Oxidative Stress Clinical Trial
Official title:
Diagnosis and Treatment of Male Infertility Related to Inflammatory Syndrome: Therapeutic Trial
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.
Progress of research. Timeframe Search
- Duration of inclusions: 30 months
- Duration of patient follow-up: 7 months
- Total duration of the study: 37 months Within the framework of their coverage in AMP,
the barren couples have a consultation with the doctors of the reproduction and one with
the biologists. Between these two visits, a spermatic balance assessment (EXAMINATION
N°0) is made including a semen culture, a spermogram or a test of migration survival
(TMS) and an elastase.
On the occasion of this examination, aliquots for the measure of 8OH-dG, fragmentation of the
spermatic DNA and seminal biochemistry will systematically be taken.
Within the framework of this standard balance assessment of infertility, it is possible that
an echography and a MRI of the genital ways are prescribed; if it is the case, the data of
these examinations will be collected in the case report form. But these examinations will not
be specifically asked for the search.
If a leukocytospermia ≥ 0,5*106/ml is discovered or an increase of the elastase ≥ 500 ng /
ml, the dosages of 8OH-dG, the fragmentation and the seminal biochemistry will be made.
The patients will then be seen in consultation of biology (CONSULTATION OF BIOLOGY N°0 =
visit of inclusion and randomization).
- If the patients present 8OH-dG > 35 %, and that their semen culture is negative, it will
be suggested to them being included in the protocol and the randomization will be made
that very day; the patients will receive or an anti-inflammatory treatment (Prednisone)
is a treatment placebo.
- If 8OH-dG < 35 % it will be suggested to them participating in the study of the
follow-up of the spontaneous evolution of the SO and of SI over 6 months.
A first complete balance assessment will be made in 1 month (EXAMINATION N°1) after the
beginning of the treatment in the study (Prednisone or placebo) so as to estimate the
evolution at the end of the treatment of the inflammatory and oxidative parameters This
balance assessment will not be realized at the inclusive but not randomized patient's.
Patients randomized in the study will have laboratory tests including:
- A semen analysis (leukocytospermia)
- A measure of oxidative stress (8OHd guanosine assay - assay of protein carbonyl - DNA
fragmentation)
- A seminal biochemistry (acid 1-4)alpha phosphatase, citrate, zinc, fructose, carnitine
and glucosidase
A second balance assessment will be asked 6 months (EXAMINATION N°2) after the beginning of
the treatment for two reasons: the first reason is that the improvement of the spermatic
parameters is slowly made. If a spermatic change settled down during years she is not going
to disappear in the fortnight. It is effectively the experience which we have of it.
Besides the spermatogenesis continuing over three months, a new cycle of production of sperm
cells can be estimated only more than three months after the treatment. The second reason is
that the second offenses of the chronic inflammations of the reproductive organ are extremely
frequent and it is to estimate this rate of second offense that the balance assessment will
be remotely asked for more by the treatment or in 6 months.
This review will include all tests of initial assessment:
- A semen analysis (leukocytospermia)
- A measure of oxidative stress (8OHd guanosine assay - assay of protein carbonyl - DNA
fragmentation)
- A seminal biochemistry (acid 1-4)alpha phosphatase, citrate, zinc, fructose, carnitine
and glucosidase
- An ultrasound of the genital tract and genital tract RMI without injection of any
compound
This visit will be scheduled for all patients, whether randomized or not. During this visit,
the results of tests carried out at 1 month and 6 months after initiation of treatment will
be analyzed. The investigator will collect adverse events that occurred since the
randomization visit.
Patients who during the examination in 6 months have a very significant improvement in their
semen parameters will propose cryopreserving their sperm.
Assays and analysis on the semen Collections of semen will be done in the Laboratory of
Reproductive Biology of each participating centre of research.
Most assays and analysis will be centralized at the Cochin Hospital. Measurement of elastase
Elastase assays will be centralized in the Laboratory of Reproductive Biology, Hospital
Cochin. The assays will be carried out from 150 µl total sperm collected after liquefaction
and frozen at -20 ° C.
Migration Survival Test (MST) This test will be done locally in each participating centre. A
smear slide will be made for a centralized analysis of the morphology, to avoid any "centre"
effects.
Seminal Biochemistry The biochemical seminal will be centralized in the Laboratory of
Biochemistry, Hospital Cochin. This assay, carried out on total sperm collected after
liquefaction, including assays of acid phosphatase, citrate, zinc, fructose, carnitine and
1-4.alpha Glucosidase The semen will be collected, centrifuged at 600g for 5 minutes. After
centrifugation, 500μl of the supernatant will be frozen at - 20 ° C and used for biochemical
seminal.
Measurement of oxidative stress The extent of oxidative stress will be centrally assessed in
Cochin Hospital. This assay, carried out on total sperm collected after liquefaction,
including the determination of 8OHd-Guanosine, the dosage of protein carbonyl and DNA
fragmentation.
The semen will be collected centrifuged at 600g for 5 minutes. After centrifugation:
- 250μl of the supernatant be frozen at - 20 ° C and used for determination of protein
carbonyl.
- The pellet will be used for the assay of 8OHdguanosine and DNA fragmentation.
Measurement of sperm motion parameters by CASA The measurement of sperm motion
parameters by CASA will be performed locally in each participating centre.
Ultrasound and MRI of the genital tract Ultrasounds and MRI will be performed in the genital
tract in the central radiology department of hospital Necker.
Conservation of the remaining sample of semen For patients with very significant improvement
in their semen parameters during the examination at 6 months, it will be offered
self-preservation of semen for any subsequent attempt of ART after the end of the study.
On the other hand, the remaining sample of semen, except if opposition from the patient, will
be kept after the end of the research for later use in future research on fertility and
inflammation. This collection will be kept at CECOS - Cochin Hospital, Bldg. Cassini - 27 rue
du FAUBOURG St Jacques, 75014 Paris under the supervision of Professor Jean-PHILIPPE Wolf.
Stopping rules Patients may discontinue their participation in research if they wish, at any
time and for whatever reason, or upon the decision of the investigator. However, the
treatment should not be stopped suddenly.
Stopping rules for the participation of a person seeking
- Poor adherence to protocol
- intercurrent disease between the inclusion visit and the visit at 1 month requiring
cessation of study. Following the study is that of surveillance.
Procedures for monitoring output test All output tests should be documented and the
investigator must specify the reason. For patients considered lost of sight, case report
forms should be filled to the last visit. The investigator will make every effort to contact
the patient and to know the reason for leaving the trial and his health.
Consequences Patients who quit from the trial will not be re-included in the study. Their
numbers are not effectively reused. These patients will still be followed in the
non-randomized part of the study.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT03255187 -
Effect of Dietary Supplemental Fish Oil in Alleviating Health Hazards Associated With Air Pollution
|
N/A | |
Completed |
NCT04136821 -
The Long-term Effects of Oceanix™ on Resistance Training Adaptations
|
N/A | |
Recruiting |
NCT03790345 -
Vitamin B6 and B12 in the Treatment of Movement Disorders Induced by Antipsychotics
|
Phase 2/Phase 3 | |
Completed |
NCT03358524 -
Effects of Vitamin E Supplementation on Free Radicals and Fat Level of Obese Adolescence in Jakarta, Indonesia
|
Phase 4 | |
Recruiting |
NCT05327348 -
Effectiveness of IV Vitamin C in Reducing Oxidative Stress Associated With Free Flap Surgery
|
Phase 3 | |
Completed |
NCT03288623 -
The Effects of Dark Chocolate Implementation in Elite Athletes
|
N/A | |
Completed |
NCT04419025 -
Efficacy of N-Acetylcysteine (NAC) in Preventing COVID-19 From Progressing to Severe Disease
|
Phase 2 | |
Completed |
NCT04597983 -
Effect of 8-week Intake of 2S-hesperidin on Performance, Body Composition and Biochemicals Markers in Amateur Cyclists
|
N/A | |
Not yet recruiting |
NCT06159543 -
The Effects of Fresh Mango Consumption on Cardiometabolic Outcomes in Free-living Individuals With Prediabetes
|
N/A | |
Enrolling by invitation |
NCT03030456 -
Whole Body Vibrations on Functional Capacity, Muscular Strength, and Biochemical Profile in Elders
|
N/A | |
Not yet recruiting |
NCT02202239 -
Effect of Induction and Maintenance of Anesthesia With Etomidate on Hemodynamics and Oxidative Stress in Diabetic Patients
|
Phase 4 | |
Completed |
NCT02256254 -
SIMOX - Induction of Oxidative Stress
|
Phase 2 | |
Recruiting |
NCT02048592 -
Impact of Immunonutrition on the Patients With Cystic Fibrosis
|
Phase 4 | |
Completed |
NCT01942460 -
Ferumoxytol for Iron-Deficiency Anemia in Chronic Kidney Disease and Peritoneal Dialysis Patients
|
Phase 4 | |
Completed |
NCT02463318 -
The Effect of Melatonin on Gene Expression and Activity of the Sirt1 and Its Target Genes Catalase and MnSOD in Multiple Sclerosis Patients and Healthy Subjects
|
N/A | |
Completed |
NCT01990391 -
Brazil Nut Consumption in Microvascular Endothelial Function, Oxidative Stress and Metabolic Abnormalities
|
N/A | |
Completed |
NCT02177383 -
Action of Essential Fatty Acids on the Expression of Antioxidant Genes and Athletic Performance
|
N/A | |
Completed |
NCT00845130 -
Quantitative in Vivo Biomarkers of Oxidative Stress in Diabetes
|
N/A | |
Completed |
NCT00607893 -
Efficacy of Continuous Positive Airway Pressure in Reducing Oxidative Stress in Individuals With Sleep Apnea
|
N/A | |
Active, not recruiting |
NCT00247507 -
The Effects of Acetylcysteine on Alleviating Damage of Oxidative Stress in Hemodialysis Patients
|
Phase 4 |