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Steroid and Behaviour Changes Under Metformin

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ClinicalTrials.gov Identifier: NCT04930471
Recruitment Status : Not yet recruiting
First Posted : June 18, 2021
Last Update Posted : June 18, 2021
Sponsor:
Collaborator:
Lindenhofstiftung
Information provided by (Responsible Party):
University Hospital Inselspital, Berne

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
Autistic Disorder Drug: Metformin

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Study Type : Observational
Estimated Enrollment : 45 participants
Observational Model: Cohort
Time Perspective: Prospective
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
Estimated Study Start Date : June 2021
Estimated Primary Completion Date : August 2023
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hormones

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.




Primary Outcome Measures :
  1. 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).


  2. 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).


  3. 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).


  4. 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).


  5. 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).


  6. 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).


  7. 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).


  8. 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.


Secondary Outcome Measures :
  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. [ 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.


Biospecimen Retention:   Samples Without DNA
Urine samples


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients of the the Lindenhofgruppe and its associated practices with a new indication for Metformin treatment.
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04930471


Contacts
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Contact: Benedikt Gasser, MD +41788170711 benedikt.gasser@yahoo.com
Contact: Samuel F Buerki, pract. med. +41797326198 samuel.buerki@bluewin.ch

Locations
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Switzerland
Lindenhofgruppe
Berne, Switzerland, 3012
Contact: Markus G Mohaupt, Professor    +41313663111    markus.mohaupt@lindenhofgruppe.ch   
Sponsors and Collaborators
University Hospital Inselspital, Berne
Lindenhofstiftung
Investigators
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Study Director: Markus G Mohaupt, Professor Lindenhofgruppe Berne and Inselspital Berne, Department of Nephrology
Additional Information:
Publications:

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Responsible Party: University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier: NCT04930471    
Other Study ID Numbers: Steroid Changes Metformin
First Posted: June 18, 2021    Key Record Dates
Last Update Posted: June 18, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by University Hospital Inselspital, Berne:
Steroid hormones
GC-MS
urine analysis
androgens
autism spectrum disorders
Additional relevant MeSH terms:
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Autistic Disorder
Autism Spectrum Disorder
Child Development Disorders, Pervasive
Neurodevelopmental Disorders
Mental Disorders
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs