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A statistical analysis plan for a randomized clinical trial to evaluate the efficacy and safety of ethosuximide in patients with treatment-resistant depression.
Medicine (Baltimore) 2019; 98(31):e16674M

Abstract

BACKGROUND AND OBJECTIVE

A recent striking advance in the treatment of depression has been the finding of rapid antidepressant effects in over 70% of patients with treatment-resistant depression (TRD) using ketamine. However, the potential risk of addiction may limit its clinical use. Recent research revealed that blockade of N-methyl-D-aspartate receptor (NMDAR) dependent bursting activity in the lateral habenula (LHb) could mediate the fast antidepressant effects of ketamine. Further, LHb bursting plays an important role in the pathophysiology of depression that requires both NMDARs and low-voltage-sensitive T-type calcium channels (T-VSCCs). Ethosuximide, which is used to treat absence seizures, is a T-VSCCs inhibitor, may be a novel drug candidate for depression. The objective of this clinical trial is to investigate the efficacy and safety of ethosuximide in patients with TRD.

DESIGN

The study is a single center, randomized, double-blind, placebo-controlled, parallel-group, two-stage clinical trial. Forty patients with TRD will be randomly assigned to Group A (treatment group) or Group B (control group). In the first stage ethosuximide or placebo will be given for 2 weeks. In the second stage, escitalopram (or another antidepressant if escitalopram has been used before) will be given for the next 4 weeks for all trial patients to ensure effective treatment. The primary outcome measure is the Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Secondary outcome measures include the Quick Inventory of Depressive Symptomatology-Self Report score, Hamilton Anxiety Rating Scale scores, individual scores of MADRS, and Young Mania Rating Scale scores. All these scales are measured at baseline and at each treatment visit. Two-way repeated measures analysis of variance is used to analyze the study outcomes.

DISCUSSION

A statistical analysis plan is employed to enhance the transparency of the clinical trial and reduce the risks of outcome reporting bias and data-driven results.

Authors+Show Affiliations

Department of Psychiatry, the First Affiliated Hospital, College of Medicine, Zhejiang University.Department of Psychiatry, the First Affiliated Hospital, College of Medicine, Zhejiang University. The Key Laboratory of Mental Disorder's Management of Zhejiang Province. Brain Research Institute of Zhejiang University.Center for Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, School of Medicine, Interdisciplinary Institute of Neuroscience and Technology, Qiushi Academy for Advanced Studies.Center for Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, School of Medicine, Interdisciplinary Institute of Neuroscience and Technology, Qiushi Academy for Advanced Studies. Mental Health Center, School of Medicine, Zhejiang University, Hangzhou, China.Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia.Center for Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, School of Medicine, Interdisciplinary Institute of Neuroscience and Technology, Qiushi Academy for Advanced Studies.Department of Psychiatry, the First Affiliated Hospital, College of Medicine, Zhejiang University. The Key Laboratory of Mental Disorder's Management of Zhejiang Province. Brain Research Institute of Zhejiang University.Center for Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, School of Medicine, Interdisciplinary Institute of Neuroscience and Technology, Qiushi Academy for Advanced Studies. Mental Health Center, School of Medicine, Zhejiang University, Hangzhou, China.Department of Psychiatry, the First Affiliated Hospital, College of Medicine, Zhejiang University. The Key Laboratory of Mental Disorder's Management of Zhejiang Province. Brain Research Institute of Zhejiang University.

Pub Type(s)

Clinical Trial Protocol
Journal Article

Language

eng

PubMed ID

31374046

Citation

Jiang, Jiajun, et al. "A Statistical Analysis Plan for a Randomized Clinical Trial to Evaluate the Efficacy and Safety of Ethosuximide in Patients With Treatment-resistant Depression." Medicine, vol. 98, no. 31, 2019, pp. e16674.
Jiang J, Wang Z, Dong Y, et al. A statistical analysis plan for a randomized clinical trial to evaluate the efficacy and safety of ethosuximide in patients with treatment-resistant depression. Medicine (Baltimore). 2019;98(31):e16674.
Jiang, J., Wang, Z., Dong, Y., Yang, Y., Ng, C. H., Ma, S., ... Hu, S. (2019). A statistical analysis plan for a randomized clinical trial to evaluate the efficacy and safety of ethosuximide in patients with treatment-resistant depression. Medicine, 98(31), pp. e16674. doi:10.1097/MD.0000000000016674.
Jiang J, et al. A Statistical Analysis Plan for a Randomized Clinical Trial to Evaluate the Efficacy and Safety of Ethosuximide in Patients With Treatment-resistant Depression. Medicine (Baltimore). 2019;98(31):e16674. PubMed PMID: 31374046.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A statistical analysis plan for a randomized clinical trial to evaluate the efficacy and safety of ethosuximide in patients with treatment-resistant depression. AU - Jiang,Jiajun, AU - Wang,Zheng, AU - Dong,YiYan, AU - Yang,Yan, AU - Ng,Chee H, AU - Ma,Shuangshuang, AU - Xu,Yi, AU - Hu,Hailan, AU - Hu,Shaohua, PY - 2019/8/3/entrez PY - 2019/8/3/pubmed PY - 2019/8/14/medline SP - e16674 EP - e16674 JF - Medicine JO - Medicine (Baltimore) VL - 98 IS - 31 N2 - BACKGROUND AND OBJECTIVE: A recent striking advance in the treatment of depression has been the finding of rapid antidepressant effects in over 70% of patients with treatment-resistant depression (TRD) using ketamine. However, the potential risk of addiction may limit its clinical use. Recent research revealed that blockade of N-methyl-D-aspartate receptor (NMDAR) dependent bursting activity in the lateral habenula (LHb) could mediate the fast antidepressant effects of ketamine. Further, LHb bursting plays an important role in the pathophysiology of depression that requires both NMDARs and low-voltage-sensitive T-type calcium channels (T-VSCCs). Ethosuximide, which is used to treat absence seizures, is a T-VSCCs inhibitor, may be a novel drug candidate for depression. The objective of this clinical trial is to investigate the efficacy and safety of ethosuximide in patients with TRD. DESIGN: The study is a single center, randomized, double-blind, placebo-controlled, parallel-group, two-stage clinical trial. Forty patients with TRD will be randomly assigned to Group A (treatment group) or Group B (control group). In the first stage ethosuximide or placebo will be given for 2 weeks. In the second stage, escitalopram (or another antidepressant if escitalopram has been used before) will be given for the next 4 weeks for all trial patients to ensure effective treatment. The primary outcome measure is the Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Secondary outcome measures include the Quick Inventory of Depressive Symptomatology-Self Report score, Hamilton Anxiety Rating Scale scores, individual scores of MADRS, and Young Mania Rating Scale scores. All these scales are measured at baseline and at each treatment visit. Two-way repeated measures analysis of variance is used to analyze the study outcomes. DISCUSSION: A statistical analysis plan is employed to enhance the transparency of the clinical trial and reduce the risks of outcome reporting bias and data-driven results. SN - 1536-5964 UR - https://www.unboundmedicine.com/medline/citation/31374046/A_statistical_analysis_plan_for_a_randomized_clinical_trial_to_evaluate_the_efficacy_and_safety_of_ethosuximide_in_patients_with_treatment-resistant_depression L2 - http://Insights.ovid.com/pubmed?pmid=31374046 DB - PRIME DP - Unbound Medicine ER -