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| Name | Class |
|---|---|
| Lindenhofstiftung | UNKNOWN |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin | Drug | Treatment with Metformin as prescribed by the treating physician. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Changes in GC-MS measured urinary androgen metabolite levels. | 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). | After 12 weeks follow-up |
| Changes in GC-MS measured urinary oestrogen metabolite levels. | 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). | After 12 weeks follow-up |
| Changes in GC-MS measured urinary progesterone metabolite levels. | 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). | After 12 weeks follow-up |
| Changes in GC-MS measured urinary aldosterone metabolite levels. | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | A potential correlation and/or dosage effect between the primary outcomes will be evaluated using the pearson correlation coefficient. | After 12 weeks follow-up |
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Inclusion Criteria:
Exclusion Criteria:
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Patients of the the Lindenhofgruppe and its associated practices with a new indication for Metformin treatment.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Benedikt Gasser, MD | Contact | +41788170711 | benedikt.gasser@yahoo.com | |
| Samuel F Buerki, pract. med. | Contact | +41797326198 | samuel.buerki@bluewin.ch |
| Name | Affiliation | Role |
|---|---|---|
| Markus G Mohaupt, Professor | Lindenhofgruppe Berne and Inselspital Berne, Department of Nephrology | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Lindenhofgruppe | Bern | 3012 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 84 | Background | Andonian MR, Barrett AS, Vinogradov SN. Physical properties and subunits of Haemopis grandis erythrocruorin. Biochim Biophys Acta. 1975 Dec 15;412(2):202-13. doi: 10.1016/0005-2795(75)90035-5. | |
| 19047954 | Background | Aufdenblatten M, Baumann M, Raio L, Dick B, Frey BM, Schneider H, Surbek D, Hocher B, Mohaupt MG. Prematurity is related to high placental cortisol in preeclampsia. Pediatr Res. 2009 Feb;65(2):198-202. doi: 10.1203/PDR.0b013e31818d6c24. |
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| ID | Term |
|---|---|
| D001321 | Autistic Disorder |
| D000067877 | Autism Spectrum Disorder |
| ID | Term |
|---|---|
| D002659 | Child Development Disorders, Pervasive |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
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Urine samples
| After 12 weeks follow-up |
| Changes in GC-MS measured urinary corticosterone metabolite levels. | 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). | After 12 weeks follow-up |
| Changes in GC-MS measured urinary cortisone metabolite levels. | 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). | After 12 weeks follow-up |
| Changes in GC-MS measured urinary cortisol metabolite levels. | 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). | After 12 weeks follow-up |
| Behavioral Changes | Changes in social behavior measured by the Autism-Spectrum Quotient AQ prior to metformin treatment start and after 12-weeks of treatment. | After 12 weeks follow-up |
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