Male Infertility Related With Post Infection Inflammatory Syndrome (SIGMA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01407484
First received: June 30, 2011
Last updated: August 2, 2013
Last verified: July 2013
  Purpose

BACKGROUND: One couple out of 6 consults for infertility during their sexual life. In 60% of cases a male factor is associated or is the main infertility factor. Inflammatory Syndrome (IS), characterized by the presence of a leukocytospermia is found in 12% of the cases. Leukocyte degranulation causes oxidative stress (OS) through the formation of free radicals attacking the sperm cell functions.

HYPOTHESIS: To establish the responsibility of the IS, and OS, in chronicle inflammatory male infertility, the investigators hypothesize that its treatment (as well as its possible cause) must restore or improve the fertilizing capacity of patients sperm.

METHODS: This prospective randomized study will test the response to the treatment. The investigators shall measure cellular degradation products due to the OS, thereby certifying that it does have a deleterious effect on sperm cell. Seminal biochemistry will also assess the impact of the syndrome on the genital tract glands and follow its evolution.

The patients will be included in the study as soon as the leukocytospermia will be > 0,5*106/ml or as soon as the elastase will be > 500 ng/mL.

The examinations will be performed using flow cytometry, CASA (Computer Assisted Semen Analysis). The analysis of sperm morphology will be centralized.

Primary endpoint will be a reduction in the percentage of 8OH-dG below 35 %. We anticipate that it should arrive to 20 % of the patients included in the arm treatment by corticosteroid therapy. All in all will thus be needed 50 patients in the group placebo and 50 in the group treated.

Secondary endpoint the improvement of the spermatic parameters and the reduction of the fragmentation of the DNA of sperm cells to the treated subjects.

All these biological markers will be evaluated 6 month after the treatment:

  • Fragmentation of the spermatic DNA below 37 % during the follow-up in 6 months
  • Leukocytospermia and elastase
  • Seminal biochemistry
  • Other markers of the inflammatory syndrome and oxidative stress (protein carbonyl, 8OHd-Guanosine)
  • Possibly the radiological examinations (Ultrasound and MRI of the genital tract)

In addition it would allow us to propose a policy of prevention towards acquired post-infectious male infertility.


Condition Intervention
Male Infertility
Leukopenia
Postinfection Inflammation
Oxidative Stress
Drug: Prednisone
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Diagnosis and Treatment of Male Infertility Related to Inflammatory Syndrome: Therapeutic Trial

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • The number of live motile spermatozoa six month after the treatment [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Reduction of the percentage of the spermatic 8OH-dG under 35 % to 20 % of the patients between the visit of inclusion / randomization and the visit of follow-up in 6 months


Secondary Outcome Measures:
  • biological markers [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Several biological markers will be evaluated 6 months after the treatment, as markers of inflammation and oxidative stress (sperm DNA fragmentation, protein carbonyl, 8OHdGuanosine, leukocytospermia and elastase, seminal biochemistry,ultrasound, and MRI of the genital tract


Estimated Enrollment: 600
Study Start Date: March 2011
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
Cortancyl (prednisone) 0,2 mg/kg/day for 3 weeks and 0,1mg/kg/day for 1 week
Drug: Prednisone
0,2 mg/kg/day for 3 weeks and 0,1mg/kg/day for 1 week.
Other Name: Prednisone
Placebo Comparator: Placebo
Placebo
Drug: Placebo
Placebo 0,2 mg/kg/day for 3 weeks and 0,1mg/kg/day for 1 week
Other Name: Placebo

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria :

  • Man over 18 years old
  • Patient presenting a leukocytospermia ≥ 0,5*106 /ml or an elastase ≥ 500ng/ml
  • No infection
  • Signed informed consent

Exclusion criteria :

  • Patient having less of 106 /ml of sperm cells in the ejaculate
  • Patients with diabetes or receiving treatment for diabetes
  • Patients already taking anti-inflammatory drugs
  • Patients with ongoing anticoagulant therapy
  • Patients with history of allergy to anti-inflammatory drug
  • Patients with a history of peptic ulcers
  • Patient with history of cardiovascular disease (hypertension, cardiac arrhythmia, ...)
  • Patients with psychological disorders
  • Patient with an infectious condition except for specified indications of Prednisone
  • Patients with some evolutional viruses(including hepatitis, herpes, chickenpox, shingles)
  • Patient is in a psychotic state still not controlled by treatment
  • Patient receiving a live vaccine
  • Patients with hypersensitivity to any component of Prednisone
  • Patient not affiliated with a social security system

Criteria for randomization

- Patient meeting all inclusion criteria and none of exclusion, and having a 8OH desoxy Guanosine increased ≥ 35%.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01407484

Contacts
Contact: Jean-Philippe WOLF, MD, PhD 0033158411171 jean-philippe.wolf@cch.aphp.fr
Contact: Laurence Lecomte, PhD +331 58 41 35 45 laurence.lecomte@cch.aphp.fr

Locations
France
Cochin Hospital Recruiting
Paris, France, 75014
Principal Investigator: Jean-Philippe Wolf, MD, PhD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Jean-Philippe Wolf, MD, Phd AP-HP
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01407484     History of Changes
Other Study ID Numbers: P081215
Study First Received: June 30, 2011
Last Updated: August 2, 2013
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Infertility
Assisted reproductive technology
Double blind therapeutical trial
Multicentric study
Prospective randomized study

Additional relevant MeSH terms:
Infertility
Infertility, Male
Inflammation
Leukopenia
Genital Diseases, Male
Genital Diseases, Female
Pathologic Processes
Leukocyte Disorders
Hematologic Diseases
Prednisone
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on July 24, 2014