Klinefelter SyndromePhase 3KLIN-HEALTHNCT05586802
Sex Steroids Balance for Metabolic and Reproductive Health in Klinefelter Syndrome
A Phase 3 study testing Anastrozole, Semaglutide and human chorionic gonadotropin in people with Klinefelter Syndrome, run by Georgios Papadakis at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 to 65 years, men only
- Conditions the study is for
- Klinefelter Syndrome
- What is being tested?
- Anastrozole, Semaglutide and human chorionic gonadotropin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteSwitzerland
- Study dates
- 21 Mar 2023to 30 Apr 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 65 years
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- -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:
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- 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)
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland1 site, 1 recruiting
- Recruiting
Service of Endocrinology, Diabetes & Metabolism
Lausanne, 1011
GEORGIOS PAPADAKIS, PD Dr med, + 41795560308, georgios.papadakis@chuv.ch
About this study
Official title: Dissecting the Importance of Sex Steroids Balance for Metabolic and Reproductive Health in Men With Klinefelter Syndrome: a Randomized Controlled Study
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
- Being tested
- Anastrozole, Semaglutide, human chorionic gonadotropin, Testosterone gel
- Keywords
- Metabolic syndrome, Infertility, Aromatase, Testosterone/estradiol ratio, mTESE biopsy, GLP1 agonists
- Medical subject headings
- Klinefelter Syndrome, Metabolic Syndrome, Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnastrozoleDrug
Also called Anastrozole Teva
This will be an experimental treatment for 26 weeks in Group 1 Arm A and Arm B as well for Group 2 Arm D
SemaglutideDrug
Also called Ozempic
This will be an experimental treatment for 26 weeks in Group 2 Arm E
human chorionic gonadotropinDrug
Also called Choriomon
This will be an experimental treatment for 26 weeks in addition to anastrozole in Group 1 - Arm B
Testosterone gelDrug
Also called Tostran
This will be an active comparator for 26 weeks in Group 2 - Arm C
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: Drug: Semaglutide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Design 1 : sperm retrieval rate at mTESE biopsy
Sperm retrieval rate at mTESE biopsy (Group A and B)
Measured: 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
Measured: From baseline to week 26 of intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2022
- Study start21 Mar 2023
- Primary completion30 Apr 2027 (estimated)
- Study completion30 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Klinefelter SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Two designs according to the presence of fertility desire (Design 1) or high metabolic risk (Design 2)
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Georgios Papadakis
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Georgios Papadakis, University of Lausanne Hospitals
- Investigators
- GEORGIOS PAPADAKIS, MD, Principal investigator, Service of endocrinology, diabetes & metabolism, CHUV, Lausanne University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05586802
- Sponsor's protocol ID
- PZ00P3_202151
- Acronym
- KLIN-HEALTH
- Status last verified
- May 2026
- First submitted
- 15 Oct 2022
- Last updated
- 11 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Upon reasonable request and data transfer agreement