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Pridopidine for the Improvement of Motor Function in Patients With Huntington's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

ABSTRACT: Background: Huntington's disease (HD) is a progressive neurodegenerative disorder. Generally, it is characterized by deficits in cognition, behavior, and movement. Recent studies have shown that pridopidine is a potential and effective drug candidate for the treatment of HD. In the present study, we performed a meta-analysis to evaluate the efficacy and safety of pridopidine in HD. Methods: The MEDLINE, EMBASE, CENTRAL, and Clinicaltrials.gov databases were searched for randomized controlled trials (RCTs) which had that evaluated pridopidine therapy in HD patients. Results: We pooled data from 1,119 patients across four RCTs. Patients in the pridopidine group had a significantly lower Unified Huntington's Disease Rating Scale (UHDRS)-modified Motor Score (mMS) (MD -0.79, 95% CI = -1.46 to -0.11, p = 0.02) than those in the placebo group. Additionally, no differences were observed in the UHDRS-Total Motor Score (TMS) (MD -0.91. 95% CI = -2.03 to 0.21, p = 0.11) or adverse events (RR 1.06, 95% CI = 0.96 to 1.16, p = 0.24) in the pridopidine and placebo groups. In the subgroup analysis, the short-term (≤12 weeks) and long-term (>12 weeks) subgroups exhibited similar efficacy and safety with no statistical significance in TMS, mMS, or adverse events. However, TMS (MD -1.50, 95% CI = -2.87 to -0.12, p = 0.03) and mMS (MD -1.03, 95% CI = -1.87 to -0.19, p = 0.02) were observed to be improved significantly when the dosage of pridopidine ≥90 mg/day. Additionally, pridopidine (≥90 mg/day) increased total adverse events (RR 1.11, 95% CI = 1.00 to 1.22, p = 0.04) compared with placebo. On this basis, we analyzed the incidence of various adverse events when the dosage was ≥90 mg/day. Nonetheless, these results were within the acceptable threshold, although patients developed symptoms, such as nasopharyngitis and insomnia. Conclusion: Pridopidine improved mMS and had no statistical significance in association with TMS or adverse events. Pridopidine (≥90 mg/day) improved TMS and mMS but increased adverse events, such as nasopharyngitis and insomnia. More RCTs were expected to assess pridopidine in HD.

SUBMITTER: Chen S

PROVIDER: S-EPMC8159155 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:In 2012, the United States Food and Drug Administration (FDA) issued a warning regarding potential adverse effects of HMG-CoA reductase inhibitors (statins) on cognition, based on the Adverse Events Reporting System and a review of the medical literature. We aimed to synthesize randomized clinical trial (RCTs) evidence on the association between statin therapy and cognitive outcomes.We searched MEDLINE, EMBASE, and Cochrane CENTRAL through December 2012, and reviewed published systematic reviews of statin treatment. We sought RCTs that compared statin treatment versus placebo or standard care, and reported at least one cognitive outcome (frequency of adverse cognitive events or measurements using standard neuropsychological cognitive test scores). Studies reporting sufficient information to calculate effect sizes were included in meta-analyses. Standardized and unstandardized mean differences were calculated for continuous outcomes for global cognition and for pre-specified cognitive domains. The main outcome was change in cognition measured by neuropsychological tests; an outcome of secondary interest was the frequency of adverse cognitive events observed during follow-up.We identified 25 RCTs (all placebo-controlled) reporting cognitive outcomes in 46,836 subjects, of which 23 RCTs reported cognitive test results in 29,012 participants. Adverse cognitive outcomes attributable to statins were rarely reported in trials involving cognitively normal or impaired subjects. Furthermore, meta-analysis of cognitive test data (14 studies; 27,643 participants) failed to show significant adverse effects of statins on all tests of cognition in either cognitively normal subjects (standardized mean difference 0.01, 95% confidence interval, CI, -0.01 to 0.03, p?=?0.42) or Alzheimer's disease subjects (standardized mean difference -0.05, 95% CI -0.19 to 0.10, p?=?0.38).Statin therapy was not associated with cognitive impairment in RCTs. These results raise questions regarding the continued merit of the FDA warning about potential adverse effects of statins on cognition.

Project description:Background: Bo's abdominal acupuncture (BAA) is a novel therapy in alternative and complementary medicine and has been frequently used for stroke recovery in recent decades. However, no systematic evidence has been performed to confirm the effect and safety of BAA as an adjunctive therapy for post-stroke motor dysfunction (PSMD). Objectives: This review aimed to assess the efficacy and safety of BAA as an adjunctive therapy for improving allover motor function, upper limb motor function, lower limb motor function, and activities of daily living (ADL) in patients with PSMD. Methods: Seven databases were searched from inception to December 2020: Embase, PubMed, Cochrane Library, Chinese Biological Medicine Database, Chinese Scientific Journal Database, WAN FANG, and the China National Knowledge Infrastructure. All randomized controlled trials (RCTs) involving BAA plus another therapy vs. the same other therapy alone were identified. The methodological quality of the included trials was assessed according to the Cochrane risk of bias criteria. If more than half of the domains in a study are at low risk of bias, the overall quality of the study is low risk. We conducted a meta-analysis for primary outcomes using a random effects model and performed a narrative summary for the secondary outcome. We also conducted subgroup analysis for primary outcomes based on different add-on treatments to BAA. Random effects and fixed effects models were used to test the robustness of the pooled data. We also tested the robustness of the meta-analysis using specific methodological variables that could affect primary outcome measures. Results: Twenty-one trials with 1,473 patients were included in this systematic review. The overall quality of the 14 included trials (66.7%) was low risk. Meta-analyses indicated that the effect of the BAA group was better than that of the non-EA group on the Fugl-Meyer Assessment Scale (FMA) (weight mean difference (WMD) 9.53, 95% confidence interval (CI) 7.23 to 11.83, P < 0.00001), FMA for upper extremities (WMD 11.08, 95% CI 5.83 to 16.32, P < 0.0001), FMA for lower extremities (WMD 5.57, 95% CI 2.61 to 8.54, P = 0.0002), and modified Barthel Index (standardized mean difference (SMD) 1.02, 95% CI 0.65 to 1.39, P < 0.00001). Two trials (9.5%) reported BAA-related adverse events, and the most common adverse event was local subcutaneous ecchymosis. Conclusions: BAA as an adjunctive therapy may have clinical benefits for improving allover motor function, upper limb motor function, lower limb motor function, and ADL in patients with PSMD. BAA-related adverse events were rare, tolerable, and recoverable. However, our review findings should be interpreted with caution because of the methodological weaknesses in the included trials. High-quality trials are needed to assess the adjunctive role of BAA in patients with PSMD.

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Pridopidine for the Improvement of Motor Function in Patients With Huntington's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

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