Phase II trial of the Sigma-1 receptor agonist cutamesine (SA4503) for recovery enhancement after acute ischemic stroke
Language English Country United States Media print-electronic
Document type Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
PubMed
25270629
DOI
10.1161/strokeaha.114.005835
PII: STROKEAHA.114.005835
Knihovny.cz E-resources
- Keywords
- SA 4503, clinical trial, randomized controlled trial, stroke,
- MeSH
- Time Factors MeSH
- Stroke diagnostic imaging physiopathology MeSH
- Adult MeSH
- Double-Blind Method MeSH
- Internationality MeSH
- Brain Ischemia diagnostic imaging physiopathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Recovery of Function physiology MeSH
- Piperazines * pharmacology MeSH
- Radionuclide Imaging MeSH
- Carbon Radioisotopes * pharmacology MeSH
- Sigma-1 Receptor MeSH
- Receptors, sigma agonists MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase II MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Names of Substances
- Piperazines * MeSH
- Carbon Radioisotopes * MeSH
- Receptors, sigma MeSH
- SA 4503 MeSH Browser
BACKGROUND AND PURPOSE: The σ-1 receptor (Sig-1R) agonist cutamesine (SA4503) enhanced functional recovery after experimental stroke with a treatment initiation window of 48 hours and chronic treatment for 28 days. We conducted a phase 2 clinical trial exploring the safety, tolerability, dose range, and functional effects of cutamesine in patients with ischemic stroke. METHODS: Subjects were randomized between 48 and 72 hours after stroke to receive cutamesine 1 mg/d, 3 mg/d, or placebo for 28 days. Effects on safety and function were assessed at baseline, at end of treatment (day 28), and at end of follow-up (day 56). RESULTS: In 60 patients, treatment with both cutamesine dosages was safe and well tolerated without significant differences in numbers of treatment emergent or serious adverse events. No significant effect was observed on the primary efficacy measure (change in National Institutes of Health Stroke Scale from baseline to day 56) or modified Rankin Scale and Barthel Index scores. Post hoc analysis of moderately and severely affected patients (baseline National Institutes of Health Stroke Scale, ≥7 and ≥10) showed greater National Institutes of Health Stroke Scale improvements in the 3 mg/d cutamesine group when compared with placebo (P=0.034 and P=0.038, respectively). A trend toward a higher proportion being able to complete a 10m timed walk was observed for cutamesine-treated subjects. CONCLUSIONS: Cutamesine was safe and well tolerated at both dosage levels. Although no significant effects on functional end points were seen in the population as a whole, greater improvement in National Institutes of Health Stroke Scale scores among patients with greater pretreatment deficits seen in post hoc analysis warrants further investigation. Additional studies should focus on the patient population with moderate-to-severe stroke. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov/show/NCT00639249. Unique identifier: NCT00639249. The EudraCT number is 2007-004840-60 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-004840-60/GB).
References provided by Crossref.org
ClinicalTrials.gov
NCT00639249
