This multicenter, double-blind, clinical study was designed to compare the efficacy and safety of alpha-dihydroergocryptine and flunarizine in the prophylaxis of migraine without aura. One hundred thirty-five patients fulfilling the diagnostic criteria of the International Headache Society were enrolled at five neurologic centers. The study design included a 1-month pretreatment phase with placebo; a 6-month, double-blind, double-dummy treatment phase with alpha-dihydroergocryptine (10 mg twice daily) or flunarizine (5 mg once daily); a further 3-month follow-up phase without treatment. Efficacy was assessed using the patient's diary. Laboratory tests, vital signs, and adverse events were monitored. Analysis of covariance for repeated measures was performed on the intent-to-treat sample. Both treatments led to a significant reduction in the frequency of migraine, days with headache, and use of relief medication. Overall, 51% of those treated with alpha-dihydroergocryptine and 49% of those treated with flunarizine were responders (50% or greater reduction in attack frequency), the average percentage of reduction being 64% with alpha-dihydroergocryptine and 51% with flunarizine. There was no significant difference between the two groups in terms of incidence of adverse events; dizziness and weight gain were the most frequent observed adverse events with alpha-dihydroergocryptine and flunarizine, respectively. Based on the overall improvement in migraine parameters, alpha-dihydroergocryptine can be recommended for use in migraine prophylaxis.

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Introduction/Aims: Becker muscular dystrophy (BMD) is characterized by variable disease severity and progression, prompting the identification of biomarkers for clinical trials. We used data from an ongoing phase II study to provide a comprehensive characterization of a cohort of patients with BMD, and to assess correlations between histological and magnetic resonance imaging (MRI) markers with muscle function and strength. Methods: Eligible patients were ambulatory males with BMD, aged 18 to 65 years (200 to 450 meters on 6-minute walk test). The following data were obtained: function test results, strength, fat-fraction quantification using chemical shift-encoded MRI (whole thigh and quadriceps), and fibrosis and muscle fiber area (MFA) of the brachial biceps. Results: Of 70 patients screened, 51 entered the study. There was substantial heterogeneity between patients in muscle morphology (histology and MRI), with high fat replacement. Total fibrosis correlated significantly and mostly moderately with all functional endpoints, including both upper arm strength assessments (left and right elbow flexion rho À.574 and À.588, respectively [both P < .0001]), as did MRI fat fraction (whole thigh and quadriceps), for example, with four-stair-climb velocity À.554 and À.550, respectively (both P < .0001). Total fibrosis correlated significantly and moderately with both MRI fat fraction assessments (.500 [P = .0003] and .423 [.0024], respectively).

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DF 594, 11-(N-methylnipecotyl)-6, 11-dihydro-5H-pyrido[2,3-b]-l,5-benzodiazepin-5-one hydrochloride, is a new antimuscarinic compound endowed with high affinity for intestinal muscarinic receptors and showing potent inhibitory effects on intestinal motility. This study investigated the intestinal motor effects of DF 594 in fasting, conscious dogs, chronically fitted with electrodes and strain gauges along the small bowel. In a first series of experiments, we assessed the antispasmodic activity of the compound by comparing the ability of intravenous DF 594 or atropine to antagonize the stimulatory effect of bethanechol (100 μg/kg s.c). ED₅₀ values for inhibition of bethanechol-stimulated contractions were 13.9 (8.8–21.8) and 4.0 (1.8–8.7) μg/kg for DF 594 and atropine, respectively. In a second series of experiments, we evaluated the effects of intravenous DF 594 and atropine on the migrating motor complex (MMC), monitoring heart rate as well. Similarly to atropine (30–100 μg/kg), DF 594 (100–300 μg/kg) blocked the further migration of an ongoing MMC and significantly delayed the onset of the following MMC. Unlike atropine, DF 594 had only a minor effect on heart rate at the highest dose tested (300 μg/kg). These data indicate that DF 594 is an effective antispasmodic agent at doses lower than those required to interfere with the MMC and is also less likely than atropine to induce cardiac side effects.

ObjectiveNo treatments are approved for Becker muscular dystrophy (BMD). This study investigated the efficacy and safety of givinostat, a histone deacetylase pan-inhibitor, in adults with BMD.MethodsMales aged 18–65 years with a diagnosis of BMD confirmed by genetic testing were randomized 2:1 to 12 months treatment with givinostat or placebo. The primary objective was to demonstrate statistical superiority of givinostat over placebo for mean change from baseline in total fibrosis after 12 months. Secondary efficacy endpoints included other histological parameters, magnetic resonance imaging and spectroscopy (MRI and MRS) measures, and functional evaluations.ResultsOf 51 patients enrolled, 44 completed treatment. At baseline, there was greater disease involvement in the placebo group than givinostat, based on total fibrosis (mean 30.8 vs. 22.8%) and functional endpoints. Mean total fibrosis did not change from baseline in either group, and the two groups did not differ at Month 12 (least squares mean [LSM] difference 1.04%; p = 0.8282). Secondary histology parameters, MRS, and functional evaluations were consistent with the primary. MRI fat fraction in whole thigh and quadriceps did not change from baseline in the givinostat group, but values increased with placebo, with LSM givinostat–placebo differences at Month 12 of −1.35% (p = 0.0149) and −1.96% (p = 0.0022), respectively. Adverse events, most mild or moderate, were reported by 88.2% and 52.9% patients receiving givinostat and placebo.ConclusionThe study failed to achieve the primary endpoint. However, there was a potential signal from the MRI assessments suggesting givinostat could prevent (or slow down) BMD disease progression.

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