A Multicenter Screening Trial of the Safety and Efficacy of Rasagiline in People with ALS (S36.006)
Notice bibliographique
Résumé
OBJECTIVE: The primary aims are to determine whether rasagiline is safe in this patient population and if the drug has the potential to slow ALS disease progression and to determine if mitochondrial function is affected by rasagiline. BACKGROUND: Oxidative stress, mitochondrial dysfunction and apoptosis have been proposed as the cause of motor neuron death in ALS. Rasagiline, a monoamine oxidase B inhibitor, is FDA-approved for the symptomatic treatment of Parkinson disease. Rasagiline has demonstrated broad neuroprotective activities against a variety of neurotoxins in neuronal cell cultures and in the SOD mouse model of ALS. In vitro experiments indicate rasagiline stabilizes mitochondria under stress conditions. DESIGN/METHODS: Subjects are treated with rasagiline 2 mg daily for 12 months. The primary outcome measures are the number of adverse events and the change of the slope of ALS Functional Rating Scale-Revised (ALSFRS-R) over 12 months. Secondary outcome measures are the change in blood biomarkers including mitochondrial potentials in platelets, leukocytes Bcl/Bax ratio and indicators of apoptosis and oxidative stress following rasagiline administration. RESULTS: Nine centers in the Western ALS (WALS) study group are participating in this study. Total 41 patients screened, 35 were enrolled and 30 remain on treatment with four dropouts due to either side effects (4), and one patient died. There were 18 men and 17 women, with a mean age at entry of 61 years (59-82), and mean disease duration was 1.5 years (0.5-3). 16 patients have been on rasagiline 2 mg for six months. The mean ALSFRS-R for these16 patient were: 37.2 baseline, 36,4 month 1, 32.5 month 6. Mean Jc-1 lymphocyte ratio was 0.46 relative fluorescence at baseline and 0.61 relative fluorescence at six months (P<0.02). CONCLUSIONS: Rasagiline appears to be safe in this ALS population. The change in mitochondrial membrane potentials indicates target engagement of the drug. Supported by: TEVA Pharmaceutical Industries Ltd. Disclosure: Dr. Wang has received research support from Teva Neuroscience. Dr. Moore has nothing to disclose. Dr. Katz has received personal compesnation for actiities with Blue Cross and Talecris. Dr. Katz has received research support from Cytokinetics, Biogen, Neuraltis pharmaceuticals and ALS. Dr. Saperstein has received personal compensation for activities with Talecris, CSL Behring, Eli Lilly,Corinthian reference lab, as speaker, scientific advisory board and neuropathy services. Dr. Walk has nothing to disclose. Dr. Simpson has received personal compensation for activities with Grofels for speaking. Dr. Simpson has received research support from International Foundation Dr. Genge has received personal compensation for activities with Pfizer, Talecris, CSL Behring, Biogen Idec, Novartis, Purdue, and Medtronic. Dr. Bertorini has nothing to disclose. Dr. Fernandes has nothing to disclose. Dr. Swenson has nothing to disclose. Dr. Swerdlow has received personal compensation for activities with Eisai, Inc. as a consultant. Dr. Dimachkie has received personal compensation for activities with Pfizer Inc, Depomed, and Merck & Co., Inc. Dr. McVey has nothing to disclose. Dr. Herbelin has nothing to disclose. Dr. Macchi has nothing to disclose. Dr. Barohn has received personal compensation for activities with Talecris, Genzyme Corporation, and NuFactor. Dr. Barohn has received research support from Alexion Pharmaceuticals. Dr. Herbelin has nothing to disclose.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,002 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,007 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».