Steroid and Behaviour Changes Under Metformin

NCT04930471 | Unknown

• 1 other identifier: Steroid Changes Metformin
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Autistic Disorder

Keywords

Steroid hormones; GC-MS; urine analysis; androgens; autism spectrum disorders

Outcome Measures

Primary Outcomes (8)

• 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).

  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

Secondary Outcomes (1)

• 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

Study Arms (1)

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

Interventions

Metformin DRUG

Treatment with Metformin as prescribed by the treating physician.

Metformin (all participants)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients of the the Lindenhofgruppe and its associated practices with a new indication for Metformin treatment.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• Lindenhofstiftung: collaborator

Study Sites (1)

Lindenhofgruppe

Bern, 3012, Switzerland

Location

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Biospecimen

Retention: SAMPLES WITHOUT DNA

Urine samples

MeSH Terms

Conditions

Autistic Disorder; Autism Spectrum Disorder

Interventions

Metformin

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Markus G Mohaupt, Professor

  Lindenhofgruppe Berne and Inselspital Berne, Department of Nephrology

  STUDY DIRECTOR

Central Study Contacts

Benedikt Gasser, MD

CONTACT

+41788170711; benedikt.gasser@yahoo.com

Samuel F Buerki, pract. med.

CONTACT

+41797326198; samuel.buerki@bluewin.ch

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2021
• First Posted: June 18, 2021
• Study Start: June 1, 2021
• Primary Completion: August 1, 2023
• Study Completion: December 1, 2023
• Last Updated: June 18, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)