ABSTRACT
Huntington's disease (HD) is a neurodegenerative disease for which there is no curative treatment available. Given that the endocannabinoid system is involved in the pathogenesis of HD mouse models, stimulation of specific targets within this signaling system has been investigated as a promising therapeutic agent in HD. We conducted a double-blind, randomized, placebo-controlled, cross-over pilot clinical trial with Sativex(®), a botanical extract with an equimolecular combination of delta-9-tetrahydrocannabinol and cannabidiol. Both Sativex(®) and placebo were dispensed as an oral spray, to be administered up to 12 sprays/day for 12 weeks. The primary objective was safety, assessed by the absence of more severe adverse events (SAE) and no greater deterioration of motor, cognitive, behavioral and functional scales during the phase of active treatment. Secondary objectives were clinical improvement of Unified Huntington Disease Rating Scale scores. Twenty-six patients were randomized and 24 completed the trial. After ruling-out period and sequence effects, safety and tolerability were confirmed. No differences on motor (p = 0.286), cognitive (p = 0.824), behavioral (p = 1.0) and functional (p = 0.581) scores were detected during treatment with Sativex(®) as compared to placebo. No significant molecular effects were detected on the biomarker analysis. Sativex(®) is safe and well tolerated in patients with HD, with no SAE or clinical worsening. No significant symptomatic effects were detected at the prescribed dosage and for a 12-week period. Also, no significant molecular changes were observed on the biomarkers. Future study designs should consider higher doses, longer treatment periods and/or alternative cannabinoid combinations.Clincaltrals.gov identifier: NCT01502046.
Subject(s)
Huntington Disease/drug therapy , Plant Extracts/therapeutic use , Plant Structures , Adult , Amino Acids/pharmacology , Amyloid beta-Peptides/cerebrospinal fluid , Biogenic Monoamines/cerebrospinal fluid , Cannabidiol , Cross-Over Studies , Dronabinol , Drug Combinations , Endocannabinoids/genetics , Endocannabinoids/metabolism , Female , Fibroblasts/drug effects , Follow-Up Studies , Gene Expression Regulation/drug effects , Humans , Huntington Disease/blood , Huntington Disease/cerebrospinal fluid , Male , Mental Status Schedule , MicroRNAs/blood , Middle Aged , Outcome Assessment, Health Care , Peptide Fragments/cerebrospinal fluid , Pilot Projects , Severity of Illness Index , tau Proteins/cerebrospinal fluidABSTRACT
BACKGROUND AND PURPOSE: Therapy for stroke with intravenous tissue plasminogen activator (IV-tPA) is hampered by tight licensing restrictions; some of them have been discussed in recent literature. We assessed the safety and effectiveness of off-label IV-tPA in the clinical settings. METHODS: Retrospective analysis of all the patients treated with IV-tPA at our Stroke Unit. Patients were divided into two groups by licence criteria [on-label group (OnLG), off-label group (OffLG)]. Primary outcome measures were symptomatic intracranial haemorrhages (sICH), major systemic haemorrhages, modified Rankin scale (mRS) and mortality rate at 3months. RESULTS: Five hundred and five patients were registered, 269 (53.2%) were assigned to OnLG and 236 (46.9%) to OffLG. Inclusion criteria for the OffLG were aged >80 years (129 patients), time from onset of symptoms to treatment over 3h (111), prior oral anticoagulant treatment with International Normalised Ratio≤1.7 (41), combination of previous stroke and diabetes mellitus (14), surgery or severe trauma within 3months of stroke (13), National Institutes of Health Stroke Scale score over 25 (11), intracranial tumours (5), systemic diseases with risk of bleeding (7) and seizure at the onset of stroke (2). No significant differences were identified between both groups regarding the proportion of sICH (OnLG 2.2% vs. OffLG 1.6%, P=0.78) or the 3-month mortality rate (11.1% vs. 19%: odds ratio (OR), 1.49; 95% CI, 0.86-2.55; P=0.14). Multivariate analysis showed no significant differences in functional independence at 3months between both groups (mRS <3 64.3% vs. 50.4%: OR mRS >2 1.7; 95% CI, 0.96-2.5; P=0.07). CONCLUSION: Intravenous thrombolysis may be safe and efficacious beyond its current label restrictions.
Subject(s)
Fibrinolytic Agents/administration & dosage , Off-Label Use , Stroke/drug therapy , Thrombolytic Therapy/methods , Tissue Plasminogen Activator/administration & dosage , Aged , Aged, 80 and over , Female , Humans , Infusions, Intravenous , Intracranial Hemorrhages/etiology , Intracranial Hemorrhages/prevention & control , Male , Recovery of Function/drug effects , Retrospective Studies , Stroke/complicationsABSTRACT
OBJECTIVES: To make a retrospective study of the clinical, etiological, diagnostic and prognostic features of cerebral vein and sinus thrombosis (CVST) diagnosed at our University Hospital. METHODS: We performed a systematic research of the clinical records of our University Hospital's electronic database (1977-2009) using the key words <