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临床试验/NCT06762041
NCT06762041尚未招募不适用

A Cohort Study to Elucidate the Effects of Metformin on Androgens and Other Steroid Hormones in Affected Subjects With Autism - a First Pilot Study

Insel Gruppe AG, University Hospital Bern0 个研究点目标入组 20 人开始时间: 2025年1月30日最近更新:
适应症
干预措施
相关药物

试验速览

阶段
不适用
状态
尚未招募
入组人数
20
主要终点
Steroid hormone concentrations of total androgens

研究概览

简要总结

Autism is diagnosed with increasing frequency in recent years despite remaining uncertainty concerning the cause. The disorder is characterized by deficits in social behavior, a lack of communication skills, and repetitive and stereotypical interests. As part of the research, It attempted to pursue the hypothesis that the disorder is signed by an endocrine involvement. Therefore, the original description of Hans Asperger was analyzed first. This was followed by comprehensive steroid hormone analyses in girls and boys with autism. Based on the assumption that steroid hormones are involved, dysregulation of the adrenal gland for all metabolite classes - mineralocorticoid, glucocorticoid, androgen - were identified. The subsequently followed animal experiments yielded to the conclusion that a dysregulation of the hypothalamic-pituitary system might be responsible for the autistic behavior. This is also probably associated with overactivity of 17/20 lyase, an orchestrating enzyme of oxidative stress, which is driven by p38. It is suspected that the increased oxidative stress is of mitochondrial origin and thus other metabolic cascades are involved. Due to the developed understanding of the suspected dysregulation, new therapeutic options for treatment are opening up, with metformin in particular - known for its antiandrogenic effect used in poly cystic ovarian syndrome - appearing to have the best effect on social withdrawal in the developed mouse model. Initial urine analyses allow the assumption that metformin directly influences steroidogenesis, and thus opens up the possibility of a clinical trial for affected subjects with autism.

详细描述

To date, the etiopathogenesis or the biochemical basis of social withdrawal behavior have not been conclusively clarified and accordingly the treatment options are not exhausted. Investigators know from analyzes of those affected by the most severe form of social impairment respectively from subjects with autism that there appears to be a change in the cholesterol-dependent steroid metabolism. Furthermore, it can be assumed that treatment with different substances could be promising. Metformin seems to cause a direct inhibition of the androgen synthesis pathways while parallel influencing social behavior. In principle, Metformin is mainly used to treat Diabetes mellitus type 2. It is a biguanide drug that has been used for more than 60 years. Studies have shown that metformin improves mortality rates in diabetes patients, and younger studies show additional effects in treating cancer, obesity, nonalcoholic fatty liver disease, polycystic ovary syndrome and metabolic syndrome.Treatment with metformin mimics some of the benefits of caloric restriction, such as improved physical performance while yielding to increased insulin sensitivity and reduced low-density lipoprotein and cholesterol levels. Furthermore, as chronic inflammation is also influenced by exercise training it is allowed to assume similar mechanism of Metformin and physical activity. At a molecular level, metformin increases activated protein kinase activity and increases antioxidant protection, resulting in reductions in both oxidative damage accumulation and chronic inflammation thereby mimicking positive effects of endurance training.In consequence, it was indicated that these actions may contribute to the beneficial effects of metformin on health- and lifespan. Focusing on neurologic diseases affected by Metformin positive effects on Alzheimer's disease were shown. Metformin attenuated spatial memory deficit, neuron loss in the hippocampus and enhanced neurogenesis in mice. In another mouse model the metformin treatment counteracted the development of depression-like behaviors in mice suffering social defeat stress when administered. This directly yields to the aim of the study: to assess effects of Metformin on steroid hormones in subjects affected with autism.

研究设计

研究类型
Observational
观察模型
Cohort
时间视角
Prospective

入排标准

年龄范围
18 Years 至 —(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • 未提供

排除标准

  • 未提供

研究组 & 干预措施

Metformin Treatment

干预措施: Metformin treatment (Drug)

结局指标

主要结局

Steroid hormone concentrations of total androgens

时间窗: After 6-9 month of treatment with Metformin

Steroid hormones

次要结局

未报告次要终点

研究者

申办方类型
Other
责任方
Sponsor

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