ALS
Conditions
Brief summary
The purpose of this research study is to evaluate the safety and effectiveness of Ranolazine, and how well it is tolerated in patients with Amyotrophic Lateral Sclerosis (ALS). Ranolazine is an FDA approved drug that is used for decreasing chest pain.
Detailed description
Amyotrophic Lateral Sclerosis (ALS) is a progressive debilitating and fatal neurodegenerative disease involving the motor neurons in the primary motor cortex, corticospinal tracts, brainstem and spinal cord with 5,000 newly diagnosed patients per year in the USA. There is a pressing need for additional therapies, as the only two FDA-approved drugs for ALS, riluzole and edaravone, showed prolongation of median survival of only two to three months and only a modest benefit in daily functioning, respectively. The ability to identify FDA approved drugs which can be repurposed to ALS, and which may slow disease progression, alleviate symptoms, or prolong survival will have an immediate positive impact of the lives of patients with ALS and their family members. Hypothesis: Ranolazine, an FDA approved drug for angina which inhibits the late Na+ current and intracellular Ca2+ accumulation may be neuroprotective in ALS by reducing neuronal hyperexcitability, may slow disease progression and reduce cramp frequency.
Interventions
Ranolazine is an FDA approved drug for angina (ongoing chest pain or pressure that is felt when the heart does not get enough oxygen).
DRUGRanolazine 1000 MG
Ranolazine is an FDA approved drug for angina (ongoing chest pain or pressure that is felt when the heart does not get enough oxygen).
Sponsors
Gilead Sciences
University of Kansas Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with clinically definite, probable, laboratory supported probable, or possible ALS per revised El Escorial criteria * Cramp frequency greater than 4 cramps per week during 2 week run in * ALS functional rating scale-revised (ALSFRS-R) score of greater than 24 * Able to lie on back for study procedures
Exclusion criteria
* Tracheostomy invasive ventilation, or use of non-invasive ventilation greater than 12 hours per day * Pregnant or lactating * Participation in a prior experimental drug trial less than 30 days prior to screening * Patients taking ranolazine * Patients taking medications which are contraindicated for use with ranolazine such as strong CYP3 inhibitors (ketoconazole, clarithromycin, nelfinavir), and CYP3 inducers (rifampin, phenobarbital) * Patients with clinically significant medical comorbidities (hepatic, renal, cardiac, etc) * Patients with baseline QT interval prolongation on Electrocardiography (ECG) * Patients pre-disposed to secondary QT prolongation for other health conditions like family history of congenital long QT syndrome, heart failure, bradycardia, or cardiomyopathies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicities (DLT) | Up to Week 12 | Measured as any drug-related serious adverse event, or drug-related adverse event necessitating study withdrawal. If a dose has less than 33% DLTs it will be considered tolerable. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Cramp Frequency | Weekly for 12 weeks | The percent change in cramp frequency: average daily cramp frequency, comparing week 12-baseline |
| Percentage Change in Average Weekly Cramp Severity | Weekly for 12 weeks | Percent change in average weekly cramp severity (1 being a very mild muscle cramp and 10 being the most severe cramp you ever experienced) |
| Change in Nocturnal Awakenings Per Week, Comparing Week 12 to Baseline | Weekly for 12 weeks | — |
| Muscle Fasciculations Count | Up to week 12 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ranolazine 500mg Participants will take Ranolazine 500mg twice daily for up to 4 weeks.
Ranolazine 500 MG: Ranolazine is an FDA approved drug for angina (ongoing chest pain or pressure that is felt when the heart does not get enough oxygen). | 6 |
| Ranolazine 1000mg Participants will take Ranolazine 1000mg twice daily for up to 4 weeks.
Ranolazine 1000 MG: Ranolazine is an FDA approved drug for angina (ongoing chest pain or pressure that is felt when the heart does not get enough oxygen). | 8 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 3 |
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Ranolazine 500mg | Ranolazine 1000mg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 6 Participants | 11 Participants |
| Age, Continuous | 53 years | 55 years | 54 years |
| Race/Ethnicity, Customized Caucasian | 6 Participants | 8 Participants | 14 Participants |
| Race/Ethnicity, Customized Non Hispanic | 6 Participants | 8 Participants | 14 Participants |
| Region of Enrollment United States | 6 participants | 8 participants | 14 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 8 |
| other Total, other adverse events | 4 / 6 | 7 / 8 |
| serious Total, serious adverse events | 0 / 6 | 0 / 8 |
Outcome results
Primary
Dose Limiting Toxicities (DLT)
Measured as any drug-related serious adverse event, or drug-related adverse event necessitating study withdrawal. If a dose has less than 33% DLTs it will be considered tolerable.
Time frame: Up to Week 12
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ranolazine 500mg | Dose Limiting Toxicities (DLT) | 1 Participants |
| Ranolazine 1000mg | Dose Limiting Toxicities (DLT) | 2 Participants |
Secondary
Change in Nocturnal Awakenings Per Week, Comparing Week 12 to Baseline
Time frame: Weekly for 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranolazine 500mg | Change in Nocturnal Awakenings Per Week, Comparing Week 12 to Baseline | -1.67 Number of nights awakened | Standard Deviation 2.09 |
| Ranolazine 1000mg | Change in Nocturnal Awakenings Per Week, Comparing Week 12 to Baseline | -4.57 Number of nights awakened | Standard Deviation 6.8 |
Secondary
Muscle Fasciculations Count
Time frame: Up to week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranolazine 500mg | Muscle Fasciculations Count | 33 Muscle fasciculations count | Standard Deviation 25 |
| Ranolazine 1000mg | Muscle Fasciculations Count | 58 Muscle fasciculations count | Standard Deviation 25 |
Secondary
Percentage Change in Average Weekly Cramp Severity
Percent change in average weekly cramp severity (1 being a very mild muscle cramp and 10 being the most severe cramp you ever experienced)
Time frame: Weekly for 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranolazine 500mg | Percentage Change in Average Weekly Cramp Severity | -38.68 Percentage change in average weekly cram | Standard Deviation 19.46 |
| Ranolazine 1000mg | Percentage Change in Average Weekly Cramp Severity | -54.05 Percentage change in average weekly cram | Standard Deviation 39.94 |
Secondary
Percent Change in Cramp Frequency
The percent change in cramp frequency: average daily cramp frequency, comparing week 12-baseline
Time frame: Weekly for 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranolazine 500mg | Percent Change in Cramp Frequency | -39.98 Percent Change in Cramp Frequency | Standard Deviation 23.94 |
| Ranolazine 1000mg | Percent Change in Cramp Frequency | -68.38 Percent Change in Cramp Frequency | Standard Deviation 27.74 |