Exploring the Relationship Between Androgen Metabolism, Metabolic Disease and Skeletal Muscle Energy Balance in Men

NCT05773183 | Unknown

• 1 other identifier: MMetDMH
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This study relates to men with hypogonadism, a condition describing a deficiency of androgens such as testosterone. Deficiency of these hormones occurs in men due to testicular (primary) or hypothalamic-pituitary (secondary) problems or may be observed in men undergoing androgen deprivation therapy for prostate cancer. Testosterone plays an important role in male sexual development and health, but also plays a key role in metabolism and energy balance. Men with testosterone deficiency have higher rates of metabolic dysfunction. This results in conditions such as obesity, nonalcoholic fatty liver disease, diabetes, and cardiovascular disease. Studies have confirmed that treating testosterone deficiency with testosterone can reduce the risk of some of these adverse metabolic outcomes, however cardiovascular mortality remains higher than the general population. We know that testosterone deficiency therefore causes metabolic dysfunction. However, research to date has not established the precise mechanisms behind this. In men with hypogonadism there is a loss of skeletal muscle bulk and function. Skeletal muscle is the site of many critical metabolic pathways; therefore it is likely that testosterone deficiency particularly impacts metabolic function at this site. Men with testosterone deficiency also have excess fat tissue, this can result in increased conversion of circulating hormones to a type of hormone which further suppresses production of testosterone. The mechanism of metabolic dysfunction in men with hypogonadism is therefore multifactorial. The purpose of this study is to dissect the complex mechanisms linking obesity, androgens and metabolic function in men. Firstly, we will carry out a series of detailed metabolic studies in men with testosterone deficiency, compared to healthy age- and BMI-matched men. Secondly, we will perform repeat metabolic assessment of hypogonadal men 6 months after replacement of testosterone in order to understand the impact of androgen replacement on metabolism. Lastly, we will perform the same detailed metabolic assessment in men with prostate cancer before and after introduction of a drug which causes testosterone deficiency for therapeutic purposes.

Conditions

Hypogonadism, Male; Testosterone Deficiency; Prostate Cancer; Androgen Deficiency; Metabolic Disease; Metabolic Syndrome; Metabolic Disturbance; Obesity; Cardiovascular Diseases; NAFLD; Diabetes

Keywords

mechanism; mechanistic study

Outcome Measures

Primary Outcomes (3)

• To compare differences in non-targeted serum and skeletal muscle metabolomics in men with hypogonadism compared to controls

  Differences in non-targeted serum and skeletal muscle metabolomics in men with hypogonadism compared to controls

  24 months

• To compare differences in non-targeted serum and skeletal muscle metabolomics in men with hypogonadism pre and post testosterone replacement

  Differences in non-targeted serum and skeletal muscle metabolomics in men

  24 months

• To compare differences in steroid metabolomics in men with prostate cancer pre- and post-androgen deprivation therapy (ADT)

  Differences in steroid metabolomics in men with prostate cancer pre- and post-androgen deprivation therapy (ADT)

  24 months

Secondary Outcomes (4)

• To compare differences in steroid metabolomics in men with hypogonadism compared to controls

  24 months

• To compare differences in steroid metabolomics in men with hypogonadism pre and post testosterone replacement

  24 months

• To compare differences in steroid metabolomics in men with prostate cancer pre- and post-androgen deprivation therapy

  24 months

• To compare differences in metabolic phenotype in (i) hypogonadal men compared to healthy men (ii) hypogonadal men pre and post testosterone replacement therapy (iii) men with prostate cancer post initiation of Androgen Deprivation Therapy

  24 months

Study Arms (3)

OBS1 [Observational Cohort 1]

20 Eugonadal Healthy men 20 Men with Testosterone Deficiency not currently on Testosterone replacement therapy

IC1 [Interventional Cohort 1]

20 Men with Testosterone Deficiency progressed from OBS1 6 months post initiation of testosterone replacement therapy

Drug: Testosterone

IC2 [Interventional Cohort 2]

20 men with prostate cancer planned for GnRH analogue therapy

Drug: GnRH

Interventions

Testosterone DRUG

In OBS1 20 men will be started on Testosterone replacement therapy as per routine clinical practice. Data collection will occur prior initiating therapy, and 6 months post

IC1 [Interventional Cohort 1]

GnRH DRUG

20 men in OBS2 planned for GnRH analogue therapy will undergo data collection prior, and 3 months post initiation of GnRH analogue therapy

Also known as: GnRH analogue

IC2 [Interventional Cohort 2]

Eligibility Criteria

• Age: 18 Years - 60 Years
• Gender Eligibility Details: Male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Observational Cohort 1 (OBS1): * 20 eugonadal healthy volunteer controls * 20 hypogonadal men pre initiation of testosterone replacement therapy Interventional Cohort 1 (IC1): • 20 hypogonadal men 6 months post initiation of testosterone replacement therapy Interventional Cohort 2 (IC2): • 20 men with prostate cancer pre and 3 months post initiation of GnRH analogue therapy

You may qualify if:

• Able to provide consent
• Ages 18 - 60 years
• BMI 20 - 35 kg / m2
• Able to provide consent
• Ages 40-85 years
• BMI 20 - 35 kg / m2

You may not qualify if:

• Contraindication to testosterone replacement for patients with hypogonadism
• BMI \<20 or \> 35 kg / m2
• Age \< 18 or \> 60 years
• Diabetes Mellitus
• Confirmed ischaemic heart disease
• In patients with secondary hypogonadism co-existence of any untreated pituitary hormone deficiencies (ACTH, TSH, GH deficiency)
• Glucocorticoid use via any route within the last three months
• Current intake of drugs known to impact upon steroid or metabolic function or intake of such drugs during the six months preceding the planned recruitment
• Diabetes mellitus
• Confirmed ischaemic heart disease
• Any glucocorticoid therapy in the last 3 months (inhaled/transdermal/systemic)
• BMI \<20 or \>35
• Pre-existing hormonal pathology - primary testicular or pituitary pathology
• Age \<40 or \>85

Sponsors & Collaborators

• Royal College of Surgeons, Ireland: lead
• Steroid Metabolism Analysis Core, University of Birmingham: collaborator
• University of Liverpool: collaborator

Study Sites (1)

Beaumont Hospital

Dublin, Ireland

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum Samples for targeted and non targeted metabolomics Saliva samples for targeted metabolomics Urine samples for targeted metabolomics Skeletal muscle samples for non targeted metabolomics

MeSH Terms

Conditions

Eunuchism; Prostatic Neoplasms; Metabolic Diseases; Metabolic Syndrome; Obesity; Cardiovascular Diseases; Non-alcoholic Fatty Liver Disease; Diabetes Mellitus

Interventions

Testosterone; Gonadotropin-Releasing Hormone

Condition Hierarchy (Ancestors)

Hypogonadism; Gonadal Disorders; Endocrine System Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Nutritional and Metabolic Diseases; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Central Study Contacts

Michael O' Reilly, FRCPI PhD

CONTACT

018093894; michaelworeilly@rcsi.ie

Clare Miller, MBBS

CONTACT

0857509379; claremiller22@rcsi.com

Study Design

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

Study Record Dates

• First Submitted: March 6, 2023
• First Posted: March 17, 2023
• Study Start: March 12, 2023
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2024
• Last Updated: March 17, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

IE (1)