Steroid and Behaviour Changes Under Metformin

June 10, 2021 updated by: University Hospital Inselspital, Berne

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Anticipated)

45

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

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

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in GC-MS measured urinary androgen metabolite levels.
Time Frame: 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).
After 12 weeks follow-up
Changes in GC-MS measured urinary oestrogen metabolite levels.
Time Frame: 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).
After 12 weeks follow-up
Changes in GC-MS measured urinary progesterone metabolite levels.
Time Frame: 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).
After 12 weeks follow-up
Changes in GC-MS measured urinary aldosterone metabolite levels.
Time Frame: 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).
After 12 weeks follow-up
Changes in GC-MS measured urinary corticosterone metabolite levels.
Time Frame: 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).
After 12 weeks follow-up
Changes in GC-MS measured urinary cortisone metabolite levels.
Time Frame: 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).
After 12 weeks follow-up
Changes in GC-MS measured urinary cortisol metabolite levels.
Time Frame: 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).
After 12 weeks follow-up
Behavioral Changes
Time Frame: 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.
After 12 weeks follow-up

Secondary Outcome Measures

Outcome Measure
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.
Time Frame: After 12 weeks follow-up
A potential correlation and/or dosage effect between the primary outcomes will be evaluated using the pearson correlation coefficient.
After 12 weeks follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Inselspital, Berne

Collaborators

Lindenhofstiftung

Investigators

  • Study Director: Markus G Mohaupt, Professor, Lindenhofgruppe Berne and Inselspital Berne, Department of Nephrology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

June 1, 2021

Primary Completion (Anticipated)

August 1, 2023

Study Completion (Anticipated)

December 1, 2023

Study Registration Dates

First Submitted

June 1, 2021

First Submitted That Met QC Criteria

June 10, 2021

First Posted (Actual)

June 18, 2021

Study Record Updates

Last Update Posted (Actual)

June 18, 2021

Last Update Submitted That Met QC Criteria

June 10, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Steroid Changes Metformin

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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