Radicava® (Edaravone) Findings in Biomarkers From ALS (REFINE-ALS)
- Conditions
- ALSAmyotrophic Lateral Sclerosis
- Interventions
- Registration Number
- NCT04259255
- Lead Sponsor
- Mitsubishi Tanabe Pharma America Inc.
- Brief Summary
REFINE-ALS is a prospective, observational, longitudinal, multicenter study designed to identify biomarkers to serve as quantifiable biological non-clinical measures of Edaravone effects in ALS. Epigenetic and protein biomarkers will also be investigated.
- Detailed Description
Treatment will be prescribed by HCPs in accordance with their clinical judgement and the prescribing information for Edaravone. The decision to prescribe Edaravone to the participants should be made separately from the decision to enroll then in the study. There will be no randomized assignments to treatment and no restrictions on the use of commercially available medications (but those participating in an experimental study, even if taking Edaravone, will be excluded). No experimental treatment is evaluated in this study. The intervention is limited to the collection of blood and urine samples for biomarker testing.
During the estimated study period, eligible patients who are prescribed Edaravone within the approved indication will be invited to participate in the study. An initial screening/baseline visit will be scheduled for participants who are considered for study participation.
Participants in this study will be followed from enrollment up to 24 weeks after treatment initiation (6 treatment cycles \[each cycle consisting of 28 days\], corresponding to a treatment period of approximately 24 weeks) or premature study discontinuation. Throughout the study period, the investigators will record participant baseline and follow-up information and perform clinical and biomarker assessments.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 300
- Male and female aged 18 years or older at enrollment
- Sporadic or familial ALS diagnosed as possible, probable, probable-laboratory supported or definite as defined by the World Federation of Neurology revised El Escorial criteria
- Decision made to prescribe Edaravone prior to screening
- Participant will likely be able to obtain commercial Edaravone and likely to complete 6 cycles of treatment, per site investigator estimation
- Participant either naïve to Edaravone or who did not receive any Edaravone does within 1 month prior to screening
- Signed informed consent by the subject, or a witness if a subject cannot read or write or is physically unable to talk or write, obtained before any study-related activities are undertaken
- Participant with a contraindication to Edaravone
- Participant is participating in an interventional clinical trial
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Edaravone (Radicava®/Radicava ORS®) Edaravone (Radicava®/Radicava ORS®) During an estimated 12-month period, eligible participants who are prescribed Edaravone within the approved indication will be invited to participate in the study.
- Primary Outcome Measures
Name Time Method Changes in levels of 8-F2 isoprostanes as a potential biomarker of oxidative stress, inflammation or neurodegeneration. Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days). Collection of blood and/or urine samples for 8-F2 isoprostanes.
Change in levels of 3-nitrotyrosine (3-NT) as a potential biomarker of oxidative stress, inflammation or neurodegeneration. Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days). Collection of blood and/or urine samples for 3-NT.
Change in levels of urinary neutrophin receptor p75 as a potential biomarker of oxidative stress, inflammation or neurodegeneration. Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days). Collection of blood and/or urine samples for urinary neutrophin receptor p75.
Change in levels of matrix metalloproteinase-9 (MMP-9) as a potential biomarker of oxidative stress, inflammation or neurodegeneration. Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days). Collection of blood and/or urine samples for MMP-9.
Change in levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a potential biomarker of oxidative stress, inflammation or neurodegeneration. Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days). Collection of blood and/or urine samples 8-OHdG.
Change in levels of urate as a potential biomarker of oxidative stress, inflammation or neurodegeneration. Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days). Collection of blood and/or urine samples for urate.
Change in levels of neurofilaments (Nf) (Heavy and Light) as a potential biomarker of oxidative stress, inflammation or neurodegeneration. Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days). Collection of blood and/or urine samples for neurofilaments (Nf) (Heavy and Light).
Change in levels of creatinine as a potential biomarkers of oxidative stress, inflammation or neurodegeneration. Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days). Collection of blood and/or urine samples for creatinine.
- Secondary Outcome Measures
Name Time Method Change from baseline in slow vital capacity. Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days). The vital capacity (VC) (percent of predicted normal) will be determined, using the upright slow VC method.
Change from baseline in the ALSFRS-R (ALS Functional Rating Scale .Revised) Score Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days). The ALSFRS-R is a quickly administered ordinal rating scale (ratings 0-4) used to determine participants' assessment of their capability and independence in 12 functional activities.
Change from baseline in the King's Clinical Staging. Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days). The King's clinical staging is based on the number of body regions affected by ALS and the presence of respiratory or nutritional failure.
Change from baseline in the ALSAQ-40 (ALS Assessment Questionnaire). Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days). The ALSAQ-40 is a questionnaire that consists of 40 questions/items with 5 discrete scales: physical mobility, activities of daily living and independence, eating and drinking, communication, emotional reactions.
Change from baseline in the Appel ALS Score. Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days). The Appel ALS score consists of five sub-scores: bulbar, respiratory, muscle strength, and lower extremity and upper extremity function.
Change from baseline in hand-held dynamometry. Cycles 1, 3, and 6 of each Edaravone cycle (each cycle is 28 days). Hand-held dynamometry (HHD) will be used as a quantitative measure of muscle strength for this study.
Trial Locations
- Locations (20)
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
SunnyBrook Research Institute
🇨🇦Toronto, Ontario, Canada
Jefferson Weinberg ALS Center
🇺🇸Philadelphia, Pennsylvania, United States
UCLA Als Clinic
🇺🇸Los Angeles, California, United States
Barrow Neurological Institute
🇺🇸Phoenix, Arizona, United States
University of California, San Francisco
🇺🇸San Francisco, California, United States
Las Vegas Clinic
🇺🇸Las Vegas, Nevada, United States
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Colorado
🇺🇸Denver, Colorado, United States
Mercy Health
🇺🇸Grand Rapids, Michigan, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
University of Florida, Jacksonville -Neurology Research Department
🇺🇸Jacksonville, Florida, United States
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States
UC Davis Health
🇺🇸Sacramento, California, United States
University of South Florida
🇺🇸Tampa, Florida, United States
Neurology Associates, P.C.
🇺🇸Lincoln, Nebraska, United States
OhioHealth
🇺🇸Columbus, Ohio, United States
Temple University Lewis Katz School of Medicine
🇺🇸Philadelphia, Pennsylvania, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States