David Hough, Alice R Mao, Michael Aman, Reymundo Lozano, Constance Smith-Hicks, Veronica Martinez-Cerdeno, Michael Derby, Zachary Rome, Niel Malan, Robert L Findling
{"title":"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。","authors":"David Hough, Alice R Mao, Michael Aman, Reymundo Lozano, Constance Smith-Hicks, Veronica Martinez-Cerdeno, Michael Derby, Zachary Rome, Niel Malan, Robert L Findling","doi":"10.1186/s12991-023-00477-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p><p><strong>Clinicaltrials: </strong>Gov registration ID is NCT06058962, last update posted 2023-09-28.</p>","PeriodicalId":7942,"journal":{"name":"Annals of General Psychiatry","volume":null,"pages":null},"PeriodicalIF":3.6000,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10626700/pdf/","citationCount":"0","resultStr":"{\"title\":\"Randomized clinical trial of low dose suramin intravenous infusions for treatment of autism spectrum disorder.\",\"authors\":\"David Hough, Alice R Mao, Michael Aman, Reymundo Lozano, Constance Smith-Hicks, Veronica Martinez-Cerdeno, Michael Derby, Zachary Rome, Niel Malan, Robert L Findling\",\"doi\":\"10.1186/s12991-023-00477-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>Suramin was generally safe and well tolerated over 14 weeks; most adverse events were mild to moderate in severity. 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Randomized clinical trial of low dose suramin intravenous infusions for treatment of autism spectrum disorder.
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.
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.
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