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Administration of Antioxidants to Infertile Men and Sperm Quality

Primary Purpose

Male Infertility

Status
Unknown status
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Spermotrend
Sponsored by
Aristotle University Of Thessaloniki
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Male Infertility focused on measuring sperm, infertility, asthenospermia, oligospermia, teratozoospermia, antioxidants

Eligibility Criteria

18 Years - 50 Years (Adult)MaleDoes not accept healthy volunteers

Inclusion criteria

  1. Men, 18-50 years old
  2. Infertility defined as follows:

    • Failure to obtain a pregnancy after at least twelve (12) months of regular sexual intercourse without the use of contraceptives or six (6) months if the woman is> 35 years old AND
    • At least one previous abnormal spermiogram, with at least one pathological parameter (concentration, motility, morphology), according to the WHO 2010 criteria.
  3. No treatment for infertility in the last three (3) months
  4. Normal hormone profile (TSH, FSH, LH, total testosterone, prolactin)
  5. Negative culture for mycoplasma or ureaplasma
  6. Physiological scrotal ultrasound

Exclusion criteria

  1. Genetic cause of infertility
  2. History of cryptorchidism
  3. History of orchectomy
  4. History of testicular cancer
  5. History of severe heart, liver or kidney disease
  6. History of endocrine disease (primary or secondary hypogonadism, hyperprolactinemia, thyroid, pituitary or adrenal disease)
  7. History of systemic disease or treatment in the last three (3) months
  8. BMI > 30 kg/m2
  9. Participation in another study and the possibility of the patient not being available for follow-up

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Intervention Group

    Control Group

    Arm Description

    Outcomes

    Primary Outcome Measures

    Sperm parameters
    Sperm motility(Sperm motility was classified using a four-category scheme: A:rapid progressive, B:slow progressive, C:non-progressive, and D:immotile , %A+B, normal values >32% A+B)
    Sperm parameters
    Sperm motility(Sperm motility was classified using a four-category scheme: A:rapid progressive, B:slow progressive, C:non-progressive, and D:immotile , %A+B, normal values >32% A+B)
    Sperm parameters
    Sperm concentration (ml, normal values > 1.5 ml)
    Sperm parameters
    Sperm concentration (ml, normal values > 1.5 ml)
    Sperm parameters
    Sperm vitality (%, normal values > 58%)
    Sperm parameters
    Sperm vitality (%, normal values > 58%)
    Sperm parameters
    Sperm morphology(Tygerberg Strict Criteria were used for the evaluation of human sperm morphology, normal form per 100 sperm, normal values >4%)
    Sperm parameters
    Sperm morphology(Tygerberg Strict Criteria were used for the evaluation of human sperm morphology, normal form per 100 sperm, normal values >4%)

    Secondary Outcome Measures

    Reactive Oxygen Species (ROS)
    ROS (8-hydroxy-2-deoxy-quanosine%, normal values < 3% on sperm)
    Reactive Oxygen Species (ROS)
    ROS (8-hydroxy-2-deoxy-quanosine%, normal values < 3% on sperm)
    DNA fragmentation Index (DFI)
    DFI (%DFI: % sperm cells containing damaged DNA)
    DNA fragmentation Index (DFI)
    DFI (%DFI: % sperm cells containing damaged DNA)

    Full Information

    First Posted
    December 19, 2019
    Last Updated
    March 27, 2020
    Sponsor
    Aristotle University Of Thessaloniki
    Collaborators
    Andrology lab Zeginiadou, Armatura
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04256278
    Brief Title
    Administration of Antioxidants to Infertile Men and Sperm Quality
    Official Title
    Does Antioxidant Administration Improve Sperm Quality in Infertile Men
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2020
    Overall Recruitment Status
    Unknown status
    Study Start Date
    March 30, 2020 (Anticipated)
    Primary Completion Date
    January 30, 2021 (Anticipated)
    Study Completion Date
    December 30, 2022 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Aristotle University Of Thessaloniki
    Collaborators
    Andrology lab Zeginiadou, Armatura

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The purpose of this randomized clinical trial is to assess the effect of oral antioxidant administration to infertile men, by evaluating semen variables, sperm DFI and levels of ROS. Oral antioxidants or placebo will be given for 3 consecutive months. The study will recruit infertile men, who have one previous abnormal spermiogram, with at least one pathological variable (concentration, motility, morphology), according to WHO 2010 criteria. Participants will be recruited in the outpatient clinic of the Unit of Human Reproduction and of the Unit of Reproductive Endocrinology at the 1st Ob/Gyn Dept.
    Detailed Description
    Infertility affects up to 15% of couples trying to conceive with the male factor contributing in about 50% of cases. Oxidative stress (OS) has been found as one of the many factors causing male infertility, by inducing sperm damage. OS causes cell damage due to the raised production of reactive oxygen species (ROS), that overcome the antioxidant mechanisms of the human body. ROS are oxidizing agents that are produced as a by-product of oxygen metabolism, having at least one free electron. Due to this free electrone in their outer layer, the form very active or unstable substances. While small amounts of ROS are necessary for the proper function of sperm, increased amounts have a negative effect on sperm quality and can harm its fertility potential, thus inducing male infertility. Spermatozoa were the first cells found to be sensitive to OS, as they lack the necessary repair cytoplasmic enzyme systems, thus being unable to repair damage. In addition, their cytoplasmic membranes are rich in polyunsaturated fatty acids (PUFAs), making them highly susceptible to oxygen-induced damage, such as lipid peroxidation (LPO). Rapid loss of intracellular adenosine triphosphate (ATP) by LPO, is responsible for axial damage, morphological damage to the sperm neck and reduced sperm motility; these events contribute to reduced sperm motility. OS has also been associated with reduced fertilization, delayed intrauterine growth, miscarriages, birth defects (including autism) and childhood cancer. ROS found in semen come from a variety of endogenous and exogenous factors. Human sperm includes mature and immature sperm cells, leukocytes, and white blood cells. The leukocytes (mainly neutrophils and macrophages) and the immature spermatozoa are considered the major endogenous sources of ROS, whereas lifestyle, such as smoking, excessive alcohol consumption and other environmental factors such as radiation and toxins may contribute to the production of exogenous ROS. As oxidative stress (OS) results from the imbalance of ROS overproduction and the reduced capacity of sperm antioxidant systems, many studies have aimed to improve sperm quality by administering antioxidant therapeutic regimens. In general, antioxidant therapy involves the administration of oral antioxidants, and the in vitro addition of antioxidants to culture media that are used for sample preparation in assisted reproduction techniques (ART). Many different antioxidants combinations have been studied. More and more studies have shown the beneficial effect of antioxidants on reducing sperm fragmentation and improving sperm quality. Agarwal & Sekhon's study showed a positive correlation between antioxidant therapy and various semen parameters. However, no firm conclusion regarding the beneficial effect of oral antioxidants can be made, as the majority of available studies had small sample size, used different antioxidant combinations, and the techniques that were used for the detection of ROS and DNA fragmentation index (DFI) were not standardized. AIM OF THE STUDY The purpose of this randomized clinical trial is to assess the effect of oral antioxidant administration to infertile men, by evaluating semen variables, sperm DFI and levels of ROS.Oral antioxidants or placebo will be given for 3 consecutive months. This study will take place at the Unit of Reproductive Endocrinology at the 1st Ob/Gyn Dept, Medical School, Aristotle University of Thessaloniki in collaboration with the private andrology diagnostic center of Mr Th. Zeginiadou. PATIENTS The study will recruit infertile men, who have one previous abnormal spermiogram, with at least one pathological variable (concentration, motility, morphology), according to WHO 2010 criteria. OUTCOMES Main Outcome: WHO Sperm analysis variables: concentration, motility, morphology. Secondary outcomes: Concentration of ROS in sperm and sperm DFI STUDY DESIGN Type of study: Randomized clinical trial The study will recruit infertile men, who have one previous abnormal spermiogram, with at least one pathological variable (concentration, motility, morphology), according to WHO 2010 criteria. Participants will be recruited in the outpatient clinic of the Unit of Human Reproduction and of the Unit of Reproductive Endocrinology at the 1st Ob/Gyn Dept. Selected participants will sign the consent form and will be asked to sample sperm at the private andrology diagnostic center of Mr Th. Zeginiadou. The sperm samples will be evaluated regarding the concentration, motility, morphology and vitality of spermatozoa, as well as the concentration of ROS, and DFI. Oral antioxidants or placebo will be given for 3 consecutive months. At the end of the 3 months period participants will be asked to re-sample their sperm in order to evaluate the same variables. Sample size calculation Estimated sample size for two-sample means test, assuming and common standard deviation of 15 and a mean motility of 20 in the control group and 30 in the antioxidant group results in calculated sample size of 74. To allow for dropouts 80 patients will be recruited.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Male Infertility
    Keywords
    sperm, infertility, asthenospermia, oligospermia, teratozoospermia, antioxidants

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Model Description
    quadruple-blind study
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Masking Description
    use of placebo, masked randomization list
    Allocation
    Randomized
    Enrollment
    80 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Intervention Group
    Arm Type
    Experimental
    Arm Title
    Control Group
    Arm Type
    Placebo Comparator
    Intervention Type
    Other
    Intervention Name(s)
    Spermotrend
    Intervention Description
    oral administration of antioxidants for three months
    Primary Outcome Measure Information:
    Title
    Sperm parameters
    Description
    Sperm motility(Sperm motility was classified using a four-category scheme: A:rapid progressive, B:slow progressive, C:non-progressive, and D:immotile , %A+B, normal values >32% A+B)
    Time Frame
    immediately before treatment initiation
    Title
    Sperm parameters
    Description
    Sperm motility(Sperm motility was classified using a four-category scheme: A:rapid progressive, B:slow progressive, C:non-progressive, and D:immotile , %A+B, normal values >32% A+B)
    Time Frame
    immediately after the end of a 3 month treatment
    Title
    Sperm parameters
    Description
    Sperm concentration (ml, normal values > 1.5 ml)
    Time Frame
    immediately before treatment initiation
    Title
    Sperm parameters
    Description
    Sperm concentration (ml, normal values > 1.5 ml)
    Time Frame
    immediately after the end of a 3 month treatment
    Title
    Sperm parameters
    Description
    Sperm vitality (%, normal values > 58%)
    Time Frame
    immediately before treatment initiation
    Title
    Sperm parameters
    Description
    Sperm vitality (%, normal values > 58%)
    Time Frame
    immediately after the end of a 3 month treatment
    Title
    Sperm parameters
    Description
    Sperm morphology(Tygerberg Strict Criteria were used for the evaluation of human sperm morphology, normal form per 100 sperm, normal values >4%)
    Time Frame
    immediately before treatment initiation
    Title
    Sperm parameters
    Description
    Sperm morphology(Tygerberg Strict Criteria were used for the evaluation of human sperm morphology, normal form per 100 sperm, normal values >4%)
    Time Frame
    immediately after the end of a 3 month treatment
    Secondary Outcome Measure Information:
    Title
    Reactive Oxygen Species (ROS)
    Description
    ROS (8-hydroxy-2-deoxy-quanosine%, normal values < 3% on sperm)
    Time Frame
    immediately before treatment initiation
    Title
    Reactive Oxygen Species (ROS)
    Description
    ROS (8-hydroxy-2-deoxy-quanosine%, normal values < 3% on sperm)
    Time Frame
    immediately after the end of a 3 month treatment
    Title
    DNA fragmentation Index (DFI)
    Description
    DFI (%DFI: % sperm cells containing damaged DNA)
    Time Frame
    immediately before treatment initiation
    Title
    DNA fragmentation Index (DFI)
    Description
    DFI (%DFI: % sperm cells containing damaged DNA)
    Time Frame
    immediately after the end of a 3 month treatment

    10. Eligibility

    Sex
    Male
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    50 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion criteria Men, 18-50 years old Infertility defined as follows: Failure to obtain a pregnancy after at least twelve (12) months of regular sexual intercourse without the use of contraceptives or six (6) months if the woman is> 35 years old AND At least one previous abnormal spermiogram, with at least one pathological parameter (concentration, motility, morphology), according to the WHO 2010 criteria. No treatment for infertility in the last three (3) months Normal hormone profile (TSH, FSH, LH, total testosterone, prolactin) Negative culture for mycoplasma or ureaplasma Physiological scrotal ultrasound Exclusion criteria Genetic cause of infertility History of cryptorchidism History of orchectomy History of testicular cancer History of severe heart, liver or kidney disease History of endocrine disease (primary or secondary hypogonadism, hyperprolactinemia, thyroid, pituitary or adrenal disease) History of systemic disease or treatment in the last three (3) months BMI > 30 kg/m2 Participation in another study and the possibility of the patient not being available for follow-up
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Stratis Kolibianakis, Professor
    Phone
    2313323374
    Email
    stratis.kolibianakis@gmail.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Pinelopi Ioannidou, MD
    Phone
    6986707120
    Email
    pinioannidou@hotmail.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Stratis Kolibianakis, Professor
    Organizational Affiliation
    Aristotle University Thessaloniki
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    29713542
    Citation
    Majzoub A, Agarwal A. Systematic review of antioxidant types and doses in male infertility: Benefits on semen parameters, advanced sperm function, assisted reproduction and live-birth rate. Arab J Urol. 2018 Jan 2;16(1):113-124. doi: 10.1016/j.aju.2017.11.013. eCollection 2018 Mar.
    Results Reference
    result
    PubMed Identifier
    24872947
    Citation
    Agarwal A, Virk G, Ong C, du Plessis SS. Effect of oxidative stress on male reproduction. World J Mens Health. 2014 Apr;32(1):1-17. doi: 10.5534/wjmh.2014.32.1.1. Epub 2014 Apr 25.
    Results Reference
    result
    PubMed Identifier
    23543240
    Citation
    Chen SJ, Allam JP, Duan YG, Haidl G. Influence of reactive oxygen species on human sperm functions and fertilizing capacity including therapeutical approaches. Arch Gynecol Obstet. 2013 Jul;288(1):191-9. doi: 10.1007/s00404-013-2801-4. Epub 2013 Mar 30.
    Results Reference
    result
    PubMed Identifier
    18281241
    Citation
    Tremellen K. Oxidative stress and male infertility--a clinical perspective. Hum Reprod Update. 2008 May-Jun;14(3):243-58. doi: 10.1093/humupd/dmn004. Epub 2008 Feb 14.
    Results Reference
    result
    PubMed Identifier
    19768529
    Citation
    Zini A, San Gabriel M, Baazeem A. Antioxidants and sperm DNA damage: a clinical perspective. J Assist Reprod Genet. 2009 Aug;26(8):427-32. doi: 10.1007/s10815-009-9343-5. Epub 2009 Sep 19.
    Results Reference
    result

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