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
- Are there results?
- Not yet: the study is under way
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:
Show all 10Show fewer
- 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
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dissecting the Importance of Sex Steroids Balance for Metabolic and Reproductive Health in Men With Klinefelter Syndrome: a Randomized Controlled Study
- ClinicalTrials.gov ID
- NCT05586802
- Acronym / sponsor ID
- KLIN-HEALTH / PZ00P3_202151
- Conditions
- Klinefelter Syndrome
- Keywords
- Metabolic syndrome, Infertility, Aromatase, Testosterone/estradiol ratio, mTESE biopsy, GLP1 agonists
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Georgios PapadakisUniversity, hospital or other
- Study start
- 21 Mar 2023 (actual)
- Primary completion
- 30 Apr 2027 (estimated)
- Study completion
- 30 Apr 2027 (estimated)
- First posted
- 19 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
- Model description
- Two designs according to the presence of fertility desire (Design 1) or high metabolic risk (Design 2)
| Arm | Type | Receives |
|---|---|---|
| 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 | Drug: AnastrozoleMen 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 |
| Group 1 (Fertility) - negative mTESE biopsy 1, then randomized to Arm B | Experimental | Drug: Anastrozole, Drug: human chorionic gonadotropinMen 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 |
| Group 2 (Metabolic Risk) - randomized to Arm C | Active comparator | Drug: Testosterone gelMen 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 |
| Group 2 (Metabolic Risk) - randomized to Arm D | Experimental | Drug: AnastrozoleMen 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 |
| Group 2 (Metabolic Risk) - randomized to Arm E | Experimental | Drug: SemaglutideMen 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 |
Who may qualify
- Ages
- 16 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- -Diagnosis of Klinefelter syndrome (47,XXY or mosaicism)
- 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
- Age range: 18-65 years old
Key exclusion criteria (4 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AnastrozoleAlso: Anastrozole TevaThis will be an experimental treatment for 26 weeks in Group 1 Arm A and Arm B as well for Group 2 Arm D | Drug | 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 |
| SemaglutideAlso: OzempicThis will be an experimental treatment for 26 weeks in Group 2 Arm E | Drug | Group 2 (Metabolic Risk) - randomized to Arm E |
| human chorionic gonadotropinAlso: ChoriomonThis will be an experimental treatment for 26 weeks in addition to anastrozole in Group 1 - Arm B | Drug | Group 1 (Fertility) - negative mTESE biopsy 1, then randomized to Arm B |
| Testosterone gelAlso: TostranThis will be an active comparator for 26 weeks in Group 2 - Arm C | Drug | Group 2 (Metabolic Risk) - randomized to Arm C |
Primary outcome
Design 1 : sperm retrieval rate at mTESE biopsy
Time frame: mTESE biopsy 26 weeks after hormonal intervention
Sperm retrieval rate at mTESE biopsy (Group A and B)
Design 2 : change in insulin resistance index (HOMA-IR)
Time frame: From baseline to week 26 of intervention
HOMA-IR calculated using fasting glucose and insulin levels
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2026.
- Individual participant dataSharing planned: Yes. Upon reasonable request and data transfer agreement
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
GEORGIOS PAPADAKIS, MD principal investigator
Service of endocrinology, diabetes & metabolism, CHUV, Lausanne University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact GEORGIOS PAPADAKIS, MD (+41795560308, georgios.papadakis@chuv.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Design 1 : sperm retrieval rate at mTESE biopsy (time frame: mTESE biopsy 26 weeks after hormonal intervention). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2026.