Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center, 3000 CB, Rotterdam, PO Box 2060, the Netherlands.
Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, the Netherlands.
BMC Psychiatry. 2022 Dec 20;22(1):814. doi: 10.1186/s12888-022-04445-6.
Antipsychotic drugs are an important part of the treatment of irritability and aggression in children with an autism spectrum disorder (ASD). However, significant weight gain and metabolic disturbances are clinically relevant side effects of antipsychotic use in children. In the SPACe study, we showed positive correlations between both risperidone and aripiprazole plasma trough concentrations and weight gain over a 6-month period. The trial SPACe 2: STAR is designed as a follow-up study, in which we aim to research whether therapeutic drug monitoring in clinical practice can prevent severe weight gain, while retaining clinical effectiveness.
SPACe 2: STAR is an international, multicentre, randomised controlled trial (RCT). One hundred forty children aged 6 to 18 who are about to start risperidone or aripiprazole treatment for ASD related behavioural problems will be randomised into one of two groups: a therapeutic drug monitoring (TDM) group, and a care as usual (CAU) group. Participants will be assessed at baseline and 4, 10, 24, and 52 weeks follow-up. In the TDM group, physicians will receive dosing advice based on plasma levels of risperidone and aripiprazole and its metabolites at 4 and 10 weeks. Plasma levels will be measured in dried blood spots (DBS). The primary outcome will be BMI z-score at 24 weeks after start of antipsychotic treatment. Among the secondary outcomes are effectiveness, metabolic laboratory measurements, levels of prolactin, leptin and ghrelin, extrapyramidal side effects, and quality of life.
This will be the first RCT evaluating the effect of TDM of antipsychotic drugs in children and adolescents. Thus, findings from SPACe 2: STAR will be of great value in optimising treatment in this vulnerable population.
ClinicalTrials.gov Identifier: NCT05146245. EudraCT number: 2020-005450-18. Sponsor protocol name: SPACe2STAR. Registered 8 June 2021. Protocol Version 6, Protocol date: 18 august 2022.
抗精神病药物是治疗自闭症谱系障碍（ASD）儿童激惹和攻击行为的重要组成部分。然而，在儿童中使用抗精神病药物会导致显著的体重增加和代谢紊乱等临床相关副作用。在 SPACe 研究中，我们发现利培酮和阿立哌唑的血药谷浓度与 6 个月期间的体重增加呈正相关。试验 SPACe 2：STAR 是一项后续研究，旨在研究在临床实践中进行治疗药物监测是否可以预防严重的体重增加，同时保持临床疗效。
SPACe 2：STAR 是一项国际性、多中心、随机对照试验（RCT）。140 名年龄在 6 至 18 岁之间、即将开始利培酮或阿立哌唑治疗 ASD 相关行为问题的儿童将被随机分为两组：治疗药物监测（TDM）组和常规护理（CAU）组。参与者将在基线和 4、10、24 和 52 周随访时进行评估。在 TDM 组中，医生将根据 4 周和 10 周时利培酮和阿立哌唑及其代谢物的血药浓度提供剂量建议。血药浓度将通过干血斑（DBS）进行测量。主要结局指标是抗精神病治疗开始后 24 周时 BMI z 评分。次要结局指标包括疗效、代谢实验室测量、催乳素、瘦素和胃饥饿素水平、锥体外系副作用和生活质量。
这将是第一项评估儿童和青少年抗精神病药物 TDM 效果的 RCT。因此，SPACe 2：STAR 的研究结果将在优化这一弱势群体的治疗方面具有重要价值。
ClinicalTrials.gov 标识符：NCT05146245。EudraCT 编号：2020-005450-18。赞助商方案名称：SPACe2STAR。2021 年 6 月 8 日注册。方案版本 6，方案日期：2022 年 8 月 18 日。
