Randomized clinical trial of low dose suramin intravenous infusions for treatment of autism spectrum disorder.

IF 3.6 3区医学 Q1 PSYCHIATRY

Annals of General Psychiatry Pub Date : 2023-11-06 DOI:10.1186/s12991-023-00477-8

David Hough, Alice R Mao, Michael Aman, Reymundo Lozano, Constance Smith-Hicks, Veronica Martinez-Cerdeno, Michael Derby, Zachary Rome, Niel Malan, Robert L Findling

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引用次数: 0

Abstract

Background: There is a critical need for effective treatment of the core symptoms of autism spectrum disorder (ASD). The purinergic antagonist suramin may improve core symptoms through restoration of normal mitochondrial function and reduction of neuro-inflammation via its known antagonism of P2X and P2Y receptors. Nonclinical studies in fragile X knockout mice and the maternal immune activation model support these hypotheses.

Methods: We conducted a 14 week, randomized, double-blind, placebo-controlled proof -of-concept study (N = 52) to test the efficacy and safety of suramin intravenous infusions in boys aged 4-15 years with moderate to severe ASD. The study had 3 treatment arms: 10 mg/kg suramin, 20 mg/kg suramin, and placebo given at baseline, week 4, and week 8. The Aberrant Behavior Checklist of Core Symptoms (ABC-Core) (subscales 2, 3, and 5) was the primary endpoint and the Clinical Global Impressions-Improvement (CGI-I) was a secondary endpoint.

Results: Forty-four subjects completed the study. The 10 mg/kg suramin group showed a greater, but statistically non-significant, numeric improvement (- 12.5 ± 3.18 [mean ± SE]) vs. placebo (- 8.9 ± 2.86) in ABC-Core at Week 14. The 20 mg/kg suramin group did not show improvement over placebo. In exploratory analyses, the 10 mg/kg arm showed greater ABC Core differences from placebo in younger subjects and among those with less severe symptoms. In CGI-I, the 10 mg/kg arm showed a statistically significant improvement from baseline (2.8 ± 0.30 [mean ± SE]) compared to placebo (1.7 ± 0.27) (p = 0.016). The 20 mg/kg arm had a 2.0 ± 0.28 improvement in CGI-I, which was not statistically significant compared to placebo (p = 0.65).

Conclusion: Suramin was generally safe and well tolerated over 14 weeks; most adverse events were mild to moderate in severity. Trial Registration Registered with the South African Health Authority, registration number DOH-27-0419-6116.

Clinicaltrials: Gov registration ID is NCT06058962, last update posted 2023-09-28.

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小剂量苏拉明静脉滴注治疗自闭症谱系障碍的随机临床试验。

背景：迫切需要有效治疗自闭症谱系障碍（ASD）的核心症状。嘌呤能拮抗剂苏拉明可以通过恢复正常线粒体功能和通过已知的P2X和P2Y受体拮抗作用减少神经炎症来改善核心症状。对脆性X基因敲除小鼠和母体免疫激活模型的非临床研究支持这些假设。方法：我们进行了一项为期14周的随机、双盲、安慰剂对照的概念验证研究（N = 52）来测试静脉输注苏拉明对4-15岁患有中度至重度ASD的男孩的疗效和安全性。该研究有3个治疗组：在基线、第4周和第8周给予10 mg/kg苏拉明、20 mg/kg苏拉明和安慰剂。核心症状异常行为检查表（ABC核心）（分量表2、3和5）是主要终点，临床总体印象改善（CGI-I）是次要终点。结果：44名受试者完成了研究。10 mg/kg苏拉明组显示出更大但统计学上无显著的数值改善（-12.5 ± 3.18[平均值 ± SE]）与安慰剂（-8.9 ± 2.86）。20 mg/kg苏拉明组与安慰剂组相比没有改善。在探索性分析中，在年轻受试者和症状较轻的受试者中，10 mg/kg组与安慰剂组的ABC核心差异更大。在CGI-I中，10 mg/kg组与基线相比有统计学意义的改善（2.8 ± 0.30[平均值 ± SE]）与安慰剂（1.7 ± 0.27）（p = 0.016）。20mg/kg组的 ± 0.28 CGI-I改善，与安慰剂相比无统计学意义（p = 0.65）。结论：苏拉明在14周内总体安全且耐受良好；大多数不良事件的严重程度为轻度至中度。在南非卫生局注册的试验注册，注册号DOH-27-0419-6116。临床试验：政府注册ID为NCT06058962，最后更新发布于2023-09-28。

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来源期刊

Annals of General Psychiatry PSYCHIATRY-

CiteScore

6.60

自引率

2.70%

发文量

审稿时长

>12 weeks

期刊介绍： Annals of General Psychiatry considers manuscripts on all aspects of psychiatry, including neuroscience and psychological medicine. Both basic and clinical neuroscience contributions are encouraged. Annals of General Psychiatry emphasizes a biopsychosocial approach to illness and health and strongly supports and follows the principles of evidence-based medicine. As an open access journal, Annals of General Psychiatry facilitates the worldwide distribution of high quality psychiatry and mental health research. The journal considers submissions on a wide range of topics including, but not limited to, psychopharmacology, forensic psychiatry, psychotic disorders, psychiatric genetics, and mood and anxiety disorders.