospital or other
- Study start
- Jun 2005
- Primary completion
- Jun 2008 (actual)
- Study completion
- Aug 2008 (actual)
- First posted
- 20 Sep 2005 (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.
Cerebellar disorders are often disabling and symptomatic therapies are limited to few options that are partially effective. It seems therefore appropriate to search for additional approaches.
Purkinje cells are the sole output of the cerebellar cortex: they project inhibitory signals to the deep cerebellar nuclei (DCN), which have a critical role in cerebellar function and motor performance. DCN neurons fire spontaneously in the absence of synaptic input from Purkinje neurons and modulation of the DCN response by Purkinje input is believed to be responsible for coordination of movement. Recent evidences support the notion that an increase in DCN excitability may be an important step in the development of cerebellar ataxia and point to the underlying molecular mechanisms: the inhibition of small-conductance calcium-activated potassium (SK) channels, that causes an increase of the firing frequency in DCN, correlates with cerebellar ataxia.
The rationale of the present project is that SK channel openers, such as riluzole, may have a beneficial effect on cerebellar ataxia.
The researchers propose to perform a pilot study investigating safety and efficacy of riluzole, an approved treatment for amyotrophic lateral sclerosis, as a symptomatic approach in patients with chronic cerebellar ataxia.
Detailed description
Forty patients with chronic cerebellar ataxia will be enrolled in a double-bind, randomized, placebo-controlled trial.
By central randomisation, patients will take 50 mg of riluzole or placebo twice daily for 8 weeks.
Electrocardiogram routine laboratory tests and pregnancy tests will be performed before drug administration, after 4 weeks of treatment and at the end of the study (after 8 weeks of treatment).
At the same time points the International Cooperative Ataxia Rating Scale (ICARS) for pharmacological assessment of the cerebellar syndrome will be administered to the two groups (riluzole and placebo) of patients. To guarantee the evaluation of the results in blind conditions, the neurologists who will evaluate the ICARS scores will be different from those who will deal with randomisation and follow-up of patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 2 | Placebo comparator | Other: placeboplacebo bid for 8 weeks |
| 1 | Experimental | Drug: RiluzoleRiluzole, capsule-shaped 50 mg tablets bid for 8 weeks |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients with cerebellar degeneration (heredoataxias, sporadic idiopathic ataxia, multiple system atrophy type C)
- Patients who meet McDonald criteria for probable or definite multiple sclerosis (MS) with chronic cerebellar ataxia (not acute cerebellar ataxia due to relapse)
- Age between 18 and 80 years
Key exclusion criteria (5 listed)
- Ataxia due to other diseases
- Acute cerebellar ataxia
- Use of other drugs for chronic ataxia
- Serious concomitant illnesses (cardiac arrhythmias, haematological and hepatic diseases)
- Pregnancy or breast feeding
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 |
|---|---|---|
| RiluzoleAlso: Rilutek ATC Code N07X X02capsule-shaped 50 mg tablets bid for 8 weeks | Drug | 1 |
| placebocapsule-shaped tablet bid for 8 weeks | Other | 2 |
Primary outcome
The International Cooperative Ataxia Rating Scale (ICARS) total scores and subscores (oculomotor, kinetic, postural, speech), comparing the three time points in the treated versus placebo group
Time frame: pre-treatment, after 4 weeks of treatment and at the end of the study
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 2 Dec 2024.
- Background: PubMed 14966567Shakkottai VG, Chou CH, Oddo S, Sailer CA, Knaus HG, Gutman GA, Barish ME, LaFerla FM, Chandy KG. Enhanced neuronal excitability in the absence of neurodegeneration induces cerebellar ataxia. J Clin Invest. 2004 Feb;113(4):582-90. doi: 10.1172/JCI20216.
- Background: PubMed 12686564Aizenman CD, Huang EJ, Linden DJ. Morphological correlates of intrinsic electrical excitability in neurons of the deep cerebellar nuclei. J Neurophysiol. 2003 Apr;89(4):1738-47. doi: 10.1152/jn.01043.2002.
- Background: PubMed 11124976Raman IM, Gustafson AE, Padgett D. Ionic currents and spontaneous firing in neurons isolated from the cerebellar nuclei. J Neurosci. 2000 Dec 15;20(24):9004-16. doi: 10.1523/JNEUROSCI.20-24-09004.2000.
- Background: PubMed 12163105Cao YJ, Dreixler JC, Couey JJ, Houamed KM. Modulation of recombinant and native neuronal SK channels by the neuroprotective drug riluzole. Eur J Pharmacol. 2002 Aug 2;449(1-2):47-54. doi: 10.1016/s0014-2999(02)01987-8.
- Background: PubMed 8959995Doble A. The pharmacology and mechanism of action of riluzole. Neurology. 1996 Dec;47(6 Suppl 4):S233-41. doi: 10.1212/wnl.47.6_suppl_4.233s.
- Background: PubMed 9094050Trouillas P, Takayanagi T, Hallett M, Currier RD, Subramony SH, Wessel K, Bryer A, Diener HC, Massaquoi S, Gomez CM, Coutinho P, Ben Hamida M, Campanella G, Filla A, Schut L, Timann D, Honnorat J, Nighoghossian N, Manyam B. International Cooperative Ataxia Rating Scale for pharmacological assessment of the cerebellar syndrome. The Ataxia Neuropharmacology Committee of the World Federation of Neurology. J Neurol Sci. 1997 Feb 12;145(2):205-11. doi: 10.1016/s0022-510x(96)00231-6.
- sponsor siteLink provided by the sponsor.
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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.
Marco Salvetti, Assoc. Prof study director
S.Andrea Hospital, University of Rome "La Sapienza"
Giovanni Ristori, MD principal investigator
University of Roma La Sapienza
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Riluzole in people with Hereditary Ataxia and Multiple Sclerosis, run by S. Andrea Hospital at 1 site in Italy.
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 3 inclusion and 5 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 2 Dec 2024. 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 Italy. 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. Some participants in this study may receive a placebo. 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 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?
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?
The International Cooperative Ataxia Rating Scale (ICARS) total scores and subscores (oculomotor, kinetic, postural, speech), comparing the three time points in the treated versus placebo group (time frame: pre-treatment, after 4 weeks of treatment and at the end of the study). 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 NCT00202397, which also lists 6 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 2 Dec 2024.