Steroid and Behaviour Changes Under Metformin
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Metformin (all participants) Patients with a new indication for Metformin (standard dosage as assigned by the treating physician) therapy. Samples will be collected before and after 12 weeks of Metformin treatment. |
Drug: Metformin
Treatment with Metformin as prescribed by the treating physician.
|
Outcome Measures
Primary Outcome Measures
- Changes in GC-MS measured urinary androgen metabolite levels. [After 12 weeks follow-up]
Changes in urinary androgen metabolite levels of interest (see below) prior to metformin treatment start and after 12-weeks of treatment. Hormones of interest include Androgen-Metabolites (Androsterone, Androstenediol, 11-Oxoetiocholanolone, 11β-Hydroxyandrosterone, 11β-Hydroxyetiocholanolone, Dehydroepiandrosterone, 5-Androstene-3β,17β-diol, 16α-Hydroxydehydroepiandrosterone, 5-Androstene-3β,16α,17β-triol, 5-Pregnene-3β, 16α,17β-triol, Testosterone, 5α-Dihydrotestosterone). All will be measured in urinary samples using GC-MS (gas-chromatography mass-spectrometry).
- Changes in GC-MS measured urinary oestrogen metabolite levels. [After 12 weeks follow-up]
Changes in urinary oestrogen metabolite levels of interest (see below) prior to metformin treatment start and after 12-weeks of treatment. Hormones of interest include Oestrogen-Metabolites (Estriol, 17b-Estradiol), Progesterone-Metabolites (17-Hydroxypregnanolone, Pregnanediol, Pregnanetriol, 11-Oxo-Pregnanetriol). All wil be measured in urinary samples using GC-MS (gas-chromatography mass-spectrometry).
- Changes in GC-MS measured urinary progesterone metabolite levels. [After 12 weeks follow-up]
Changes in urinary progesterone metabolite levels of interest (see below) prior to metformin treatment start and after 12-weeks of treatment. Hormones of interest include Progesterone-Metabolites (17-Hydroxypregnanolone, Pregnanediol, Pregnanetriol, 11-Oxo-Pregnanetriol). All wil be measured in urinary samples using GC-MS (gas-chromatography mass-spectrometry).
- Changes in GC-MS measured urinary aldosterone metabolite levels. [After 12 weeks follow-up]
Changes in urinary aldosterone metabolite levels of interest (see below) prior to metformin treatment start and after 12-weeks of treatment. Hormones of interest include Aldosterone-Metabolites (Tetrahydroaldosterone). All wil be measured in urinary samples using GC-MS (gas-chromatography mass-spectrometry).
- Changes in GC-MS measured urinary corticosterone metabolite levels. [After 12 weeks follow-up]
Changes in urinary corticosterone metabolite levels of interest (see below) prior to metformin treatment start and after 12-weeks of treatment. Hormones of interest include Corticosterone-Metabolites (TetrahydroDOC, Tetrahydrodehydrocorticosterone, Tetrahydrocorticosterone, 5a-Tetrahydrocorticosterone, 18-Hydroxy-tetrahydrocompound A, Cortisone). All wil be measured in urinary samples using GC-MS (gas-chromatography mass-spectrometry).
- Changes in GC-MS measured urinary cortisone metabolite levels. [After 12 weeks follow-up]
Changes in urinary cortisone metabolite levels of interest (see below) prior to metformin treatment start and after 12-weeks of treatment. Hormones of interest include Cortisone-Metabolites (Tetrahydrocortisone, a-Cortolone, b-Cortolone, 20a-Dihydrocortisone, 20b-Dihydrocortisone). All wil be measured in urinary samples using GC-MS (gas-chromatography mass-spectrometry).
- Changes in GC-MS measured urinary cortisol metabolite levels. [After 12 weeks follow-up]
Changes in urinary cortisol metabolite levels of interest (see below) prior to metformin treatment start and after 12-weeks of treatment. Hormones of interest include Cortisol-Metabolites (Cortisol, Tetrahydrocortisol, 5a-Tetrahydrocortisol, a-Cortol, b-Cortol, 20a-Dihydrocortisol, 6b-Hydroxycortisol, 18-Hydroxycortisol). All wil be measured in urinary samples using GC-MS (gas-chromatography mass-spectrometry).
- Behavioral Changes [After 12 weeks follow-up]
Changes in social behavior measured by the Autism-Spectrum Quotient AQ prior to metformin treatment start and after 12-weeks of treatment.
Secondary Outcome Measures
- 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. [After 12 weeks follow-up]
A potential correlation and/or dosage effect between the primary outcomes will be evaluated using the pearson correlation coefficient.
Eligibility Criteria
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:
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Patients under 18 years of age.
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Clinically significant concomitant disease (e.g. advanced renal failure, hepatic dysfunction, neoplasia).
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Significant musculoskeletal disease.
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Active infection during sample collection.
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Immunosuppressive medical therapy.
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Hormonal/steroid treatment.
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Pregnancy.
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Psychiatric disease and known social behavior altering medication (e.g. antipsychotic medication).
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Known or suspected malcompliance, drug or alcohol abuse.
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Inability to follow the procedures of the study, e.g. due to insufficient language skills, severe dementia.
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Life-expectancy < 6 months.
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Poor tolerability to metformin treatment with following treatment discontinuation within duration of follow up.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Lindenhofgruppe | Berne | Switzerland | 3012 |
Sponsors and Collaborators
- University Hospital Inselspital, Berne
- Lindenhofstiftung
Investigators
- Study Director: Markus G Mohaupt, Professor, Lindenhofgruppe Berne and Inselspital Berne, Department of Nephrology
Study Documents (Full-Text)
None provided.More Information
Publications
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- Steroid Changes Metformin