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Male InfertilityPhase 3NCT02605070

Pilot Study on the Effects of FSH Treatment on the Epigenetic Characteristics of Spermatozoa in Infertile Patients With Severe Oligozoospermia

A Phase 3 study testing Bravelle in people with Male Infertility, run by Instituto de Investigacion Sanitaria La Fe at 1 site in Spain.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Single center, prospective, open clinical study to determine the genomic imprint (epigenetic modification) in a series of male infertility patients with alterations in their spermiogram (oligozoospermia) compared to a group of fertile patients in order to evaluate the effect of FSH ( follicle stimulating hormone)… Read more about this study

Who is it for?
Ages 25 to 45 years, men onlyHealthy volunteers can take part
Conditions the study is for
Male Infertility
What is being tested?
Bravelle
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteSpain
Study dates
Nov 2015to 13 Jun 2017
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 25 to 45 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

None listed.

Who cannot join

  • Total sperm concentration <1 million.
  • Sperm motility of 0%.
  • History of cryptorchidism, malignant or benign tumors, known chromosomal abnormalities, testicular tor- sion, testicular trauma, orchitis.
  • Drug use in the past 120 days. thyroid dysfunction
  • Medical history:thyroid dysfunction, blood disease, diabetes.
  • Use of anabolic steroids in the past 2 years or for more than 2 years.
  • Body mass index >30 kg/m .
  • Intake of over 21 units of alcohol/week in the past 120 days.

Trial locations and contacts

1 site in 1 country.

Spain1 site

  • Hospital Universitari i Politècnic La Fe

    Valencia, 46026

Other trials in Spain

About this study

Single center, prospective, open clinical study to determine the genomic imprint (epigenetic modification) in a series of male infertility patients with alterations in their spermiogram (oligozoospermia) compared to a group of fertile patients in order to evaluate the effect of FSH ( follicle stimulating hormone) administration on these modifications and on male infertility.

Read the detailed description

Single center, prospective, open clinical study to determine the genomic imprint (epigenetic modification) in a series of male infertility patients with alterations in their spermiogram (oligozoospermia) compared to a group of fertile patients in order to evaluate the effect of FSH ( follicle stimulating hormone) administration on these modifications and on male infertility.

Main objective: To determine the genomic imprint (epigenetic modification) in a series of male infertility patients with alterations in their spermiogram (oligozoospermia) compared to a group of fertile patients in order to evaluate the effect of FSH administration on these modifications and on male infertility.

Secondary objectives

  • To assess the main characteristics of the spermiograms of infertility patients before and after FSH treatment.
  • To assess modifications in the hormones involved in sperm formation in infertility patients before and after treatment.
  • To analyze the results of assisted reproduction treatments in patients receiving FSH treatment.
Being tested
Bravelle
Medical subject headings
Infertility, Male

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BravelleDrug

    Bravelle will be provided to all patients in the treatment group by the principal investigator (PI) or another member of the research team.

    From week nine on, the patients will undergo a physical examination on three different occasions to assess the appearance of any adverse reactions during treatment. It will be up to the patient to communicate the appearance of signs or symptoms which could be associated with the use of the drug.

    At week 12 the patient will be scheduled for another visit to perform a semen study and to measure new hormone levels. To this end, a blood test will be carried out (FSH, LH, estradiol, total testosterone, SHBG, and albumin to calculate the amount of bioavailable testosterone). A semen sample will also be obtained to carry out a spermiogram according to WHO guidelines; part of this sample will be used for epigenetic analysis.

Study groups in NCT02605070
Study groupRoleWhat they receive
Infertility groupExperimentalPatients referred will be evaluated to participate in the study and then asked to take part.In this visit,the normal protocol for infertility patients will be followed and at least 2 spermiograms and a blood test analyzing the following parameters:FSH, LH,Estradiol,Total testosterone,SHBG, Albumin,Calculation of bioavailable testosterone,Prolactin.If these tests have not been performed,a second baseline visit will be scheduled.Should the patient meet all the inclusion criteria and after the patient has signed an informed consent form agreeing to participate in the study,the physician will prescribe the medication and schedule visits.Before initiating the treatment, they will provide a semen sample.This sample will be sent to the Center for Reproductive Biology,where the sample will be subjected to epigenetic analysis.The patient will be given samples of Bravelle.It is administered subcutaneously.The dose will be 150 IU 3times a week for 3months
Receives: Drug: Bravelle
Fertily groupNo interventionPatients who volunteer will be informed of the nature of the study and asked to sign the informed consent form. At least two spermiograms will be performed along with a blood test analyzing the following parameters:FSH,LH,Estradiol,Total testosterone,SHBG,Albumin,Estimation of bioavailable testosterone,Prolactin. A second baseline visit will be scheduled to evaluate the test results and to check whether these subjects meet all the inclusion criteria for the control group. Those subjects will provide a semen sample which will be stored at -20º C. Outpatient visit: week twelve: a physical exam will be carried out to identify any adverse reactions. A blood test and a semen sample will also be obtained.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Epigenetic modification

    To determine the genomic imprint (epigenetic modification) in a series of male infertility patients with alterations in their spermiogram (oligozoospermia) compared to a group of fertile patients in order to evaluate the effect of FSH administration on these modifications and on male infertility

    Measured: 12 weeks after treatment.

Secondary outcomes (3)

  1. To assess the main characteristics of the spermiograms of infertility patients before and after FSH treatment.

    To assess the main characteristics of the spermiograms of infertility patients before and after FSH treatment.

    Measured: First week and end of treatment visit (12 weeks).

  2. To assess modifications in the hormones involved in sperm formation in infertility patients before and after treatment.

    To assess modifications in the hormones involved in sperm formation in infertility patients before and after treatment.

    Measured: First week and end of treatment visit (12 weeks)

  3. Pregnancy rate.

    To analyze the results of assisted reproduction treatments in patients receiving FSH treatment.

    Measured: 6-7 weeks after transfer of the embryo.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Nov 2015 (estimated)
  2. Study startNov 2015
  3. Primary completion13 Jun 2017
  4. Study completion13 Jun 2017

Why it stopped: UNDER RECRUITMENT

Resources

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02605070
Sponsor's protocol ID
FSH_IMEN
Status last verified
May 2017
First submitted
9 Nov 2015
Last updated
2 Mar 2018
Results posted
No
Data monitoring committee
No

Publications

  • Boivin J, Bunting L, Collins JA, Nygren KG. International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care. Hum Reprod. 2007 Jun;22(6):1506-12. doi: 10.1093/humrep/dem046. Epub 2007 Mar 21.

    PubMed 17376819

  • Dohle GR, Halley DJ, Van Hemel JO, van den Ouwel AM, Pieters MH, Weber RF, Govaerts LC. Genetic risk factors in infertile men with severe oligozoospermia and azoospermia. Hum Reprod. 2002 Jan;17(1):13-6. doi: 10.1093/humrep/17.1.13.

    PubMed 11756355

  • Simoni M, Gromoll J, Dworniczak B, Rolf C, Abshagen K, Kamischke A, Carani C, Meschede D, Behre HM, Horst J, Nieschlag E. Screening for deletions of the Y chromosome involving the DAZ (Deleted in AZoospermia) gene in azoospermia and severe oligozoospermia. Fertil Steril. 1997 Mar;67(3):542-7. doi: 10.1016/s0015-0282(97)80083-0.

    PubMed 9091344

  • Gianotten J, Lombardi MP, Zwinderman AH, Lilford RJ, van der Veen F. Idiopathic impaired spermatogenesis: genetic epidemiology is unlikely to provide a short-cut to better understanding. Hum Reprod Update. 2004 Nov-Dec;10(6):533-9. doi: 10.1093/humupd/dmh045. Epub 2004 Oct 1.

    PubMed 15465836

  • Jenkins TG, Carrell DT. Dynamic alterations in the paternal epigenetic landscape following fertilization. Front Genet. 2012 Jul 31;3:143. doi: 10.3389/fgene.2012.00143. eCollection 2012.

    PubMed 23024648

  • Kelly TL, Li E, Trasler JM. 5-aza-2'-deoxycytidine induces alterations in murine spermatogenesis and pregnancy outcome. J Androl. 2003 Nov-Dec;24(6):822-30. doi: 10.1002/j.1939-4640.2003.tb03133.x.

    PubMed 14581508

  • Houshdaran S, Cortessis VK, Siegmund K, Yang A, Laird PW, Sokol RZ. Widespread epigenetic abnormalities suggest a broad DNA methylation erasure defect in abnormal human sperm. PLoS One. 2007 Dec 12;2(12):e1289. doi: 10.1371/journal.pone.0001289.

    PubMed 18074014

  • Kobayashi H, Sato A, Otsu E, Hiura H, Tomatsu C, Utsunomiya T, Sasaki H, Yaegashi N, Arima T. Aberrant DNA methylation of imprinted loci in sperm from oligospermic patients. Hum Mol Genet. 2007 Nov 1;16(21):2542-51. doi: 10.1093/hmg/ddm187. Epub 2007 Jul 17.

    PubMed 17636251

  • Benchaib M, Braun V, Ressnikof D, Lornage J, Durand P, Niveleau A, Guerin JF. Influence of global sperm DNA methylation on IVF results. Hum Reprod. 2005 Mar;20(3):768-73. doi: 10.1093/humrep/deh684. Epub 2005 Jan 7.

    PubMed 15640258

  • Reyes-Fuentes A, Chavarria ME, Carrera A, Aguilera G, Rosado A, Samojlik E, Iranmanesh A, Veldhuis JD. Alterations in pulsatile luteinizing hormone and follicle-stimulating hormone secretion in idiopathic oligoasthenospermic men: assessment by deconvolution analysis--a clinical research center study. J Clin Endocrinol Metab. 1996 Feb;81(2):524-9. doi: 10.1210/jcem.81.2.8636262.

    PubMed 8636262

  • Fujisawa M, Kanzaki M, Hayashi A, Tanaka H, Okada H, Arakawa S, Kamidono S. Alteration of the hypothalamus-pituitary-testis axis in oligozoospermic men with normal gonadotropin levels. Int J Urol. 1995 Sep;2(4):273-6. doi: 10.1111/j.1442-2042.1995.tb00471.x.

    PubMed 8564748

  • Boissonnas CC, Jouannet P, Jammes H. Epigenetic disorders and male subfertility. Fertil Steril. 2013 Mar 1;99(3):624-31. doi: 10.1016/j.fertnstert.2013.01.124.

    PubMed 23714437

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Bravelle in people with Male Infertility, run by Instituto de Investigacion Sanitaria La Fe at 1 site in Spain.

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 0 inclusion and 8 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: stopped early, as of the sponsor's last update on 2 Mar 2018. 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 Spain. 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 stopped early (reason given: UNDER RECRUITMENT). Results are not available in the source record.

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?

Epigenetic modification (time frame: 12 weeks after treatment.). 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 NCT02605070, which also lists 12 linked publications.

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 2 Mar 2018.

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