<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04414904</url>
  </required_header>
  <id_info>
    <org_study_id>20HH5998</org_study_id>
    <nct_id>NCT04414904</nct_id>
  </id_info>
  <brief_title>Determining the Reproductive Health of Men Post-COVID-19 Infection</brief_title>
  <official_title>Determining the Reproductive Health of Men Post-COVID-19 Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Imperial College London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Imperial College London</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Study rationale&#xD;
&#xD;
        1. An increasing proportion of the worldwide population is being infected with COVID-19.&#xD;
&#xD;
        2. There are ongoing and currently unanswered safety concerns about the effects of COVID-19&#xD;
           on reproductive health.&#xD;
&#xD;
        3. It will be immensely reassuring to rapidly report that COVID-19 has no detectable&#xD;
           effects on male endocrine or sperm function. Conversely, if COVID-19 does impair male&#xD;
           reproductive health, appropriate screening can be performed in couples trying to&#xD;
           conceive, and further research can be undertaken.&#xD;
&#xD;
        4. The proposed study will be simple, rapid, and authoritative for the UK and worldwide.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Male infertility results from impaired sperm function, and account for half of all&#xD;
      infertility. Fertility services have been reported to cost £325M annually in the UK(4) (REF).&#xD;
      Testosterone deficiency is one of the most common hormonal problems affecting men, leading to&#xD;
      osteoporosis, type 2 diabetes, obesity and depression(5).&#xD;
&#xD;
      Concerns have been raised about the potential effects of COVID-19 on male reproductive&#xD;
      dysfunction (male infertility and testosterone deficiency). A recent study has suggested that&#xD;
      COVID-19 may enter human cells by binding to receptors (special gates on cells that recognise&#xD;
      a specific molecule) for angiotensin converting enzyme 2 (ACE2)(6) . ACE2 receptors are found&#xD;
      at very high levels in the testes. Within the testes, ACE2 is found on developing sperm, the&#xD;
      'nurse cells' that help the sperm grow (Sertoli cells), and also on Leydig cells which are&#xD;
      needed to make the male sex hormone testosterone. In summary, this evidence suggests that&#xD;
      there is a plausible link why COVID-19 would cause male infertility and testosterone&#xD;
      deficiency.&#xD;
&#xD;
      All fertility treatment in the UK is regulated by the Human Fertility and Embryology&#xD;
      Authority (HFEA). The HFEA has prohibited on all non-cancer fertility treatment in the UK&#xD;
      between April 15th and May 12th 2020 due to the COVID-19 epidemic. It is important to rapidly&#xD;
      screen and report whether COVID-19 has any obvious effects in causing male infertility and&#xD;
      testosterone deficiency. It must be noted that a recent study(1) reported that COVID-19 is&#xD;
      not spread by human semen and therefore, semen processing should not risk staff to COVID-19&#xD;
      infection.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Unable to obtain approval&#xD;
  </why_stopped>
  <start_date type="Actual">June 10, 2020</start_date>
  <completion_date type="Actual">June 10, 2020</completion_date>
  <primary_completion_date type="Actual">June 10, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Semen parameters</measure>
    <time_frame>3 visits (up to 75 days apart)</time_frame>
    <description>Sperm concentration (x10^6/ml) between case and control group.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Sperm Parameters</measure>
    <time_frame>3 visits (up to 75 days apart)</time_frame>
    <description>Sperm Motility (%) between case and control group.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Sperm Parameters</measure>
    <time_frame>3 visits (up to 75 days apart)</time_frame>
    <description>Sperm normal morphology (%) between case and control group.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hormones measurement</measure>
    <time_frame>3 visits (up to 75 days apart)</time_frame>
    <description>Testosterone (nmol/L) between case and control group.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hormones measurement</measure>
    <time_frame>3 visits (up to 75 days apart)</time_frame>
    <description>Follicle Stimulating Hormone(IU/L) between case and control group.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hormones measurement</measure>
    <time_frame>3 visits (up to 75 days apart)</time_frame>
    <description>Luteinising hormone(IU/L) between case and control group.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Seminal Reactive oxygen species</measure>
    <time_frame>3 visits (up to 75 days apart)</time_frame>
    <description>Compare seminal reactive oxidative species (RLU/second/10^6sperm) between case and control group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sperm DNA fragmentation rate</measure>
    <time_frame>3 visits (up to 75 days apart)</time_frame>
    <description>Compare Sperm DNA fragmentation rate (%) between case and control group.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">0</enrollment>
  <condition>Infertility, Male</condition>
  <condition>Testosterone Deficiency</condition>
  <arm_group>
    <arm_group_label>Case group</arm_group_label>
    <description>Men 18-50 years of age&#xD;
Already attending hospital for another reason&#xD;
High risk of prior COVID-19 infection:&#xD;
EITHER Prior positive COVID-19 PCR test result&#xD;
OR history suggestive of COVID-19 illness</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <description>Men 18-50 years of age&#xD;
Already attending hospital for another reason&#xD;
Low risk of prior COVID-19 infection:&#xD;
EITHER Negative positive COVID-19 PCR test result within last 4 weeks&#xD;
OR no history suggestive of COVID-19 illness</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Exposure: Covid-19 infection</intervention_name>
    <description>Previous history of COVID-19 infection.</description>
    <arm_group_label>Case group</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Sperm DNA fragmentation testing only. No sequencing of human genomic DNA will take place.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        We will be recruiting participants by the following means:&#xD;
&#xD;
          1. Posters within Imperial College NHS Healthcare trust&#xD;
&#xD;
          2. Advertisements within newspapers&#xD;
&#xD;
          3. Online advertisements including in social media websites&#xD;
&#xD;
          4. Databases held by Imperial College NHS Healthcare trust whereby men have expressed an&#xD;
             interest to participate in future research&#xD;
&#xD;
          5. Patients attending the Andrology Department and other reproductive outpatient clinics&#xD;
             at Imperial College NHS healthcare trust&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men 18-50 years of age&#xD;
&#xD;
          -  Already attending hospital for another reason&#xD;
&#xD;
          -  Low risk of prior COVID-19 infection(EITHER Negative positive COVID-19 PCR test result&#xD;
             within last 4 weeks OR no history suggestive of COVID-19 illness)&#xD;
&#xD;
          -  High risk of prior COVID-19 infection(EITHER Prior positive COVID-19 PCR test result&#xD;
             OR history suggestive of COVID-19 illness)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Men with current symptoms of COVID-19 infection&#xD;
&#xD;
          -  Men currently self-isolating as per UK government advice for COVID-19 infection&#xD;
&#xD;
          -  Needle-phobia&#xD;
&#xD;
          -  Impaired ability to provide full consent to take part in the study&#xD;
&#xD;
          -  History of co-morbidity likely to affect male reproductive function e.g. undescended&#xD;
             testes, removal of testes, testicular cancer, drugs such as corticosteroids or&#xD;
             testosterone therapy.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Male</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
  </eligibility>
  <location>
    <facility>
      <name>Channa Jayasena</name>
      <address>
        <city>London</city>
        <state>Outside U.S./Canada</state>
        <zip>W12 0HS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>http://www.hfea.gov.uk</url>
    <description>The state of the fertility sector 2017-2018</description>
  </link>
  <link>
    <url>http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164916/</url>
    <description>Reference 1</description>
  </link>
  <reference>
    <citation>Wang Z, Xu X. scRNA-seq Profiling of Human Testes Reveals the Presence of the ACE2 Receptor, A Target for SARS-CoV-2 Infection in Spermatogonia, Leydig and Sertoli Cells. Cells. 2020 Apr 9;9(4):920. doi: 10.3390/cells9040920.</citation>
    <PMID>32283711</PMID>
  </reference>
  <reference>
    <citation>Wang S, Zhou X, Zhang T, Wang Z. The need for urogenital tract monitoring in COVID-19. Nat Rev Urol. 2020 Jun;17(6):314-315. doi: 10.1038/s41585-020-0319-7.</citation>
    <PMID>32313110</PMID>
  </reference>
  <reference>
    <citation>Hackett G, Kirby M, Edwards D, Jones TH, Rees J, Muneer A. UK policy statements on testosterone deficiency. Int J Clin Pract. 2017 Mar;71(3-4):e12901. doi: 10.1111/ijcp.12901. Epub 2017 Mar 20.</citation>
    <PMID>28318076</PMID>
  </reference>
  <reference>
    <citation>Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu N, Bi Y, Ma X, Zhan F, Wang L, Hu T, Zhou H, Hu Z, Zhou W, Zhao L, Chen J, Meng Y, Wang J, Lin Y, Yuan J, Xie Z, Ma J, Liu WJ, Wang D, Xu W, Holmes EC, Gao GF, Wu G, Chen W, Shi W, Tan W. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020 Feb 22;395(10224):565-574. doi: 10.1016/S0140-6736(20)30251-8. Epub 2020 Jan 30.</citation>
    <PMID>32007145</PMID>
  </reference>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>May 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>November 20, 2020</last_update_submitted>
  <last_update_submitted_qc>November 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 24, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>infertility</keyword>
  <keyword>hypogonadism</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infertility</mesh_term>
    <mesh_term>Infertility, Male</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04414904
org study id: 20HH5998
nct id: NCT04414904
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Study rationale

        1. An increasing proportion of the worldwide population is being infected with COVID-19.

        2. There are ongoing and currently unanswered safety concerns about the effects of COVID-19
           on reproductive health.

        3. It will be immensely reassuring to rapidly report that COVID-19 has no detectable
           effects on male endocrine or sperm function. Conversely, if COVID-19 does impair male
           reproductive health, appropriate screening can be performed in couples trying to
           conceive, and further research can be undertaken.

        4. The proposed study will be simple, rapid, and authoritative for the UK and worldwide.
Male infertility results from impaired sperm function, and account for half of all
      infertility. Fertility services have been reported to cost £325M annually in the UK(4) (REF).
      Testosterone deficiency is one of the most common hormonal problems affecting men, leading to
      osteoporosis, type 2 diabetes, obesity and depression(5).

      Concerns have been raised about the potential effects of COVID-19 on male reproductive
      dysfunction (male infertility and testosterone deficiency). A recent study has suggested that
      COVID-19 may enter human cells by binding to receptors (special gates on cells that recognise
      a specific molecule) for angiotensin converting enzyme 2 (ACE2)(6) . ACE2 receptors are found
      at very high levels in the testes. Within the testes, ACE2 is found on developing sperm, the
      'nurse cells' that help the sperm grow (Sertoli cells), and also on Leydig cells which are
      needed to make the male sex hormone testosterone. In summary, this evidence suggests that
      there is a plausible link why COVID-19 would cause male infertility and testosterone
      deficiency.

      All fertility treatment in the UK is regulated by the Human Fertility and Embryology
      Authority (HFEA). The HFEA has prohibited on all non-cancer fertility treatment in the UK
      between April 15th and May 12th 2020 due to the COVID-19 epidemic. It is important to rapidly
      screen and report whether COVID-19 has any obvious effects in causing male infertility and
      testosterone deficiency. It must be noted that a recent study(1) reported that COVID-19 is
      not spread by human semen and therefore, semen processing should not risk staff to COVID-19
      infection.
observational model: Case-Control
time perspective: Prospective
measure: Semen parameters
time frame: 3 visits (up to 75 days apart)
description: Sperm concentration (x10^6/ml) between case and control group.
measure: Sperm Parameters
time frame: 3 visits (up to 75 days apart)
description: Sperm Motility (%) between case and control group.
measure: Sperm Parameters
time frame: 3 visits (up to 75 days apart)
description: Sperm normal morphology (%) between case and control group.
measure: Hormones measurement
time frame: 3 visits (up to 75 days apart)
description: Testosterone (nmol/L) between case and control group.
measure: Hormones measurement
time frame: 3 visits (up to 75 days apart)
description: Follicle Stimulating Hormone(IU/L) between case and control group.
measure: Hormones measurement
time frame: 3 visits (up to 75 days apart)
description: Luteinising hormone(IU/L) between case and control group.
measure: Seminal Reactive oxygen species
time frame: 3 visits (up to 75 days apart)
description: Compare seminal reactive oxidative species (RLU/second/10^6sperm) between case and control group.
measure: Sperm DNA fragmentation rate
time frame: 3 visits (up to 75 days apart)
description: Compare Sperm DNA fragmentation rate (%) between case and control group.
arm group label: Case group
description: Men 18-50 years of age
Already attending hospital for another reason
High risk of prior COVID-19 infection:
EITHER Prior positive COVID-19 PCR test result
OR history suggestive of COVID-19 illness
arm group label: Control Group
description: Men 18-50 years of age
Already attending hospital for another reason
Low risk of prior COVID-19 infection:
EITHER Negative positive COVID-19 PCR test result within last 4 weeks
OR no history suggestive of COVID-19 illness
intervention type: Other
intervention name: Exposure: Covid-19 infection
description: Previous history of COVID-19 infection.
arm group label: Case group
Sperm DNA fragmentation testing only. No sequencing of human genomic DNA will take place.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Male
gender based: Yes
gender description: Male
minimum age: 18 Years
maximum age: 50 Years
facility: 
country: United Kingdom
url: http://www.hfea.gov.uk
description: The state of the fertility sector 2017-2018
url: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164916/
description: Reference 1
citation: Wang Z, Xu X. scRNA-seq Profiling of Human Testes Reveals the Presence of the ACE2 Receptor, A Target for SARS-CoV-2 Infection in Spermatogonia, Leydig and Sertoli Cells. Cells. 2020 Apr 9;9(4):920. doi: 10.3390/cells9040920.
PMID: 32283711
citation: Wang S, Zhou X, Zhang T, Wang Z. The need for urogenital tract monitoring in COVID-19. Nat Rev Urol. 2020 Jun;17(6):314-315. doi: 10.1038/s41585-020-0319-7.
PMID: 32313110
citation: Hackett G, Kirby M, Edwards D, Jones TH, Rees J, Muneer A. UK policy statements on testosterone deficiency. Int J Clin Pract. 2017 Mar;71(3-4):e12901. doi: 10.1111/ijcp.12901. Epub 2017 Mar 20.
PMID: 28318076
citation: Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu N, Bi Y, Ma X, Zhan F, Wang L, Hu T, Zhou H, Hu Z, Zhou W, Zhao L, Chen J, Meng Y, Wang J, Lin Y, Yuan J, Xie Z, Ma J, Liu WJ, Wang D, Xu W, Holmes EC, Gao GF, Wu G, Chen W, Shi W, Tan W. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020 Feb 22;395(10224):565-574. doi: 10.1016/S0140-6736(20)30251-8. Epub 2020 Jan 30.
PMID: 32007145
responsible party type: Sponsor
mesh term: Infertility
mesh term: Infertility, Male
sharing ipd: No