Sex Steroids Balance for Metabolic and Reproductive Health in Klinefelter Syndrome

NCT05586802 | Recruiting Phase 3

• 1 other identifier: PZ00P3_202151
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

The study seeks primarily to determine whether modulation of systemic and testicular sex steroids balance by aromatase inhibitors will positively affect the metabolic health and spermatogenesis of men with Klinefelter syndrome (KFS) as compared to the current state of the art for each issue. Secondary objectives of this study are (i) to unravel the heterogeneity of the reproductive and metabolic phenotype of men with KFS by performing a multi-omic analysis in a large cohort at baseline; (ii) to evaluate the efficacy of semaglutide-induced weight loss to achieve metabolic and reproductive benefit in men with Klinefelter syndrome as compared to standard testosterone replacement; (ii) to assess whether addition of hCG to aromatase inhibitors further increases intratesticular testosterone and promotes spermatogenesis in men with KFS.

Conditions

Klinefelter Syndrome

Keywords

Metabolic syndrome; Infertility; Aromatase; Testosterone/estradiol ratio; mTESE biopsy; GLP1 agonists

Outcome Measures

Primary Outcomes (2)

• Design 1 : sperm retrieval rate at mTESE biopsy

  Sperm retrieval rate at mTESE biopsy (Group A and B)

  mTESE biopsy 26 weeks after hormonal intervention

• Design 2 : change in insulin resistance index (HOMA-IR)

  HOMA-IR calculated using fasting glucose and insulin levels

  From baseline to week 26 of intervention

Study Arms (6)

Group 1 (Fertility) - positive micro-dissection testicular sperm extraction (mTESE) biopsy 1

NO INTERVENTION

Men with Klinefelter syndrome seeking fertility or interested in fertility preservation that undergo mTESE biopsy after wash-out of testosterone replacement therapy and have positive sperm retrieval (detectable spermatozoids)

Group 1 (Fertility) - negative mTESE biopsy 1, then randomized to Arm A

EXPERIMENTAL

Men with Klinefelter syndrome seeking fertility or interested in fertility preservation that undergo mTESE biopsy after wash-out of testosterone replacement therapy and have negative sperm retrieval (no detectable spermatozoids), subsequently randomized to receive an hormonal stimulation for 26 weeks

Drug: Anastrozole

Group 1 (Fertility) - negative mTESE biopsy 1, then randomized to Arm B

EXPERIMENTAL

Men with Klinefelter syndrome seeking fertility or interested in fertility preservation that undergo mTESE biopsy after wash-out of testosterone replacement therapy and have negative sperm retrieval (no detectable spermatozoids), subsequently randomized to receive an hormonal stimulation for 26 weeks

Drug: Anastrozole; Drug: human chorionic gonadotropin

Group 2 (Metabolic Risk) - randomized to Arm C

ACTIVE COMPARATOR

Men with Klinefelter syndrome not interested in fertility that present with high metabolic risk and consent to a wash-out of testosterone replacement therapy. They are subsequently randomized to receive an hormonal treatment to improve metabolic health. This arm will receive an active comparator by a testosterone gel

Drug: Testosterone gel

Group 2 (Metabolic Risk) - randomized to Arm D

EXPERIMENTAL

Men with Klinefelter syndrome not interested in fertility that present with high metabolic risk and consent to a wash-out of testosterone replacement therapy. They are subsequently randomized to receive an hormonal treatment to improve metabolic health. This arm will receive an an experimental treatment

Drug: Anastrozole

Group 2 (Metabolic Risk) - randomized to Arm E

EXPERIMENTAL

Men with Klinefelter syndrome not interested in fertility that present with high metabolic risk and consent to a wash-out of testosterone replacement therapy. They are subsequently randomized to receive an hormonal treatment to improve metabolic health. This arm will receive an an experimental treatment

Drug: Semaglutide

Interventions

Anastrozole DRUG

This will be an experimental treatment for 26 weeks in Group 1 Arm A and Arm B as well for Group 2 Arm D

Also known as: Anastrozole Teva

Group 1 (Fertility) - negative mTESE biopsy 1, then randomized to Arm A; Group 1 (Fertility) - negative mTESE biopsy 1, then randomized to Arm B; Group 2 (Metabolic Risk) - randomized to Arm D

Semaglutide DRUG

This will be an experimental treatment for 26 weeks in Group 2 Arm E

Also known as: Ozempic

Group 2 (Metabolic Risk) - randomized to Arm E

human chorionic gonadotropin DRUG

This will be an experimental treatment for 26 weeks in addition to anastrozole in Group 1 - Arm B

Also known as: Choriomon

Group 1 (Fertility) - negative mTESE biopsy 1, then randomized to Arm B

Testosterone gel DRUG

This will be an active comparator for 26 weeks in Group 2 - Arm C

Also known as: Tostran

Group 2 (Metabolic Risk) - randomized to Arm C

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of Klinefelter syndrome (47,XXY or mosaicism)
• Design 1:
• Age range: 16-40 years old
• Intention to become parent or interest in fertility preservation
• Confirmed azoospermia (lack of spermatozoids) after centrifugation of one semen sample
• Design 2:
• Age range: 18-65 years old
• No interest in fertility or fertility preservation
• Hypogonadism at diagnosis or after wash-out of testosterone replacement therapy
• High metabolic risk defined as overweight (BMI 25-28 kg/m2) and insulin resistance (HOMA-IR \> 2.6)

You may not qualify if:

• Contraindications to testosterone-rising therapies (prostate or breast cancer, PSA \> 4 µg/l, active liver disease, symptomatic heart disease)
• Decreased life expectancy due to terminal disease
• Known or suspected non-compliance, drug or alcohol abuse
• Inability to follow the procedures of the study (language problems, severe psychological or mental disorders)

Sponsors & Collaborators

• Georgios Papadakis: lead

Study Sites (1)

Service of Endocrinology, Diabetes & Metabolism

Lausanne, 1011, Switzerland

RECRUITING

MeSH Terms

Conditions

Klinefelter Syndrome; Metabolic Syndrome; Infertility

Interventions

Anastrozole; semaglutide; Chorionic Gonadotropin

Condition Hierarchy (Ancestors)

Sex Chromosome Disorders of Sex Development; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Sex Chromosome Disorders; Chromosome Disorders; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Gonadal Disorders; Endocrine System Diseases; Hypogonadism; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Placental Hormones; Peptides; Amino Acids, Peptides, and Proteins; Pregnancy Proteins; Proteins

Study Officials

• GEORGIOS PAPADAKIS, MD

  Service of endocrinology, diabetes & metabolism, CHUV, Lausanne University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

GEORGIOS PAPADAKIS, MD

CONTACT

+41795560308; georgios.papadakis@chuv.ch

RIKIATOU FRANCIOLI, MD

CONTACT

+41795562861; Rikiatou.Francioli@chuv.ch

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Senior Lecturer (Privat docent & MERclin)

Model Details: Two designs according to the presence of fertility desire (Design 1) or high metabolic risk (Design 2)

Study Record Dates

• First Submitted: October 15, 2022
• First Posted: October 19, 2022
• Study Start: March 21, 2023
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: January 5, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: At study completion

Locations

CH (1)