Effects of Metformin on Androgens and Other Steroid Hormones in Affected Subjects With Autism

NCT ID: NCT06762041

Last Updated: 2025-01-07

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 20 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-01-30
• Study Completion Date: 2026-11-30

Brief Summary

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.

Detailed Description

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.

Conditions

Autism

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Metformin Treatment

Metformin treatment

Intervention Type: DRUG

Interested subjects with autism are treated with metformin with a standard dosage

Interventions

Metformin treatment

Interested subjects with autism are treated with metformin with a standard dosage

Intervention Type: DRUG

Other Intervention Names

Metformin treatment in subjects with autism

Eligibility Criteria

Inclusion Criteria

• Diagnosis with autism according to DSM-V.
• Written informed consent

Exclusion Criteria

• Clinically significant concomitant disease states (e.g. advanced renal failure, hepatic Dysfunction - risk factor of lactate acidosis)
• Significant musculoskeletal disease
• Active infection
• Immunosuppressive medical therapy
• Known or suspected non-compliance, drug or alcohol abuse
• Pregnant or breastfeeding mothers are excluded
• Inability to follow the procedures of the study, e.g. due to insufficient language skills, psychological disorders, very severe dementia inability to report adequately

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Markus Mohaupt, Prof. Dr.

Role: STUDY_DIRECTOR

University of Berne

Central Contacts

Benedikt A Gasser, Dr. Dr,med

Role: CONTACT

benedikt.gasser@yahoo.com

+41 0788170711

References

Gasser BA, Kurz J, Dick B, Mohaupt MG. Steroid Metabolites Support Evidence of Autism as a Spectrum. Behav Sci (Basel). 2019 May 9;9(5):52. doi: 10.3390/bs9050052.

Reference Type: BACKGROUND

PMID: 31075898 (View on PubMed)

Gasser BA, Kurz J, Senn W, Escher G, Mohaupt MG. Stress-induced alterations of social behavior are reversible by antagonism of steroid hormones in C57/BL6 mice. Naunyn Schmiedebergs Arch Pharmacol. 2021 Jan;394(1):127-135. doi: 10.1007/s00210-020-01970-7. Epub 2020 Sep 7.

Reference Type: BACKGROUND

PMID: 32894324 (View on PubMed)

Gasser B, Escher G, Calin AE, Deppeler M, Marchon M, Kurz J, Mohaupt M. Are steroid hormones and autistic traits affected by metformin? First insights from a pilot. Compr Psychoneuroendocrinol. 2023 Jul 29;16:100196. doi: 10.1016/j.cpnec.2023.100196. eCollection 2023 Nov.

Reference Type: BACKGROUND

PMID: 37577184 (View on PubMed)

Gasser B, Escher G, Calin AE, Deppeler M, Marchon M, Mistry HD, Kurz J, Mohaupt MG. Prior to versus after Metformin Treatment-Effects on Steroid Enzymatic Activities. Life (Basel). 2023 Apr 27;13(5):1094. doi: 10.3390/life13051094.

Reference Type: BACKGROUND

PMID: 37240739 (View on PubMed)

Other Identifiers

Lindenhofhospital Berne

Identifier Type: OTHER

Identifier Source: secondary_id

Steroidlabs

Identifier Type: -

Identifier Source: org_study_id