Cholecalciferol in relapsing-remitting MS: A randomized clinical trial (CHOLINE).

OBJECTIVE: To evaluate the safety and efficacy of cholecalciferol in patients with relapsing-remitting MS (RRMS). METHODS: In this double-blind, placebo-controlled parallel-group, 2-year study, 181 patients with RRMS were randomized 1:1. Key inclusion criteria were a low serum 25-hydroxy vitamin D (25OHD) concentration (<75 nmol/L), a treatment with interferon beta-1a 44 µg (SC 3 times per week) 4 months ± 2 months before randomization, and at least one documented relapse during the previous 2 years. Patients received high-dose oral cholecalciferol 100,000 IU or placebo every other week for 96 weeks. Primary outcome measure was the change in the annualized relapse rate (ARR) at 96 weeks. Secondary objectives included safety and tolerability of cholecalciferol and efficacy assessments (ARR, MRI parameters, and Expanded Disability Status Scale [EDSS]). RESULTS: The primary end point was not met. In patients who completed the 2-year follow-up (45 with cholecalciferol and 45 with placebo), all efficacy parameters favored cholecalciferol with an ARR reduction (p = 0.012), less new hypointense T1-weighted lesions (p = 0.025), a lower volume of hypointense T1-weighted lesions (p = 0.031), and a lower progression of EDSS (p = 0.026). The overall rate of adverse events was well balanced between groups. CONCLUSIONS: Although the primary end point was not met, these data suggest a potential treatment effect of cholecalciferol in patients with RRMS already treated with interferon beta-1a and low serum 25OHD concentration. Together with the good safety profile, these data support the exploration of cholecalciferol treatment in such patients with RRMS. CLINICALTRIALSGOV IDENTIFIER: NCT01198132. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with RRMS and low serum 25OHD, cholecalciferol did not significantly affect ARRs.

Acamprosate for alcohol dependence.

BACKGROUND: Alcohol dependence is among the main leading health risk factors in most developed and developing countries. Therapeutic success of psychosocial programs for relapse prevention is moderate, but could potentially be increased by an adjuvant treatment with the glutamate antagonist acamprosate. OBJECTIVES: To determine the effectiveness and tolerability of acamprosate in comparison to placebo and other pharmacological agents. SEARCH STRATEGY: We searched the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, PubMed, EMBASE and CINAHL in January 2009 and inquired manufacturers and researchers for unpublished trials. SELECTION CRITERIA: All double-blind randomised controlled trials (RCTs) which compare the effects of acamprosate with placebo or active control on drinking-related outcomes. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data. Trial quality was assessed by one author and cross-checked by a second author. Individual patient data (IPD) meta-analyses were used to verify the primary effectiveness outcomes. MAIN RESULTS: 24 RCTs with 6915 participants fulfilled the criteria of inclusion and were included in the review. Compared to placebo, acamprosate was shown to significantly reduce the risk of any drinking RR 0.86 (95% CI 0.81 to 0.91); NNT 9.09 (95% CI 6.66 to 14.28) and to significantly increase the cumulative abstinence duration MD 10.94 (95% CI 5.08 to 16.81), while secondary outcomes (gamma-glutamyltransferase, heavy drinking) did not reach statistical significance. Diarrhea was the only side effect that was more frequently reported under acamprosate than placebo RD 0.11 (95% 0.09 to 0.13); NNTB 9.09 (95% CI 7.69 to 11.11). Effects of industry-sponsored trials RR 0.88 (95% 0.80 to 0.97) did not significantly differ from those of non-profit funded trials RR 0.88 (95% CI 0.81 to 0.96). In addition, the linear regression test did not indicate a significant risk of publication bias (p = 0.861). AUTHORS' CONCLUSIONS: Acamprosate appears to be an effective and safe treatment strategy for supporting continuous abstinence after detoxification in alcohol dependent patients. Even though the sizes of treatment effects appear to be rather moderate in their magnitude, they should be valued against the background of the relapsing nature of alcoholism and the limited therapeutic options currently available for its treatment.

Effects of nicotine and illicit substance use on alcoholism treatment outcomes and acamprosate efficacy.

OBJECTIVES: : To evaluate the effect of current smoking and lifetime illicit drug use on alcoholism treatment outcomes and to assess whether these factors influence acamprosate efficacy. METHODS: : This is a secondary analysis of data from the intention-to-treat population (N = 601) in a 6-month, randomized, placebo-controlled US trial of acamprosate (2 or 3 g/d). Patients met Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria for alcohol dependence and no other dependence disorders other than nicotine or cannabis, although patients with recent substance use were included. Baseline severities of current nicotine dependence and lifetime drug use were determined using the Fagerström test of nicotine dependence and the illicit drug use inventory, respectively. The primary endpoint was rate of good response (abstinence from alcohol for ≥90% of trial). Secondary endpoints were rate of controlled drinking (≤5 drinks/d for ≥90% of trial), percent days abstinent, and percent days controlled drinking. The effect of smoking, drug use, treatment, and any interactions on study endpoints was assessed by a backward selection process to eliminate nonsignificant variables. RESULTS: : In the intention-to-treat population, 44.9% of patients were current smokers and 78.7% reported lifetime illicit drug use. Current nicotine dependence and lifetime illicit drug use were significant negative predictors of rates of good response (nicotine: odds ratio [OR] = 0.56, 95% confidence interval [CI] = 0.35-0.88, P = 0.01; illicit drugs: OR = 0.47, 95% CI = 0.31-0.71, P < 0.01) and all other secondary outcomes. Acamprosate had a significant positive effect on rate of good response (OR = 1.65, 95% CI = 1.08-2.52, P = 0.020) and all other secondary outcomes. CONCLUSIONS: : Current nicotine dependence and lifetime illicit drug use were found to have a significant negative impact on alcoholism treatment outcomes, but no impact on the significant positive effects of acamprosate. The effect sizes of smoking, drug use, and acamprosate are equivalent and thus, treatment with acamprosate may offset some of the negative effects of smoking or drug use on alcoholism treatment outcomes.