Drepanocytic Men Treated by Hydroxyurea for the First TimePhase 4HYDREPNCT01609192
Future of Spermatogenesis in Men With Sickle Cell Disease Medically Treated
A Phase 4 study testing Hydrea® (hydroxyurea ) in people with Drepanocytic Men Treated by Hydroxyurea for the First Time, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The project's background: Sickle cell disease is, at present in France, the most frequent genetic illness. Recent progress in its treatment, in particular the use of hydroxyurea, has considerably modified the prognosis of this disease. Many more patients now reach reproductive age and do consider fathering. Read more about this study
- Who is it for?
- Ages 18 to 60 years, men only
- Conditions the study is for
- Drepanocytic Men Treated by Hydroxyurea for the First Time
- What is being tested?
- Hydrea® (hydroxyurea )
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteFrance
- Study dates
- Apr 2010to Feb 2013
- Phase
- Phase 4
- 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 60 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- Men from 18 to 60 years old
- Patients diagnosed with sickle-cell anemia homozygote or S beta thal
- Patients for whom a treatment by hydroxyurea is prescribed for the first time.
- Patients having signed the informed consent
- Patients with social security
Who cannot join
- Patients already subjected to a treatment potentially sterilizing
- Patients under supervision or guardianship
- Patients that must begin or stop(arrest) a transfusional program between the beginning of the hydroxyurea and the spermogram in 6 months of treatment.
- Rate of ferritin > 2500 µg/l
Trial locations and contacts
1 site in 1 country.
France1 site
Department of biology of reproduction (TENON Hospital- AP-HP)
Paris, France, 75020
About this study
Official title: Future of Spermatogenesis in Men With Sickle Cell Disease Medically Treated.
The project's background: Sickle cell disease is, at present in France, the most frequent genetic illness. Recent progress in its treatment, in particular the use of hydroxyurea, has considerably modified the prognosis of this disease. Many more patients now reach reproductive age and do consider fathering. Exceptional studies have reported the potential impact of this medical treatment on the sperm parameters and fertility of male patients. In a retrospective analysis, the investigators found that the observed alterations of semen parameters due to sickle cell disease seem to be exacerbated by hydroxyurea treatment.
The study hypothesis: A large prospective study is essential to assess the potential adverse impact of the medical treatment of sickle cell disease on spermatogenesis and consider the advisability of proposing sperm cryopreservation before this treatment is started.
Primary purpose of the protocol: evaluate the impact of a treatment by hydroxyurea (20-30 mg/kg/day), 6 months after its beginning, in 34 men with sickle cell disease (18-60 years old). The main trial criterion will be the average difference of the concentration of spermatozoa s (millions/ml) in the ejaculate, before and after 6 months of medical treatment.
Read the detailed description
Purpose of the study
Sickle cell disease is, at present in France, the most frequent genetic illness. Recent progress in its treatment, in particular the use of hydroxyurea, has considerably modified the prognosis of this disease. Many more patients now reach reproductive age and do consider fathering. Exceptional studies have reported the potential impact of this medical treatment on the sperm parameters and fertility of male patients. In a retrospective analysis, the investigators found that the observed alterations of semen parameters due to sickle cell disease seem to be exacerbated by hydroxyurea treatment. Moreover, after hydroxyurea cessation, while global results in 30 patients were not statistically different before and after hydroxyurea treatment, in four individuals follow-up sperm parameters did not seem to recover quickly and the total number of spermatozoa per ejaculate fell below the normal range in about half the cases.
Therefore, a large prospective study is essential to assess the potential adverse impact of the medical treatment of sickle cell disease on spermatogenesis and consider the advisability of proposing sperm cryopreservation before this treatment is started.
Main outcomes
Evaluate the impact of a treatment by hydroxyurea (20-30 mg/kg/day), 6 months after its beginning, in 34 men with sickle cell disease (18-60 years old). The primary outcome will be the average difference of the concentration of spermatozoa s (millions/ml) in the ejaculate, before and after 6 months of medical treatment. Six months represent 2 complete cycles of spermatogenesis.
The secondary outcomes will be the other sperm parameters: vitality, mobility, motility, morphology of spermatozoa and the assessment of sperm nuclear DNA fragmentation by TUNEL assay (terminal deoxynucleotidyl transferase dUTP nick end labelling).
This prospective, multicenter, cohort study should allow evaluating the impact of a treatment by hydroxyurea on spermatogenesis in men with sickle cell anemia.
With the hypothesis of a five time reduction in spermatozoa concentration (38 millions ± 43 before treatment), at least 34 analyzable patients are required (aged 18 to 60 years old) who have never received any compound known to be toxic for spermatogenesis.
Protocol
Drepanocytic men who are eligible for a first treatment by hydroxyurea will be sent to the CECOS (center for the study and cryopreservation of oocytes and spermatozoa) at Tenon, Cochin or Jean Verdier hospitals. Their medical history will be recorded and sperm parameters will be analyzed according to WHO criteria. Part of the ejaculate will be fixed and stored (- 20°C) for further DNA fragmentation assay. The rest of the semen could be cryopreserved, according to the patients' will, in case of a potential deleterious effect of the medical treatment on male fertility. Six months after the beginning of the treatment by hydroxyurea, another sperm recovery will be required for the same analysis and the already described parameters will be evaluated and compared to initial results.
Prospects
The study should bring valuable data on the effects of hydroxyurea on human spermatogenesis. If any significant impairment is observed, it would be recommended to perform sperm cryopreservation before the treatment's start.
The study could also help to distinguish between the detrimental effects due to the acute adverse events of sickle cell disease itself and those linked to the administration of hydroxyurea.
- Being tested
- Hydrea® (hydroxyurea )
- Keywords
- sickle-cell anemia, spermatogenesis, hydroxyurea
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydrea® (hydroxyurea )Drug
treatment by hydroxyurea (20-30 mg/kg/day) for 6 months
| Study group | Role | What they receive |
|---|---|---|
| hydroxyurea | Experimental | Not described Receives: Drug: Hydrea® (hydroxyurea ) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcomes will be the average difference of the concentration of spermatozoa in the ejaculate measured before treatment and after 6 months of treatment.
Measured: 6 months
Secondary outcomes (4)
the average difference of the sperm DNA fragmentation in the ejaculate measured before treatment and after 6 months of treatment.
Measured: 6 months
the average difference of the mobility of spermatozoa in the ejaculate measured before treatment and after 6 months of treatment.
Measured: 6 months
the average difference of the vitality of spermatozoa in the ejaculate measured before treatment and after 6 months of treatment.
Measured: 6 months
the average difference of the morphology of spermatozoa in the ejaculate measured before treatment and after 6 months of treatment.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2012 (estimated)
- Study startApr 2010
- Primary completionFeb 2013
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Drepanocytic Men Treated by Hydroxyurea for the First TimeStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jacqueline Mandelbaum, Dr, Principal investigator, Assistance Publique
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01609192
- Sponsor's protocol ID
- P 081227
- Other IDs
- AOM 09154
- Acronym
- HYDREP
- Status last verified
- Aug 2013
- First submitted
- 25 Apr 2012
- Last updated
- 7 Aug 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Future of Spermatogenesis in Men With Sickle Cell Disease Medically Treated.
- ClinicalTrials.gov ID
- NCT01609192
- Acronym / sponsor ID
- HYDREP / P 081227
- Keywords
- sickle-cell anemia, spermatogenesis, hydroxyurea
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Apr 2010
- Primary completion
- Feb 2013 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 31 May 2012 (estimated)
- 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 project's background: Sickle cell disease is, at present in France, the most frequent genetic illness. Recent progress in its treatment, in particular the use of hydroxyurea, has considerably modified the prognosis of this disease. Many more patients now reach reproductive age and do consider fathering. Exceptional studies have reported the potential impact of this medical treatment on the sperm parameters and fertility of male patients. In a retrospective analysis, the investigators found that the observed alterations of semen parameters due to sickle cell disease seem to be exacerbated by hydroxyurea treatment.
The study hypothesis: A large prospective study is essential to assess the potential adverse impact of the medical treatment of sickle cell disease on spermatogenesis and consider the advisability of proposing sperm cryopreservation before this treatment is started.
Primary purpose of the protocol: evaluate the impact of a treatment by hydroxyurea (20-30 mg/kg/day), 6 months after its beginning, in 34 men with sickle cell disease (18-60 years old). The main trial criterion will be the average difference of the concentration of spermatozoa s (millions/ml) in the ejaculate, before and after 6 months of medical treatment.
Detailed description
Purpose of the study
Sickle cell disease is, at present in France, the most frequent genetic illness. Recent progress in its treatment, in particular the use of hydroxyurea, has considerably modified the prognosis of this disease. Many more patients now reach reproductive age and do consider fathering. Exceptional studies have reported the potential impact of this medical treatment on the sperm parameters and fertility of male patients. In a retrospective analysis, the investigators found that the observed alterations of semen parameters due to sickle cell disease seem to be exacerbated by hydroxyurea treatment. Moreover, after hydroxyurea cessation, while global results in 30 patients were not statistically different before and after hydroxyurea treatment, in four individuals follow-up sperm parameters did not seem to recover quickly and the total number of spermatozoa per ejaculate fell below the normal range in about half the cases.
Therefore, a large prospective study is essential to assess the potential adverse impact of the medical treatment of sickle cell disease on spermatogenesis and consider the advisability of proposing sperm cryopreservation before this treatment is started.
Main outcomes
Evaluate the impact of a treatment by hydroxyurea (20-30 mg/kg/day), 6 months after its beginning, in 34 men with sickle cell disease (18-60 years old). The primary outcome will be the average difference of the concentration of spermatozoa s (millions/ml) in the ejaculate, before and after 6 months of medical treatment. Six months represent 2 complete cycles of spermatogenesis.
The secondary outcomes will be the other sperm parameters: vitality, mobility, motility, morphology of spermatozoa and the assessment of sperm nuclear DNA fragmentation by TUNEL assay (terminal deoxynucleotidyl transferase dUTP nick end labelling).
This prospective, multicenter, cohort study should allow evaluating the impact of a treatment by hydroxyurea on spermatogenesis in men with sickle cell anemia.
With the hypothesis of a five time reduction in spermatozoa concentration (38 millions ± 43 before treatment), at least 34 analyzable patients are required (aged 18 to 60 years old) who have never received any compound known to be toxic for spermatogenesis.
Protocol
Drepanocytic men who are eligible for a first treatment by hydroxyurea will be sent to the CECOS (center for the study and cryopreservation of oocytes and spermatozoa) at Tenon, Cochin or Jean Verdier hospitals. Their medical history will be recorded and sperm parameters will be analyzed according to WHO criteria. Part of the ejaculate will be fixed and stored (- 20°C) for further DNA fragmentation assay. The rest of the semen could be cryopreserved, according to the patients' will, in case of a potential deleterious effect of the medical treatment on male fertility. Six months after the beginning of the treatment by hydroxyurea, another sperm recovery will be required for the same analysis and the already described parameters will be evaluated and compared to initial results.
Prospects
The study should bring valuable data on the effects of hydroxyurea on human spermatogenesis. If any significant impairment is observed, it would be recommended to perform sperm cryopreservation before the treatment's start.
The study could also help to distinguish between the detrimental effects due to the acute adverse events of sickle cell disease itself and those linked to the administration of hydroxyurea.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| hydroxyurea | Experimental | Drug: Hydrea® (hydroxyurea ) |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Men from 18 to 60 years old
- Patients diagnosed with sickle-cell anemia homozygote or S beta thal
- Patients for whom a treatment by hydroxyurea is prescribed for the first time.
- Patients having signed the informed consent
- Patients with social security
Key exclusion criteria (4 listed)
- Patients already subjected to a treatment potentially sterilizing
- Patients under supervision or guardianship
- Patients that must begin or stop(arrest) a transfusional program between the beginning of the hydroxyurea and the spermogram in 6 months of treatment.
- Rate of ferritin > 2500 µg/l
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 |
|---|---|---|
| Hydrea® (hydroxyurea )treatment by hydroxyurea (20-30 mg/kg/day) for 6 months | Drug | hydroxyurea |
Primary outcome
The primary outcomes will be the average difference of the concentration of spermatozoa in the ejaculate measured before treatment and after 6 months of treatment.
Time frame: 6 months
4 secondary outcomes
the average difference of the sperm DNA fragmentation in the ejaculate measured before treatment and after 6 months of treatment.
Time frame: 6 months
the average difference of the mobility of spermatozoa in the ejaculate measured before treatment and after 6 months of treatment.
Time frame: 6 months
the average difference of the vitality of spermatozoa in the ejaculate measured before treatment and after 6 months of treatment.
Time frame: 6 months
the average difference of the morphology of spermatozoa in the ejaculate measured before treatment and after 6 months of treatment.
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2013.
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.
Jacqueline Mandelbaum, Dr principal investigator
Assistance Publique
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Hydrea® (hydroxyurea ) in people with Drepanocytic Men Treated by Hydroxyurea for the First Time, run by Assistance Publique - Hôpitaux de Paris 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 5 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: finished, as of the sponsor's last update on 7 Aug 2013. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The primary outcomes will be the average difference of the concentration of spermatozoa in the ejaculate measured before treatment and after 6 months of treatment. (time frame: 6 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 7 Aug 2013.