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Sex Steroids Balance for Metabolic and Reproductive Health in Klinefelter Syndrome (KLIN-HEALTH)

Primary Purpose

Klinefelter Syndrome

Status
Recruiting
Phase
Phase 3
Locations
Switzerland
Study Type
Interventional
Intervention
Anastrozole
Semaglutide
human chorionic gonadotropin
Testosterone gel
Sponsored by
Georgios Papadakis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Klinefelter Syndrome focused on measuring Metabolic syndrome, Infertility, Aromatase, Testosterone/estradiol ratio, mTESE biopsy, GLP1 agonists

Eligibility Criteria

16 Years - 65 Years (Child, Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

-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 2 semen samples

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 severe overweight (BMI ≥ 28 kg/m2) or BMI 25-28 kg/m2 with insulin resistance (HOMA-IR > 2.6)

Exclusion Criteria:

  • 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)

Sites / Locations

  • Service of Endocrinology, Diabetes & MetabolismRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

No Intervention

Experimental

Experimental

Active Comparator

Experimental

Experimental

Arm Label

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

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

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

Design 2 (Metabolic Risk) - randomized to Group C

Design 2 (Metabolic Risk) - randomized to Group D

Design 2 (Metabolic Risk) - randomized to Group E

Arm Description

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)

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

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

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

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

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

Outcomes

Primary Outcome Measures

Design 1 : sperm retrieval rate at mTESE biopsy
Sperm retrieval rate at mTESE biopsy (Group A and B)
Design 2 : change in insulin resistance index (HOMA-IR)
HOMA-IR calculated using fasting glucose and insulin levels

Secondary Outcome Measures

Full Information

First Posted
October 15, 2022
Last Updated
April 20, 2023
Sponsor
Georgios Papadakis
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1. Study Identification

Unique Protocol Identification Number
NCT05586802
Brief Title
Sex Steroids Balance for Metabolic and Reproductive Health in Klinefelter Syndrome
Acronym
KLIN-HEALTH
Official Title
Dissecting the Importance of Sex Steroids Balance for Metabolic and Reproductive Health in Men With Klinefelter Syndrome: a Randomized Controlled Study
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 21, 2023 (Actual)
Primary Completion Date
April 1, 2026 (Anticipated)
Study Completion Date
April 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Georgios Papadakis

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Klinefelter Syndrome
Keywords
Metabolic syndrome, Infertility, Aromatase, Testosterone/estradiol ratio, mTESE biopsy, GLP1 agonists

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Two designs according to the presence of fertility desire (Design 1) or high metabolic risk (Design 2)
Masking
None (Open Label)
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Design 1 (Fertility) - positive micro-dissection testicular sperm extraction (mTESE) biopsy 1
Arm Type
No Intervention
Arm Description
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)
Arm Title
Design 1 (Fertility) - negative mTESE biopsy 1, then randomized to Group A
Arm Type
Experimental
Arm Description
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
Arm Title
Design 1 (Fertility) - negative mTESE biopsy 1, then randomized to Group B
Arm Type
Experimental
Arm Description
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
Arm Title
Design 2 (Metabolic Risk) - randomized to Group C
Arm Type
Active Comparator
Arm Description
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
Arm Title
Design 2 (Metabolic Risk) - randomized to Group D
Arm Type
Experimental
Arm Description
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
Arm Title
Design 2 (Metabolic Risk) - randomized to Group E
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Anastrozole
Other Intervention Name(s)
Anastrozole Teva
Intervention Description
This will be an experimental treatment for 26 weeks in Design 1 Group A and Group B as well for Design 2 Group D
Intervention Type
Drug
Intervention Name(s)
Semaglutide
Other Intervention Name(s)
Ozempic
Intervention Description
This will be an experimental treatment for 26 weeks in Design 2 Group E
Intervention Type
Drug
Intervention Name(s)
human chorionic gonadotropin
Other Intervention Name(s)
Choriomon
Intervention Description
This will be an experimental treatment for 26 weeks in addition to anastrozole in Design 1 -Group B
Intervention Type
Drug
Intervention Name(s)
Testosterone gel
Other Intervention Name(s)
Tostran
Intervention Description
This will be an active comparator for 26 weeks in Design 2 - Group C
Primary Outcome Measure Information:
Title
Design 1 : sperm retrieval rate at mTESE biopsy
Description
Sperm retrieval rate at mTESE biopsy (Group A and B)
Time Frame
mTESE biopsy 26 weeks after hormonal intervention
Title
Design 2 : change in insulin resistance index (HOMA-IR)
Description
HOMA-IR calculated using fasting glucose and insulin levels
Time Frame
From baseline to week 26 of intervention

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: -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 2 semen samples 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 severe overweight (BMI ≥ 28 kg/m2) or BMI 25-28 kg/m2 with insulin resistance (HOMA-IR > 2.6) Exclusion Criteria: 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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
GEORGIOS PAPADAKIS, MD
Phone
+41795560308
Email
georgios.papadakis@chuv.ch
First Name & Middle Initial & Last Name or Official Title & Degree
RIKIATOU FRANCIOLI, MD
Phone
+41795562861
Email
Rikiatou.Francioli@chuv.ch
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GEORGIOS PAPADAKIS, MD
Organizational Affiliation
Service of endocrinology, diabetes & metabolism, CHUV, Lausanne University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Service of Endocrinology, Diabetes & Metabolism
City
Lausanne
ZIP/Postal Code
1011
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
GEORGIOS PAPADAKIS, PD Dr med
Phone
+ 41795560308
Email
georgios.papadakis@chuv.ch

12. IPD Sharing Statement

Learn more about this trial

Sex Steroids Balance for Metabolic and Reproductive Health in Klinefelter Syndrome

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