Clinical trial NCT04930471: Steroid and Behaviour Changes Under Metformin
Official title: A Multi-center, Prospective, Cohort Study to Elucidate the Effects of Metformin Treatment on Steroid Hormones and Social Behavior. Linking Autistic Behaviorial Symptoms to Changes in Steroid Hormone Availability
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Autistic Disorder
Keywords: Steroid hormones
GC-MS
urine analysis
androgens
autism spectrum disorders
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
Collaborators: name: Lindenhofstiftung
First posted: 2021-06-18
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients of the the Lindenhofgruppe and its associated practices with a new indication for Metformin treatment.

Brief summary: Background

Based on various suggestions, social behavior is mediated by a change in steroid hormones. These have diverse effects on the (neuro-)development during critical stages, whereby especially androgen and insulin metabolism seem to play a key role. Various lines of evidence indicate that metformin could influence and improve the symptoms of social withdrawal. Therefore, the investigators will analyze urinary samples of patients before and after treatment with metformin to elucidate the changes in steroid hormone profiles and measure changes in social behavior to examine a potential correlation.

Material \& Methods

Steroid hormone analysis including the most prominent androgen, estrogen, progesterone, aldosterone, corticosterone, cortisone and cortisol metabolites analyzed with gas chromatography mass spectrometry and a questionnaire (Autism-Spectrum Quotient) will be performed prior to and after 12-weeks metformin treatment.

Discussion

It is likely, that due to different pathophysiological mechanisms such as an effect on respiratory chain in mitochondria or via AMP activated protein kinase a general reduction of total androgens will be detected prior versus post metformin treatment. The encompassing measurement of steroid hormones will allow to detect influences on different metabolites and in consequence enzyme activities. The potential changes prior versus post shall give hints concerning the involvement of specific cascades involved, with potential pharmacological targets for future research.


Eligibility criteria: Inclusion Criteria:

* Patients with type 2 diabetes mellitus and an indication for metformin according to the American Diabetes Association (American Diabetes Association, 2021a) starting a new metformin treatment. The main marker will be fasting plasma glucose levels of 7.0mmol/L and/or HbA1c 6.5% (American Diabetes Association, 2021a).
* Written informed consent.

Exclusion Criteria:

* Patients under 18 years of age.
* Clinically significant concomitant disease (e.g. advanced renal failure, hepatic dysfunction, neoplasia).
* Significant musculoskeletal disease.
* Active infection during sample collection.
* Immunosuppressive medical therapy.
* Hormonal/steroid treatment.
* Pregnancy.
* Psychiatric disease and known social behavior altering medication (e.g. antipsychotic medication).
* Known or suspected malcompliance, drug or alcohol abuse.
* Inability to follow the procedures of the study, e.g. due to insufficient language skills, severe dementia.
* Life-expectancy \< 6 months.
* Poor tolerability to metformin treatment with following treatment discontinuation within duration of follow up.

Primary outcomes:
measure: Changes in GC-MS measured urinary androgen metabolite levels.
timeFrame: After 12 weeks follow-up
measure: Changes in GC-MS measured urinary oestrogen metabolite levels.
timeFrame: After 12 weeks follow-up
measure: Changes in GC-MS measured urinary progesterone metabolite levels.
timeFrame: After 12 weeks follow-up
measure: Changes in GC-MS measured urinary aldosterone metabolite levels.
timeFrame: After 12 weeks follow-up
measure: Changes in GC-MS measured urinary corticosterone metabolite levels.
timeFrame: After 12 weeks follow-up
measure: Changes in GC-MS measured urinary cortisone metabolite levels.
timeFrame: After 12 weeks follow-up
measure: Changes in GC-MS measured urinary cortisol metabolite levels.
timeFrame: After 12 weeks follow-up
measure: Behavioral Changes
timeFrame: After 12 weeks follow-up
Secondary outcomes:
measure: Correlation between urinary steroid hormone level changes (metabolites of androgen, oestrogen, progesterone, aldosterone, corticosterone, cortisone and cortisol) and behavioral changes measured with pearson correlation coefficient.
timeFrame: After 12 weeks follow-up
Other outcomes:
Locations:
city: Berne
country: Switzerland
facility: Lindenhofgruppe
Study officials:
affiliation: Lindenhofgruppe Berne and Inselspital Berne, Department of Nephrology
name: Markus G Mohaupt, Professor
role: STUDY_DIRECTOR
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