Ellegaard Pernille Kempel, Licht Rasmus Wentzer, Poulsen Henrik Enghusen, Nielsen René Ernst, Berk Michael, Dean Olivia May, Mohebbi Mohammadreza, Nielsen Connie Thuroee
Institute of Regional Health Services Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
Research Unit, Mental Health Service Esbjerg, Gl. Vardevej 101, 6715, Esbjerg N, The Region of Southern Denmark, Denmark.
Int J Bipolar Disord. 2018 Apr 5;6(1):11. doi: 10.1186/s40345-018-0117-9.
Oxidative stress and inflammation may be involved in the development and progression of mood disorders, including bipolar disorder. Currently, there is a scarcity of useful treatment options for bipolar depressive episodes, especially compared with the efficacy of treatment for acute mania. N-Acetylcysteine (NAC) has been explored for psychiatric disorders for some time given its antioxidant and anti-inflammatory properties. The current trial aims at testing the clinical effects of adjunctive NAC treatment (compared to placebo) for bipolar depression. We will also explore the biological effects of NAC in this context. We hypothesize that adjunctive NAC treatment will reduce symptoms of depression, which will be reflected by changes in selected markers of oxidative stress.
In the study, we will include adults diagnosed with bipolar disorder, in a currently depressive episode. Participants will undertake a 20-week, adjunctive, randomized, double-blinded, parallel group placebo-controlled trial comparing 3 grams of adjunctive NAC daily with placebo. The primary outcome is the mean change over time from baseline to end of study on the Montgomery-Asberg Depression Rating Scale (MADRS). Among the secondary outcomes are mean changes from baseline to end of study on the Bech-Rafaelsen Melancholia Scale (MES), the Young Mania Rating Scale (YMRS), the WHO-Five Well-being Index (WHO-5), the Global Assessment of Functioning scale (GAF-F), the Global Assessment of Symptoms scale (GAF-S) and the Clinical Global Impression-Severity scale (CGI-S). The potential effects on oxidative stress by NAC treatment will be measured through urine and blood samples. DNA will be examined for potential polymorphisms related to oxidative defences.
Registered at The European Clinical Trials Database, ClinicalTrials.gov: NCT02294591 and The Danish Data Protection Agency: 2008-58-0035.
氧化应激和炎症可能参与包括双相情感障碍在内的情绪障碍的发生和发展。目前，双相抑郁发作的有效治疗选择匮乏，尤其是与急性躁狂的治疗效果相比。鉴于N-乙酰半胱氨酸（NAC）具有抗氧化和抗炎特性，其已被研究用于精神疾病一段时间。当前试验旨在测试辅助使用NAC治疗（与安慰剂相比）对双相抑郁的临床效果。我们还将在此背景下探究NAC的生物学效应。我们假设辅助使用NAC治疗将减轻抑郁症状，这将通过氧化应激选定标志物的变化得以体现。
在本研究中，我们将纳入目前处于抑郁发作期的双相情感障碍成年患者。参与者将进行一项为期20周的辅助性、随机、双盲、平行组安慰剂对照试验，比较每日3克辅助性NAC与安慰剂的效果。主要结局是从基线到研究结束时蒙哥马利-阿斯伯格抑郁评定量表（MADRS）随时间的平均变化。次要结局包括从基线到研究结束时贝克-拉范森抑郁量表（MES）、杨氏躁狂评定量表（YMRS）、世界卫生组织五福指数（WHO-5）、功能总体评定量表（GAF-F）、症状总体评定量表（GAF-S）和临床总体印象-严重程度量表（CGI-S）的平均变化。NAC治疗对氧化应激的潜在影响将通过尿液和血液样本进行测量。将检测DNA中与氧化防御相关的潜在多态性。
已在欧洲临床试验数据库、ClinicalTrials.gov注册：NCT02294591以及丹麦数据保护局注册：2008-58-0035。
