Healthy VolunteersPhase 1NCT02094313
Effects of Atorvastatin on Human Semen and Gonadal Hormones
A Phase 1 study testing Atorvastatin in people with Healthy Volunteers and Normocholesterolaemic Men, run by University Hospital, Clermont-Ferrand at 1 site in France.
Trial summary
Recently, concerns about the effect of atorvastatin intake on men fertility have been raised. However, this statin has never been investigated regarding its influence on male fertility, notably sperm quality. Read more about this study
- Who is it for?
- Ages 18 to 65 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers, Normocholesterolaemic Men, Normozoospermic Men
- What is being tested?
- Atorvastatin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteFrance
- Study dates
- Jan 2008to Jan 2014
- Phase
- Phase 1
- 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 65 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Men :
- between 18 and 65 years ;
- with normal conventional semen parameters and negative semen culture according to WHO standards 1999 : volume ejaculate ≥ 2 ml, sperm count ≥ 20millions/ml, total motility ≥ 50% progressive motility ≥ 30%, typical forms ≥ 20%;
- with normal blood lipid profile: total cholesterol < 2.50g/L, triglycerides < 1.70g/L, HDL-C > 0.35 g/L and LDL-C < 2.2 g/L;
- without known pathology or ongoing treatment
Who cannot join
- Subjects with medical or surgical history that may make them at risk during the study,
- Subjects with cons-indications to taking atorvastatin
- Subjects with an active liver disease or increased level of serum transaminases
- Subjects with a history of allergy
- Subjects whose lipid parameters do not match the inclusions criteria or receiving lipid-lowering therapy
- Subject with abnormal semen analysis or cryptorchidism or a varicocele
- Subjects who participated in another clinical trial or other experimentation or other tolerance study of a drug
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Decrease in Cholesterol Levels Induced by a Statin on Sperm Quality
Recently, concerns about the effect of atorvastatin intake on men fertility have been raised. However, this statin has never been investigated regarding its influence on male fertility, notably sperm quality.
The aim of this pilot study is to evaluate the efficacy and the safety of a decrease of cholesterol blood levels, induced by taking atorvastatin, on sperm quality of normocholesterolaemic and healthy men without confounding factors.
Read the detailed description
The main objective is to estimate the safety of atorvastatin on fertility of normocholesterolaemic and healthy men (having normal blood lipid profile and normal sperm parameters) by analyzing its effects on sperm parameters: ejaculate volume, sperm count, total and progressive motility, percentage of typical forms.
The secondary objectives are to assess the changes in:
- hormonal profile: gonadotropins and testosterone plasma levels
- lipid composition of sperm and seminal fluid;
- spermatozoa capacitation markers
- accessory glands markers.
The efficacy is estimated by measuring the lipid lowering action of atorvastatin. It is expected a decrease by 20 and 40% of total cholesterol blood and LDL-cholesterol levels, respectively (total cholesterol <1.5 g / l and LDL-cholesterol <1g / l).
Considering this protocol as a pilot study to evaluate safety and efficacy, sample size estimation was fixed considering a Fleming design at one stage. These designs with one group and multi-stages (between 1 and 5) can be seen as filtering steps leading to the decision type go/no go. With a type I error a and statistical power (1-β) equals respectively 5% and 90%, n=17 subjects were necessary to reject the hypotheses of minimal (p=0.85) and maximal (p=0.95) acceptable non-toxicity. If 1 subject or more presented a toxicity, the treatment was considered no safe. To measure the evolution of total cholesterol and LDL-cholesterol levels concerning the efficacy, n=17 subjects were necessary to show a minimal paired difference (to be detected) of 0.5 with expected standard-deviation of difference = 0.5, correlation coefficient of 0.5, a= 5% (two-sided) for a power greater than 90% (1-β=97%).
Subjects are included after a screening visit (visit 0), during which routine laboratory biochemical tests are performed, an electrocardiogram is taken, blood pressure, weight and height are measured; physical examination including testis evaluation and semen parameters are analyzed according to WHO standards 1999 .
The subjects take atorvastatin orally (10mg/day (d), Tahor©, Pfizer Laboratory) during 5 months allowing to study atorvastatin effects on human spermatogenesis and epididymal maturation (one cycle requiring approximately 3 months).
Blood and semen parameters were measured :
- before to take atorvastatin treatment (visit 1)
- at the end of the therapy (visit 3)
- and 3 months after the end of treatment, (visit 4) to perform measurements during different cycles of spermatogenesis on a same subject. After two months of treatment, a consultation (visit 2) is realized to ensure good tolerance to treatment and to control treatment efficiency.
Biochemical clinical and semen measurements take before treatment were considered as "control baseline measures".
- Being tested
- Atorvastatin
- Keywords
- Atorvastatin, Human Spermatozoa, Seminal fluid, Accessory Glands, Cholesterol, Gonadotropins,, Testosterone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtorvastatinDrug
Also called cholesterol lowering drug
The aim of this pilot study is to evaluate the efficacy and the safety of a decrease of cholesterol blood levels, induced by taking atorvastatin, on sperm quality of normocholesterolaemic and healthy men without confounding factors.
| Study group | Role | What they receive |
|---|---|---|
| atovastatin | Experimental | Not described Receives: Drug: Atorvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Observations of all modifications on semen quality after 5 months of atorvastatin treatment
Measured: at month 5
Observations of all modifications on semen quality after 5 months of atorvastatin treatment and after 3 months after its withdrawal
Measured: at month 8
Secondary outcomes (4)
hormonal profile: gonadotropins and total testosterone plasma levels
All modifications observed after 5 months of atorvastatin therapy and after 3 months after the end of treatment on
Measured: at month 5
lipid composition of sperm and seminal fluid
All modifications observed after 5 months of atorvastatin therapy and after 3 months after the end of treatment on
Measured: at month 5
spermatozoa capacitation markers
All modifications observed after 5 months of atorvastatin therapy and after 3 months after the end of treatment on
Measured: at month 5
accessory glands markers
All modifications observed after 5 months of atorvastatin therapy and after 3 months after the end of treatment on
Measured: at month 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2014 (estimated)
- Study startJan 2008
- Primary completionJan 2014
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by University Hospital, Clermont-FerrandThe 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Clermont-Ferrand
- Sponsor type
- University, hospital or other
- Collaborators
- Service de Biologie de la Reproduction : AMP-CECOS, EA 975, Laboratoire de BDR, Service d'Endocrinologie, Diabète et Maladies Métaboliques, Laboratoire d'Hormonologie - Biochimie
- Responsible party
- Sponsor
- Investigators
- Igor TAUVERON, Principal investigator, University Hospital, Clermont-Ferrand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02094313
- Sponsor's protocol ID
- CHU-0185
- Other IDs
- 2006-004376-12
- Status last verified
- Mar 2014
- First submitted
- 17 Mar 2014
- Last updated
- 21 Mar 2014
- Results posted
- No
Publications
Pons-Rejraji H, Brugnon F, Sion B, Maqdasy S, Gouby G, Pereira B, Marceau G, Gremeau AS, Drevet J, Grizard G, Janny L, Tauveron I. Evaluation of atorvastatin efficacy and toxicity on spermatozoa, accessory glands and gonadal hormones of healthy men: a pilot prospective clinical trial. Reprod Biol Endocrinol. 2014 Jul 12;12:65. doi: 10.1186/1477-7827-12-65.
PubMed 25016482
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Decrease in Cholesterol Levels Induced by a Statin on Sperm Quality
- ClinicalTrials.gov ID
- NCT02094313
- Acronym / sponsor ID
- CHU-0185
- Keywords
- Atorvastatin, Human Spermatozoa, Seminal fluid, Accessory Glands, Cholesterol, Gonadotropins,, Testosterone
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University Hospital, Clermont-FerrandUniversity, hospital or other
- Collaborators
- Service de Biologie de la Reproduction : AMP-CECOS, EA 975, Laboratoire de BDR, Service d'Endocrinologie, Diabète et Maladies Métaboliques, Laboratoire d'Hormonologie - Biochimie
- Study start
- Jan 2008
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 21 Mar 2014 (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.
Recently, concerns about the effect of atorvastatin intake on men fertility have been raised. However, this statin has never been investigated regarding its influence on male fertility, notably sperm quality.
The aim of this pilot study is to evaluate the efficacy and the safety of a decrease of cholesterol blood levels, induced by taking atorvastatin, on sperm quality of normocholesterolaemic and healthy men without confounding factors.
Detailed description
The main objective is to estimate the safety of atorvastatin on fertility of normocholesterolaemic and healthy men (having normal blood lipid profile and normal sperm parameters) by analyzing its effects on sperm parameters: ejaculate volume, sperm count, total and progressive motility, percentage of typical forms.
The secondary objectives are to assess the changes in:
- hormonal profile: gonadotropins and testosterone plasma levels
- lipid composition of sperm and seminal fluid;
- spermatozoa capacitation markers
- accessory glands markers.
The efficacy is estimated by measuring the lipid lowering action of atorvastatin. It is expected a decrease by 20 and 40% of total cholesterol blood and LDL-cholesterol levels, respectively (total cholesterol <1.5 g / l and LDL-cholesterol <1g / l).
Considering this protocol as a pilot study to evaluate safety and efficacy, sample size estimation was fixed considering a Fleming design at one stage. These designs with one group and multi-stages (between 1 and 5) can be seen as filtering steps leading to the decision type go/no go. With a type I error a and statistical power (1-β) equals respectively 5% and 90%, n=17 subjects were necessary to reject the hypotheses of minimal (p=0.85) and maximal (p=0.95) acceptable non-toxicity. If 1 subject or more presented a toxicity, the treatment was considered no safe. To measure the evolution of total cholesterol and LDL-cholesterol levels concerning the efficacy, n=17 subjects were necessary to show a minimal paired difference (to be detected) of 0.5 with expected standard-deviation of difference = 0.5, correlation coefficient of 0.5, a= 5% (two-sided) for a power greater than 90% (1-β=97%).
Subjects are included after a screening visit (visit 0), during which routine laboratory biochemical tests are performed, an electrocardiogram is taken, blood pressure, weight and height are measured; physical examination including testis evaluation and semen parameters are analyzed according to WHO standards 1999 .
The subjects take atorvastatin orally (10mg/day (d), Tahor©, Pfizer Laboratory) during 5 months allowing to study atorvastatin effects on human spermatogenesis and epididymal maturation (one cycle requiring approximately 3 months).
Blood and semen parameters were measured :
- before to take atorvastatin treatment (visit 1)
- at the end of the therapy (visit 3)
- and 3 months after the end of treatment, (visit 4) to perform measurements during different cycles of spermatogenesis on a same subject. After two months of treatment, a consultation (visit 2) is realized to ensure good tolerance to treatment and to control treatment efficiency.
Biochemical clinical and semen measurements take before treatment were considered as "control baseline measures".
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| atovastatin | Experimental | Drug: Atorvastatin |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Men :
- between 18 and 65 years ;
- with normal conventional semen parameters and negative semen culture according to WHO standards 1999 : volume ejaculate ≥ 2 ml, sperm count ≥ 20millions/ml, total motility ≥ 50% progressive motility ≥ 30%, typical forms ≥ 20%;
- with normal blood lipid profile: total cholesterol < 2.50g/L, triglycerides < 1.70g/L, HDL-C > 0.35 g/L and LDL-C < 2.2 g/L;
- without known pathology or ongoing treatment
Key exclusion criteria (7 listed)
- Subjects with medical or surgical history that may make them at risk during the study,
- Subjects with cons-indications to taking atorvastatin
- Subjects with an active liver disease or increased level of serum transaminases
- Subjects with a history of allergy
- Subjects whose lipid parameters do not match the inclusions criteria or receiving lipid-lowering therapy
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 |
|---|---|---|
| AtorvastatinAlso: cholesterol lowering drugThe aim of this pilot study is to evaluate the efficacy and the safety of a decrease of cholesterol blood levels, induced by taking atorvastatin, on sperm quality of normocholesterolaemic and healthy men without confounding factors. | Drug | atovastatin |
Primary outcome
Observations of all modifications on semen quality after 5 months of atorvastatin treatment
Time frame: at month 5
Observations of all modifications on semen quality after 5 months of atorvastatin treatment and after 3 months after its withdrawal
Time frame: at month 8
4 secondary outcomes
hormonal profile: gonadotropins and total testosterone plasma levels
Time frame: at month 5
lipid composition of sperm and seminal fluid
Time frame: at month 5
spermatozoa capacitation markers
Time frame: at month 5
accessory glands markers
Time frame: at month 5
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 21 Mar 2014.
- Derived from this study: PubMed 25016482Pons-Rejraji H, Brugnon F, Sion B, Maqdasy S, Gouby G, Pereira B, Marceau G, Gremeau AS, Drevet J, Grizard G, Janny L, Tauveron I. Evaluation of atorvastatin efficacy and toxicity on spermatozoa, accessory glands and gonadal hormones of healthy men: a pilot prospective clinical trial. Reprod Biol Endocrinol. 2014 Jul 12;12:65. doi: 10.1186/1477-7827-12-65.
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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.
Igor TAUVERON principal investigator
University Hospital, Clermont-Ferrand
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Atorvastatin in people with Healthy Volunteers and Normocholesterolaemic Men, run by University Hospital, Clermont-Ferrand 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 7 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 21 Mar 2014. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Observations of all modifications on semen quality after 5 months of atorvastatin treatment (time frame: at month 5). 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?
On the ClinicalTrials.gov record for NCT02094313, which also lists 1 linked publication.
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 21 Mar 2014.