Husain Muhammad Omair, Chaudhry Imran Bashir, Khoso Ameer B, Husain Muhammad Ishrat, Ansari Moin Ahmed, Mehmood Nasir, Naqvi Haider A, Nizami Asad Tamizuddin, Talib Uroosa, Rajput Aatir H, Bassett Paul, Foussias George, Deakin Bill, Husain Nusrat
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Schizophr Bull Open. 2024 Feb 9;5(1):sgae004. doi: 10.1093/schizbullopen/sgae004. eCollection 2024 Jan.
Oxidative stress pathways may play a role in schizophrenia through direct neuropathic actions, microglial activation, inflammation, and by interfering with NMDA neurotransmission. -acetylcysteine (NAC) has been shown to improve negative symptoms of schizophrenia, however, results from trials of other compounds targeting NMDA neurotransmission have been mixed. This may reflect poor target engagement but also that risk mechanisms act in parallel. Sodium Benzoate (NaB) could have an additive with NAC to act on several pathophysiological mechanisms implicated in schizophrenia.
A multicenter, 12 weeks, 2 × 2 factorial design, randomized double-blind placebo-controlled feasibility trial of NaB and NAC added to standard treatment in 68 adults with early schizophrenia. Primary feasibility outcomes included recruitment, retention, and completion of assessments as well as acceptability of the study interventions. Psychosis symptoms, functioning, and cognitive assessments were also assessed.
We recruited our desired sample ( = 68) and retained 78% ( = 53) at 12 weeks, supporting the feasibility of recruitment and retention. There were no difficulties in completing clinical outcome schedules. Medications were well tolerated with no dropouts due to side effects. This study was not powered to detect clinical effect and as expected no main effects were found on the majority of clinical outcomes.
We demonstrated feasibility of conducting a clinical trial of NaB and NAC. Given the preliminary nature of this study, we cannot draw firm conclusions about the clinical efficacy of either agent, and a large-scale trial is needed to examine if significant differences between treatment groups emerge.
ClinicalTrials.gov: NCT03510741.
氧化应激途径可能通过直接的神经病变作用、小胶质细胞激活、炎症以及干扰NMDA神经传递在精神分裂症中发挥作用。N-乙酰半胱氨酸（NAC）已被证明可改善精神分裂症的阴性症状，然而，针对NMDA神经传递的其他化合物试验结果不一。这可能反映出靶点参与度不佳，但也可能是风险机制并行起作用。苯甲酸钠（NaB）可能与NAC具有协同作用，作用于精神分裂症涉及的多种病理生理机制。
一项多中心、为期12周、2×2析因设计、随机双盲安慰剂对照的可行性试验，将NaB和NAC添加到68例早期精神分裂症成年患者的标准治疗中。主要可行性结果包括招募、保留和完成评估以及研究干预措施的可接受性。还评估了精神病症状、功能和认知。
我们招募到了预期样本（n = 68），12周时保留率为78%（n = 53），支持了招募和保留的可行性。完成临床结局时间表没有困难。药物耐受性良好，没有因副作用而退出的情况。本研究没有足够的效力检测临床效果，正如预期的那样，在大多数临床结局上未发现主要效应。
我们证明了进行NaB和NAC临床试验的可行性。鉴于本研究的初步性质，我们无法就任何一种药物的临床疗效得出确凿结论，需要进行大规模试验来检验治疗组之间是否出现显著差异。
ClinicalTrials.gov：NCT03510741。
