Azoospermia, NonobstructivePhase 3CLOMINOANCT03615547
Interest of Clomiphene Citrate in Patients With Non-obstructive Azoospermia on the Quantity of Sperm Cells
A Phase 3 study testing Clomifene Citrate in people with Azoospermia, Nonobstructive, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
In the absence of sperm in the semen (azoospermia), there is no chance of natural paternity. It is found in about 1% of men and is either due to an obstruction of the seminal tracks (obstructive azoospermia (OA)) in 1/3 of the cases, or a spermatogenic failure (non-obstructive azoospermia (NOA)) in 2/3 of the cases. Read more about this study
- Who is it for?
- Ages 18 to 55 years, men only
- Conditions the study is for
- Azoospermia, Nonobstructive
- What is being tested?
- Clomifene Citrate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteFrance
- Study dates
- Jan 2026to Jan 2029
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 18 to 55 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- Patient aged from 18-55
- Body Mass Index lower than 35
- Patients with confirmed diagnostic of Non Obstructive Azoospermia based on
- 2 negative spermogram with centrifugation (three month in between)
- Failure of detecting spermatozoid at first testicular sperm extraction (TESE)
- Patients without sperm cells at semen analysis
- Signed informed consent
- Patients benefiting from a social insurance system or a similar system
Who cannot join
- Patients with grade 2 or 3 varicocele, persistant after cure of the varicocele.
- Patients with current or history of testicular tumor detected on a less than 3 months' ultrasound.
- Patients with history of any other cancer of less than 5 years.
- Patient with Klinefelter or karyotype abnormalities
- Yq micro-deletions
- First TESE conducted under hormonal treatment (Clomifene, Tamoxifen, gonadotrophins or anti-aromatase)
Show all 14Show fewer
- Patients receiving a treatment known to alter male fertility (see RCP of the treatment, colchicine, methotrexate, ….) in the 6 months before inclusion.
- Patients receiving treatment know to modify the gonadotroph axis activity (FSH, TESTO, DHT, HCG…)
- Hypogonadotropic Hypogonadism
- Persistant bilateral abdominal cryptorchidism
- Patient unable to understand the purpose of the trial or refusing to follow treatment and post-treatment instructions
- Patients with history of psychiatric disorder
- Participation to another trial that would interfere with this trial
- Patients under legal protection
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Interest of Clomiphene Citrate (CC) Associated With a Second Testicular Sperm Extraction (TESE) in Patients With Non-obstructive Azoospermia (NOA) After Failure of a First TESE, on the Quantity of Sperm Cells Available for Intracytoplasmic Sperm Injection (ICSI). Randomized Double Blind Trial Versus Placebo.
In the absence of sperm in the semen (azoospermia), there is no chance of natural paternity. It is found in about 1% of men and is either due to an obstruction of the seminal tracks (obstructive azoospermia (OA)) in 1/3 of the cases, or a spermatogenic failure (non-obstructive azoospermia (NOA)) in 2/3 of the cases. To date, no medical treatment had proved its efficiency to induce spermatogenesis in case of NOA.
The development of Intracytoplasmic sperm injection (ICSI) in 1992 allowed to obtain pregnancies from a small number of spermatozoa. The next year, testicular sperms were extracted from testicular tissue obtained surgically in cases of OA , allowing paternity for azoospermic men. In case of NOA, TESE allowed to obtain few sperms in an unexpected number of cases. It was shown that spermatogenesis remains active in rare portions of seminiferous tubules, a phenomenon called focal spermatogenesis, which allows to extract testicular sperms with an average SRR of 50%, and to obtain pregnancy by ICSI. Thus, TESE-ICSI revolutionized the prognosis of NOA, however, half of the cases of NOA had no sperm extracted and remained sterile . Since sperm donation and adoption are unacceptable for several of these couples, there is a real demand for additional treatment.
Read more
Two ways to improve chances of paternity in case of NOA are currently discussed:
- Proceed to a second attempt of TESE. Since the first attempt could have missed a focus of active spermatogenesis, the chance for a positive second TESE is not null even. Reviewing the few articles published on this issue , the SRR for the second attempt, after a first negative attempt averaged 25%.
- Based upon the decrease of testosterone production within the testis in case of NOA and the potential increased of the focal spermatogenesis by gonadotropins, few reports of hormonal therapy in case of NOA have been published and suggested a positive effect of hormonal therapy.
This prompted us to develop this clinical trial to investigate the effect of Clomiphene Citrate versus placebo on the results of a second TESE in NOA.
Results of hormonal therapy in case of NOA were heterogeneous and of poor methodological quality, none was randomized versus placebo: Anti-aromatases or Gonadotropins administered before the first TESE or the second TESE gave positive results. Hussein at al in 2013, suggested a positive effect of Clomiphene citrate (CC), administrated before the first TESE (57% of the CC treated group versus 33.6% in not treated group) but with drop out of patient positive to sperm analysis. However, in these positive studies, sample sizes were small or selected patients on hormonal status or histology criteria suggesting subgroup of favourable NOA. Thus, there is no strong evaluation of the interest of hormonal treatment in NOA, after a negative first TESE.
The investigators decided to evaluate the effect of the CC, the most convincing and convenient hormonal treatment, in patients with negative first TESE for NOA. It is of main interest to known if CC could enhance the SRR of a second TESE, that is the ultimate possibility to have their own child for these patients.
- Conditions
- Azoospermia, Nonobstructive
- Being tested
- Clomifene Citrate, Placebo
- Keywords
- azoospermia, clominophene
- Medical subject headings
- Azoospermia, Nonobstructive, Azoospermia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clomifene CitrateDrug
After randomization, the andrologist will give a prescription with the first three months of treatment (Clomifene Citrate or placebo) to be collected to the local hospital pharmacy. The andrologist will be blind of the treatment arm.
Treatment unit and their shipment to local pharmacy will be provided and organized by the East group pharmacy of the Hospices Civils of Lyon which is the coordination pharmacy for this study. Prescription and delivery will be renewed for three months at the 3 month and 6 months visit.
The experimental treatment consists in a daily dose of 50mg of Clomifene Citrate per os during 9 months followed by a second TESE if no spermatozoid has been obtained from semen. The dose level was set according to Chua et al 2013 (cf 1.2.2). One capsule containing 50 mg of CC will be orally administered in the morning every day.
PlaceboOther
The placebo treatment consists in a daily dose of 50mg of lactose monohydrate per os during 9 months followed by a second TESE if no spermatozoid has been obtained from semen. The capsule containing the placebo will have the exact same size, weight, color, taste and will be delivered in the exact same condition as the experimental treatment capsule.
| Study group | Role | What they receive |
|---|---|---|
| Clomifene citrate group | Experimental | a daily dose of 50mg of Clomifene Citrate per os during 9 months Receives: Drug: Clomifene Citrate |
| Placebo group | Experimental | a daily dose of 50mg per os of placebo (lactose monohydrate) during 9 months. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
presence of sperm cells point of view
Evaluate, versus placebo, the interest of 9 months treatment by 50 mg of Clomiphene citrate to increase the proportion of patient for which at least one sperm cell can be isolated either from the semen at 9 months of treatment or, in case of persistent azoospermia, from a second TESE attempt performed at 9 months of treatment
Measured: 9 months
Secondary outcomes (17)
number of sperm cells point of view
Evaluate, versus placebo, the interest of 9 months treatment by 50 mg of Clomiphene citrate to increase the number of spermatozoa obtained, from the semen at 9 months of treatment or, in case of persistent azoospermia, from a second TESE attempt performed at 9 months of treatment
Measured: 9 months
Follicle Stimulating Hormone (FSH) level evolution
Evaluate the evolution of FSH in both groups
Measured: 9 months
testosterone level evolution
Evaluate the evolution of testosterone in both groups
Measured: 9 months
Luteinizing hormone (LH) level evolution
Evaluate the evolution of LH in both groups
Measured: 9 months
Sex Hormone-Binding Globulin (SHBG) level evolution
Evaluate the evolution of SHBG in both groups
Measured: 9 months
Bioavailable testosterone Inhibin B level evolution
Evaluate the evolution of bioavailable testosterone Inhibin B in both groups
Measured: 9 months
number spermatogonia
Evaluate Hypospermatogenesis status
Measured: 9 months
number of spermatocytes,
Evaluate Hypospermatogenesis status
Measured: 9 months
number of round elongated spermatids
Evaluate Hypospermatogenesis status
Measured: 9 months
prevalence of Sertoli cell only syndrome
Evaluate Sertoli cell only syndrome status
Measured: 9 months
prevalence of maturation arrest
Evaluate maturation arrest status
Measured: 9 months
number of Clomiphene citrate capsules
Compliance will be measured by counting the number of Clomiphene citrate capsules remaining in the brought back at each visit
Measured: 9 months
number of adverse events
Evolution of Clomiphene citrate proportion of side effects
Measured: 9 months
proportion of complications at the second TESE
Measured: 9 months
proportion of Pregnancies
proportion of pregnancies after Intracytoplasmic sperm injection
Measured: 9 months
proportion of Miscarriages
proportion of Miscarriages after ICSI
Measured: 9 months
number of Newborn
proportion of Newborn after ICSI
Measured: 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2018
- Study startJan 2026 (estimated)
- Primary completionJan 2029 (estimated)
- Study completionJan 2029 (estimated)
Why it stopped: problems of feasibility
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Azoospermia, NonobstructiveStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- 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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Plotton Ingrid, Principal investigator, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03615547
- Sponsor's protocol ID
- 69HCL18_0033
- Acronym
- CLOMINOA
- Status last verified
- Jun 2026
- First submitted
- 20 Jul 2018
- Last updated
- 17 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Interest of Clomiphene Citrate (CC) Associated With a Second Testicular Sperm Extraction (TESE) in Patients With Non-obstructive Azoospermia (NOA) After Failure of a First TESE, on the Quantity of Sperm Cells Available for Intracytoplasmic Sperm Injection (ICSI). Randomized Double Blind Trial Versus Placebo.
- ClinicalTrials.gov ID
- NCT03615547
- Acronym / sponsor ID
- CLOMINOA / 69HCL18_0033
- Conditions
- Azoospermia, Nonobstructive
- Keywords
- azoospermia, clominophene
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: problems of feasibility
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- Jan 2026 (estimated)
- Primary completion
- Jan 2029 (estimated)
- Study completion
- Jan 2029 (estimated)
- First posted
- 6 Aug 2018 (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.
In the absence of sperm in the semen (azoospermia), there is no chance of natural paternity. It is found in about 1% of men and is either due to an obstruction of the seminal tracks (obstructive azoospermia (OA)) in 1/3 of the cases, or a spermatogenic failure (non-obstructive azoospermia (NOA)) in 2/3 of the cases. To date, no medical treatment had proved its efficiency to induce spermatogenesis in case of NOA.
The development of Intracytoplasmic sperm injection (ICSI) in 1992 allowed to obtain pregnancies from a small number of spermatozoa. The next year, testicular sperms were extracted from testicular tissue obtained surgically in cases of OA , allowing paternity for azoospermic men. In case of NOA, TESE allowed to obtain few sperms in an unexpected number of cases. It was shown that spermatogenesis remains active in rare portions of seminiferous tubules, a phenomenon called focal spermatogenesis, which allows to extract testicular sperms with an average SRR of 50%, and to obtain pregnancy by ICSI. Thus, TESE-ICSI revolutionized the prognosis of NOA, however, half of the cases of NOA had no sperm extracted and remained sterile . Since sperm donation and adoption are unacceptable for several of these couples, there is a real demand for additional treatment.
Two ways to improve chances of paternity in case of NOA are currently discussed:
- Proceed to a second attempt of TESE. Since the first attempt could have missed a focus of active spermatogenesis, the chance for a positive second TESE is not null even. Reviewing the few articles published on this issue , the SRR for the second attempt, after a first negative attempt averaged 25%.
- Based upon the decrease of testosterone production within the testis in case of NOA and the potential increased of the focal spermatogenesis by gonadotropins, few reports of hormonal therapy in case of NOA have been published and suggested a positive effect of hormonal therapy.
This prompted us to develop this clinical trial to investigate the effect of Clomiphene Citrate versus placebo on the results of a second TESE in NOA.
Results of hormonal therapy in case of NOA were heterogeneous and of poor methodological quality, none was randomized versus placebo: Anti-aromatases or Gonadotropins administered before the first TESE or the second TESE gave positive results. Hussein at al in 2013, suggested a positive effect of Clomiphene citrate (CC), administrated before the first TESE (57% of the CC treated group versus 33.6% in not treated group) but with drop out of patient positive to sperm analysis. However, in these positive studies, sample sizes were small or selected patients on hormonal status or histology criteria suggesting subgroup of favourable NOA. Thus, there is no strong evaluation of the interest of hormonal treatment in NOA, after a negative first TESE.
The investigators decided to evaluate the effect of the CC, the most convincing and convenient hormonal treatment, in patients with negative first TESE for NOA. It is of main interest to known if CC could enhance the SRR of a second TESE, that is the ultimate possibility to have their own child for these patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Clomifene citrate group | Experimental | Drug: Clomifene Citratea daily dose of 50mg of Clomifene Citrate per os during 9 months |
| Placebo group | Experimental | Other: Placeboa daily dose of 50mg per os of placebo (lactose monohydrate) during 9 months. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Patient aged from 18-55
- Body Mass Index lower than 35
- Patients with confirmed diagnostic of Non Obstructive Azoospermia based on
- 2 negative spermogram with centrifugation (three month in between)
- Failure of detecting spermatozoid at first testicular sperm extraction (TESE)
Key exclusion criteria (14 listed)
- Patients with grade 2 or 3 varicocele, persistant after cure of the varicocele.
- Patients with current or history of testicular tumor detected on a less than 3 months' ultrasound.
- Patients with history of any other cancer of less than 5 years.
- Patient with Klinefelter or karyotype abnormalities
- Yq micro-deletions
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 |
|---|---|---|
| Clomifene CitrateAfter randomization, the andrologist will give a prescription with the first three months of treatment (Clomifene Citrate or placebo) to be collected to the local hospital pharmacy. The andrologist will be blind of the treatment arm. Treatment unit and their shipment to local pharmacy will be provided and organized by the East group pharmacy of the Hospices Civils of Lyon which is the coordination pharmacy for this study. Prescription and delivery will be renewed for three months at the 3 month and 6 months visit. The experimental treatment consists in a daily dose of 50mg of Clomifene Citrate per os during 9 months followed by a second TESE if no spermatozoid has been obtained from semen. The dose level was set according to Chua et al 2013 (cf 1.2.2). One capsule containing 50 mg of CC will be orally administered in the morning every day. | Drug | Clomifene citrate group |
| PlaceboThe placebo treatment consists in a daily dose of 50mg of lactose monohydrate per os during 9 months followed by a second TESE if no spermatozoid has been obtained from semen. The capsule containing the placebo will have the exact same size, weight, color, taste and will be delivered in the exact same condition as the experimental treatment capsule. | Other | Placebo group |
Primary outcome
presence of sperm cells point of view
Time frame: 9 months
Evaluate, versus placebo, the interest of 9 months treatment by 50 mg of Clomiphene citrate to increase the proportion of patient for which at least one sperm cell can be isolated either from the semen at 9 months of treatment or, in case of persistent azoospermia, from a second TESE attempt performed at 9 months of treatment
17 secondary outcomes
number of sperm cells point of view
Time frame: 9 months
Follicle Stimulating Hormone (FSH) level evolution
Time frame: 9 months
testosterone level evolution
Time frame: 9 months
Luteinizing hormone (LH) level evolution
Time frame: 9 months
Sex Hormone-Binding Globulin (SHBG) level evolution
Time frame: 9 months
Bioavailable testosterone Inhibin B level evolution
Time frame: 9 months
number spermatogonia
Time frame: 9 months
number of spermatocytes,
Time frame: 9 months
number of round elongated spermatids
Time frame: 9 months
prevalence of Sertoli cell only syndrome
Time frame: 9 months
prevalence of maturation arrest
Time frame: 9 months
number of Clomiphene citrate capsules
Time frame: 9 months
number of adverse events
Time frame: 9 months
proportion of complications at the second TESE
Time frame: 9 months
proportion of Pregnancies
Time frame: 9 months
proportion of Miscarriages
Time frame: 9 months
number of Newborn
Time frame: 9 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2026.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Plotton Ingrid principal investigator
Hospices Civils de Lyon
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 Clomifene Citrate in people with Azoospermia, Nonobstructive, run by Hospices Civils de Lyon at 1 site in France.
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 8 inclusion and 14 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: withdrawn, as of the sponsor's last update on 17 Jun 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 France. 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?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
presence of sperm cells point of view (time frame: 9 months). 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 17 Jun 2026.