Spinocerebellar Ataxias Type 1, Spinocerebellar Ataxias Type 2, Spinocerebellar Ataxias Type 3, Spinocerebellar Ataxias Type 6
Conditions
Brief summary
Investigators expect there will be improvement in walking speed and steadiness after taking Dalfampridine, thereby improving activities of daily living and enhancing social and occupational functions for patients with spinocerebellar ataxia.
Detailed description
Twenty spinocerebellar ataxia patients will be randomized to receive either Dalfampridine or placebo over a total period of 10 weeks. After entering the study, patients will return every 2 weeks for evaluation. After four weeks, intervention will be stopped and patient will enter a 2-week wash out period where they do not take any drug. Then, patients will be given the opposite treatment (Dalfampridine or placebo) and this crossover study will be performed for another 4 weeks. Investigators expect there will be improvement in walking speed and steadiness after taking Dalfampridine, thereby improving activities of daily living and enhancing social and occupational functions.
Interventions
DRUGDalfampridine
Dalfampridine will be provided at an oral dose of 10mg every 12 hours, for 4 weeks period
DRUGPlacebo
Placebo will be administered orally every 12 hours, for a 4 week period.
Sponsors
Acorda Therapeutics
University of Florida
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Individuals at age 18 years or older. * Individuals who can provide the informed consent * Genetic confirmed definite spinocerebellar ataxias (SCA) * Able to complete two trials of the timed 25-foot walk at screening
Exclusion criteria
* Patients who has severe ataxia and unable to ambulate. * Any orthopedic condition that would affect motor performance. * Patients with secondary ataxia from general medical disorders * Individuals who have major psychiatric disorders that prevents compliance * History of epilepsy * Patients with active drug or alcohol use or dependence that would interfere with adherence to study requirements * Inability or unwillingness of subject or legal guardian/representative to give written informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Timed 25 Feet Walking Test (T25FW) | Baseline and 4 weeks after Dalfampridine or placebo | The patient is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The time, in seconds, is calculated from the initiation of the instruction to start and ends when the patient has reached the 25-foot mark. Baseline values are recorded twice. One was at the beginning of the intervention. The second was 2 weeks after washout period and before the second intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Scale of Assessment and Rating of Ataxia (SARA) | Baseline and 4 weeks after Dalfampridine or placebo | Scale for the assessment and rating of ataxia (SARA) is a clinical scale that is based on a semiquantitative assessment of cerebellar ataxia on an impairment level. SARA has 8 items that are related to gait, stance, sitting, speech, finger-chase test, nose-finger test, fast alternating movements and heel-shin test. SARA score ranges from 0 to 40, with higher scores indicating more severe disease. |
| Biomechanical Assessment of Gait (BAG)-Stride Length | Baseline and 4 weeks after Dalfampridine or placebo | Biomechanical Assessment of Gait is a sensitive, quantitative movement analysis system. Stride length was analyzed. Baseline values are recorded twice. One was at the beginning of the intervention. The second was 2 weeks after washout period and before the second intervention. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention ( 4 Weeks) | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 54.9 years STANDARD_DEVIATION 14.3 |
| Region of Enrollment United States | 20 participants |
| SARA at screening visit | 11.1 point STANDARD_DEVIATION 3.4 |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 12 Participants |
| T25FW at screening visit | 25.5 second STANDARD_DEVIATION 9.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 20 | 8 / 19 |
| serious Total, serious adverse events | 0 / 20 | 0 / 19 |
Outcome results
Primary
Change in Timed 25 Feet Walking Test (T25FW)
The patient is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The time, in seconds, is calculated from the initiation of the instruction to start and ends when the patient has reached the 25-foot mark. Baseline values are recorded twice. One was at the beginning of the intervention. The second was 2 weeks after washout period and before the second intervention.
Time frame: Baseline and 4 weeks after Dalfampridine or placebo
Population: Patient with spinocerebellar ataxia (SCA) 1, 2, 3, or 6
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dalfampridine | Change in Timed 25 Feet Walking Test (T25FW) | T25FW at baseline | 23.7 second | Standard Deviation 10.1 |
| Dalfampridine | Change in Timed 25 Feet Walking Test (T25FW) | Change from baseline at 4 weeks | -1.1 second | Standard Deviation 4.7 |
| Placebo | Change in Timed 25 Feet Walking Test (T25FW) | T25FW at baseline | 24.4 second | Standard Deviation 10.1 |
| Placebo | Change in Timed 25 Feet Walking Test (T25FW) | Change from baseline at 4 weeks | -0.3 second | Standard Deviation 4.8 |
Comparison: Null hypothesis is that there was no difference in change of T25FW between Dalfampridine and Placebo. The test was performed with a significant level of 0.05 (two-sided).p-value: >0.05t-test, 2 sided
Secondary
Biomechanical Assessment of Gait (BAG)-Stride Length
Biomechanical Assessment of Gait is a sensitive, quantitative movement analysis system. Stride length was analyzed. Baseline values are recorded twice. One was at the beginning of the intervention. The second was 2 weeks after washout period and before the second intervention.
Time frame: Baseline and 4 weeks after Dalfampridine or placebo
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dalfampridine | Biomechanical Assessment of Gait (BAG)-Stride Length | Sstride Length at baseline | 112.7 cm | Standard Deviation 29.4 |
| Dalfampridine | Biomechanical Assessment of Gait (BAG)-Stride Length | Stride Length at week 4 | 1.6 cm | Standard Deviation 9.4 |
| Placebo | Biomechanical Assessment of Gait (BAG)-Stride Length | Sstride Length at baseline | 111.8 cm | Standard Deviation 30 |
| Placebo | Biomechanical Assessment of Gait (BAG)-Stride Length | Stride Length at week 4 | 4.0 cm | Standard Deviation 9.9 |
Comparison: Null hypothesis is that there was no difference in change of Stride Length on BAG between Dalfampridine and Placebo. The test was performed with a significant level of 0.05 (two-sided).p-value: >0.05t-test, 2 sided
Secondary
Change in Scale of Assessment and Rating of Ataxia (SARA)
Scale for the assessment and rating of ataxia (SARA) is a clinical scale that is based on a semiquantitative assessment of cerebellar ataxia on an impairment level. SARA has 8 items that are related to gait, stance, sitting, speech, finger-chase test, nose-finger test, fast alternating movements and heel-shin test. SARA score ranges from 0 to 40, with higher scores indicating more severe disease.
Time frame: Baseline and 4 weeks after Dalfampridine or placebo
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dalfampridine | Change in Scale of Assessment and Rating of Ataxia (SARA) | SARA at baseline | 10.0 point | Standard Deviation 3.5 |
| Dalfampridine | Change in Scale of Assessment and Rating of Ataxia (SARA) | Change from baseline at week 4 | 0.6 point | Standard Deviation 1.5 |
| Placebo | Change in Scale of Assessment and Rating of Ataxia (SARA) | SARA at baseline | 10.1 point | Standard Deviation 3.3 |
| Placebo | Change in Scale of Assessment and Rating of Ataxia (SARA) | Change from baseline at week 4 | 0.8 point | Standard Deviation 1.8 |
Comparison: Null hypothesis is that there was no difference in change of SARA score between Dalfampridine and Placebo. The test was performed with a significant level of 0.05 (two-sided).p-value: >0.05t-test, 2 sided