title: A pilot trial of low-dose naltrexone in primary progressive multiple sclerosis.
abstract: A sixth month phase II multicenter-pilot trial with a low dose of the opiate antagonist Naltrexone (LDN) has been carried out in 40 patients with primary progressive multiple sclerosis (PPMS). The primary end points were safety and tolerability. Secondary outcomes were efficacy on spasticity, pain, fatigue, depression, and quality of life. Clinical and biochemical evaluations were serially performed. Protein concentration of beta-endorphins (BE) and mRNA levels and allelic variants of the mu-opiod receptor gene (OPRM1) were analyzed. Five dropouts and two major adverse events occurred. The remaining adverse events did not interfere with daily living. Neurological disability progressed in only one patient. A significant reduction of spasticity was measured at the end of the trial. BE concentration increased during the trial, but no association was found between OPRM1 variants and improvement of spasticity. Our data clearly indicate that LDN is safe and well tolerated in patients with PPMS.
authors: Institute of Experimental Neurology (INSPE) and Department of Neurology, San Raffaele Scientific Institute, Via Olgettina 58, Milan, Italy.
authors: M
authors: M
authors: Gironi
authors: F
authors: F
authors: Martinelli-Boneschi
authors: P
authors: P
authors: Sacerdote
authors: C
authors: C
authors: Solaro
authors: M
authors: M
authors: Zaffaroni
authors: R
authors: R
authors: Cavarretta
authors: L
authors: L
authors: Moiola
authors: S
authors: S
authors: Bucello
authors: M
authors: M
authors: Radaelli
authors: V
authors: V
authors: Pilato
authors: Me
authors: M
authors: Rodegher
authors: M
authors: M
authors: Cursi
authors: S
authors: S
authors: Franchi
authors: V
authors: V
authors: Martinelli
authors: R
authors: R
authors: Nemni
authors: G
authors: G
authors: Comi
authors: G
authors: G
authors: Martino
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003863:Depression / Q000453:epidemiology; D006233:Persons with Disabilities; D005221:Fatigue / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D009271:Naltrexone / Q000627:therapeutic use*; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000235:genetics
chemical_list: C485764:OPRM1 protein, human; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu; D009271:Naltrexone