[P02.149] A Pilot Trial of Low Dose Naltrexone in Primary Progressive Multiple Sclerosis

Maira Gironi, Filippo Martinelli, Paola Sacerdote, Claudio Solaro, Genova, Italy, Rosella Cavarretta, Mauro Zaffaroni, Lucia Moiola, Marta Radaelli, Valentina Pilato, Gallarate, Italy, Sebastiano Bucello, Vittorio Martinelli, Marco Cursi, Raffaello Nemni, Giancarlo Comi, Gianvito Martino, Milano, Italy

BACKGROUND: Naltrexone is an orally semi synthetic opiate antagonist licensed, in a 50 mg dose, for the treatment of heroin addiction. However, its opiate antagonist activity is completely abrogated at lower doses while triggering a prolonged up regulation of b -endorphins (BE), an endogenous opioid with immunomodulatory functions. A symptomatic effect on spasticity, pain and fatigue of low dose naltrexone (LDN) in Multiple Sclerosis (MS) has been reported, but only anecdotic observations are available so far. DESIGN/METHODS: A sixth-months, pilot, multicentre, open-label, therapeutic trial with LDN (5 mg/die) has been carried out in 40 patients (pts) with a diagnosis of primary progressive (PP)MS (19 male, mean age 53.4, mean EDSS 5.5). Safety and efficacy of LND on spasticity, pain and fatigue were the major outcome measure of the study. Opioid-containing, immunosuppressive or immunomodulator drugs were considered as a controindication to the study enrolment. Clinical and biochemical evaluations were serially performed (basal, 1- 3-6 months of therapy, 1 month after discontinuation) as well as BE levels (measured by radioimmunoassay) in peripheral blood mononuclear cells (PBMC). Appropriate scales for testing spasticity, pain and fatigue (e.g. Ashworth, Fatigue Severity Scale, Visual Analogue Scale) were used. RESULTS: Thirty-five pts completed the 6 months of therapy (5 drop outs occurred). Transitory haematological abnormalities (increase of liver enzymes), urinary tract infections, mild agitation and sleep disturbance were the commonest adverse events. An increase of PBMC BE levels were measured as soon as 3 months of therapy. BE levels became statistically significant compared to base line values only after 6 month of therapy (p< 0.01). The increase was still statistically significant 1 month after therapy discontinuation (p<0.01 vs basal and 3 month). Efficacy results are under scrutiny. This study has been supported by a grant of Italian Federation of Multiple Sclerosis.
Category - MS and Related Diseases
SubCategory - Clinical Science

Tuesday, April 15, 2008 11:30 AM

Poster Sessions II: Multiple Sclerosis and Related Diseases: Therapeutics (11:30 AM-2:30 PM)

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