<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/NCT03829943</url>
  </required_header>
  <id_info>
    <org_study_id>MOD00002311</org_study_id>
    <nct_id>NCT03829943</nct_id>
  </id_info>
  <brief_title>Vitamin D and Human Sperm DNA Fragmentation</brief_title>
  <official_title>Effects of Vitamin D on Human Sperm DNA Fragmentation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sanford Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sanford Health</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study will be to investigate if there is a correlation between Vitamin D&#xD;
      levels and Sperm DNA Fragmentation. This is a prospective, cohort study. In this study male&#xD;
      participants presenting with their partners because of inability to conceive will be&#xD;
      recruited for this study. Participants will have a blood sample drawn which will be tested&#xD;
      for Vitamin D level. The investigators will then compare sperm DNA fragmentation between&#xD;
      normal Vitamin D levels, Vitamin D insufficiency, and Vitamin D deficiency. All infertile&#xD;
      males who present to the investigators' infertility clinic have a Semen analysis and Sperm&#xD;
      chromatin Structure Assay (SCSA). The research part of the study will be to obtain the&#xD;
      Vitamin D level.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Vitamin D plays an important role in bone metabolism and has also been discovered to&#xD;
      influence male reproduction. Vitamin D binds to the Vitamin D receptor which then can bind to&#xD;
      Vitamin D response elements in the DNA which can alter transcription. By changing&#xD;
      transcription it can have long term effects on cellular metabolism. Previous studies have&#xD;
      demonstrated abnormalities in sperm motility and morphology in males who are Vitamin D&#xD;
      deficient. The mechanism by which Vitamin D affects spermatogenesis (formation of sperm) is&#xD;
      unknown. One possibly mechanism by which deficient Vitamin D may affect sperm formation is&#xD;
      through DNA fragmentation. The head of the sperm contains all the DNA. When a sperm cell is&#xD;
      made the DNA in the nucleus must be super compacted to accomplish sperm formation. To&#xD;
      sufficiently compact the DNA, first the DNA is 'turned off' and then very tightly wound (or&#xD;
      compacted) into toroids (like small tires) which are stacked one on top of another. During&#xD;
      this process of compaction the DNA will occasionally break or fragment. The egg can repair&#xD;
      the DNA fragmentation as long as there is not a large amount of breakage. If the DNA&#xD;
      fragmentation exceeds a certain amount then fertilization and early development of the embryo&#xD;
      may be adversely affected. DNA fragmentation can be tested by using the Sperm Chromatin&#xD;
      Structure Assay (SCSA), which the investigators currently measure in males who present with&#xD;
      their partners with infertility. Previous studies have suggested that the abnormalities in&#xD;
      sperm due to vitamin D deficiency may be related to increased DNA fragmentation. This study&#xD;
      will assist in understanding the cause of sperm abnormalities in subjects with Vitamin D&#xD;
      deficiency.&#xD;
&#xD;
      This is a prospective, cohort study. In this study male patients who present with inability&#xD;
      to conceive will be asked to be involved in this study. After agreement with the study, a&#xD;
      blood sample drawn which will be tested for Vitamin D level. The investigators will then&#xD;
      compare sperm DNA fragmentation between normal Vitamin D levels, Vitamin D insufficiency, and&#xD;
      Vitamin D deficiency. All infertile males presenting to the investigators' infertility clinic&#xD;
      have a Semen analysis and Sperm chromatin Structure Assay (SCSA). The research part of the&#xD;
      study will be to obtain the Vitamin D level.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 21, 2019</start_date>
  <completion_date type="Anticipated">February 2022</completion_date>
  <primary_completion_date type="Anticipated">February 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Sperm DNA Fragmentation</measure>
    <time_frame>1 year</time_frame>
    <description>Human Sperm DNA fragmentation will be determined by the Sperm Chromatin Structure Assay.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>High DNA stainability</measure>
    <time_frame>1 year</time_frame>
    <description>High DNA stainability is determined by the Sperm Chromatin Structure Assay and is consistent with immature sperm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sperm density</measure>
    <time_frame>1 year</time_frame>
    <description>This will be determined by microscopic analysis of participant's semen and expressed as millions per milliliter</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Sperm motility</measure>
    <time_frame>1 year</time_frame>
    <description>This will be determined by microscopic analysis of participant's semen and expressed as percent motile.</description>
  </other_outcome>
  <other_outcome>
    <measure>Sperm morphology</measure>
    <time_frame>1 year</time_frame>
    <description>This will be determined by microscopic analysis of participant's semen and will be expressed as percent normal forms.</description>
  </other_outcome>
  <other_outcome>
    <measure>Height</measure>
    <time_frame>1 year</time_frame>
    <description>Measured by stadiometer and recorded in centimeters.</description>
  </other_outcome>
  <other_outcome>
    <measure>Weight</measure>
    <time_frame>1 year</time_frame>
    <description>Measured using digital, medical scale</description>
  </other_outcome>
  <other_outcome>
    <measure>BMI</measure>
    <time_frame>1 year</time_frame>
    <description>weight and height will be combined to report BMI in kg/m^2</description>
  </other_outcome>
  <other_outcome>
    <measure>Tobacco status</measure>
    <time_frame>1 year</time_frame>
    <description>Patient will be asked if uses tobacco products: smoke, smokeless</description>
  </other_outcome>
  <other_outcome>
    <measure>Race/ethnicity</measure>
    <time_frame>1 year</time_frame>
    <description>Patient will self identify race/ethnicity</description>
  </other_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">230</enrollment>
  <condition>Infertility,Male</condition>
  <condition>Vitamin D Deficiency</condition>
  <arm_group>
    <arm_group_label>Vitamin D deficiency</arm_group_label>
    <description>The study group will be males discovered to have Vitamin D deficiency.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <description>The control group will be males with normal Vitamin D status</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Vitamin D</intervention_name>
    <description>Blood will be drawn for Vitamin D level</description>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_label>Vitamin D deficiency</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Male partners of infertile couples. All males who present to our Infertility clinic will be&#xD;
        offered participation.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male with diagnosis of infertility.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Azoospermia&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>56 Years</maximum_age>
  </eligibility>
  <overall_contact>
    <last_name>Keith A Hansen, MD</last_name>
    <phone>6053288839</phone>
    <email>Keith.Hansen@SanfordHealth.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Angela Haldeman, RN</last_name>
    <phone>6053288800</phone>
    <email>Angela.Haldeman@SanfordHealth.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Sanford Health Fertility and Reproductive Medicine</name>
      <address>
        <city>Sioux Falls</city>
        <state>South Dakota</state>
        <zip>57105</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Keith Hansen, MD</last_name>
      <phone>605-328-8829</phone>
      <email>keith.hansen@sanfordhealth.org</email>
    </contact>
    <contact_backup>
      <last_name>Angela Haldeman, RN</last_name>
      <phone>605-328-8800</phone>
      <email>angela.haldeman@sanfordhealth.org</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Blomberg Jensen M, Bjerrum PJ, Jessen TE, Nielsen JE, Joensen UN, Olesen IA, Petersen JH, Juul A, Dissing S, Jorgensen N. Vitamin D is positively associated with sperm motility and increases intracellular calcium in human spermatozoa. Hum Reprod. 2011 Jun;26(6):1307-17. doi: 10.1093/humrep/der059. Epub 2011 Mar 22.</citation>
    <PMID>21427118</PMID>
  </reference>
  <reference>
    <citation>Bunde E, Hanssen K, Huntington MK. Vitamin D status in eastern South Dakota. S D Med. 2012 Jun;65(6):227, 229, 231.</citation>
    <PMID>22856011</PMID>
  </reference>
  <reference>
    <citation>Boisen IM, Bollehuus Hansen L, Mortensen LJ, Lanske B, Juul A, Blomberg Jensen M. Possible influence of vitamin D on male reproduction. J Steroid Biochem Mol Biol. 2017 Oct;173:215-222. doi: 10.1016/j.jsbmb.2016.09.023. Epub 2016 Sep 28.</citation>
    <PMID>27693423</PMID>
  </reference>
  <reference>
    <citation>Blomberg Jensen M, Lawaetz JG, Petersen JH, Juul A, Jorgensen N. Effects of Vitamin D Supplementation on Semen Quality, Reproductive Hormones, and Live Birth Rate: A Randomized Clinical Trial. J Clin Endocrinol Metab. 2018 Mar 1;103(3):870-881. doi: 10.1210/jc.2017-01656.</citation>
    <PMID>29126319</PMID>
  </reference>
  <reference>
    <citation>Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Guidelines for preventing and treating vitamin D deficiency and insufficiency revisited. J Clin Endocrinol Metab. 2012 Apr;97(4):1153-8. doi: 10.1210/jc.2011-2601. Epub 2012 Mar 22. No abstract available.</citation>
    <PMID>22442274</PMID>
  </reference>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>January 31, 2019</study_first_submitted>
  <study_first_submitted_qc>February 1, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>October 8, 2020</last_update_submitted>
  <last_update_submitted_qc>October 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sanford Health</investigator_affiliation>
    <investigator_full_name>Keith Hansen</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infertility</mesh_term>
    <mesh_term>Infertility, Male</mesh_term>
    <mesh_term>Vitamin D Deficiency</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin D</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Plan to share individual participant data (IPD) with researchers who desire information.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>The data will be available after collection complete and will remain available for 3 years.</ipd_time_frame>
    <ipd_access_criteria>Investigator.</ipd_access_criteria>
  </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/NCT03829943
org study id: MOD00002311
nct id: NCT03829943
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study will be to investigate if there is a correlation between Vitamin D
      levels and Sperm DNA Fragmentation. This is a prospective, cohort study. In this study male
      participants presenting with their partners because of inability to conceive will be
      recruited for this study. Participants will have a blood sample drawn which will be tested
      for Vitamin D level. The investigators will then compare sperm DNA fragmentation between
      normal Vitamin D levels, Vitamin D insufficiency, and Vitamin D deficiency. All infertile
      males who present to the investigators' infertility clinic have a Semen analysis and Sperm
      chromatin Structure Assay (SCSA). The research part of the study will be to obtain the
      Vitamin D level.
Vitamin D plays an important role in bone metabolism and has also been discovered to
      influence male reproduction. Vitamin D binds to the Vitamin D receptor which then can bind to
      Vitamin D response elements in the DNA which can alter transcription. By changing
      transcription it can have long term effects on cellular metabolism. Previous studies have
      demonstrated abnormalities in sperm motility and morphology in males who are Vitamin D
      deficient. The mechanism by which Vitamin D affects spermatogenesis (formation of sperm) is
      unknown. One possibly mechanism by which deficient Vitamin D may affect sperm formation is
      through DNA fragmentation. The head of the sperm contains all the DNA. When a sperm cell is
      made the DNA in the nucleus must be super compacted to accomplish sperm formation. To
      sufficiently compact the DNA, first the DNA is 'turned off' and then very tightly wound (or
      compacted) into toroids (like small tires) which are stacked one on top of another. During
      this process of compaction the DNA will occasionally break or fragment. The egg can repair
      the DNA fragmentation as long as there is not a large amount of breakage. If the DNA
      fragmentation exceeds a certain amount then fertilization and early development of the embryo
      may be adversely affected. DNA fragmentation can be tested by using the Sperm Chromatin
      Structure Assay (SCSA), which the investigators currently measure in males who present with
      their partners with infertility. Previous studies have suggested that the abnormalities in
      sperm due to vitamin D deficiency may be related to increased DNA fragmentation. This study
      will assist in understanding the cause of sperm abnormalities in subjects with Vitamin D
      deficiency.

      This is a prospective, cohort study. In this study male patients who present with inability
      to conceive will be asked to be involved in this study. After agreement with the study, a
      blood sample drawn which will be tested for Vitamin D level. The investigators will then
      compare sperm DNA fragmentation between normal Vitamin D levels, Vitamin D insufficiency, and
      Vitamin D deficiency. All infertile males presenting to the investigators' infertility clinic
      have a Semen analysis and Sperm chromatin Structure Assay (SCSA). The research part of the
      study will be to obtain the Vitamin D level.
observational model: Cohort
time perspective: Prospective
measure: Sperm DNA Fragmentation
time frame: 1 year
description: Human Sperm DNA fragmentation will be determined by the Sperm Chromatin Structure Assay.
measure: High DNA stainability
time frame: 1 year
description: High DNA stainability is determined by the Sperm Chromatin Structure Assay and is consistent with immature sperm.
measure: Sperm density
time frame: 1 year
description: This will be determined by microscopic analysis of participant's semen and expressed as millions per milliliter
measure: Sperm motility
time frame: 1 year
description: This will be determined by microscopic analysis of participant's semen and expressed as percent motile.
measure: Sperm morphology
time frame: 1 year
description: This will be determined by microscopic analysis of participant's semen and will be expressed as percent normal forms.
measure: Height
time frame: 1 year
description: Measured by stadiometer and recorded in centimeters.
measure: Weight
time frame: 1 year
description: Measured using digital, medical scale
measure: BMI
time frame: 1 year
description: weight and height will be combined to report BMI in kg/m^2
measure: Tobacco status
time frame: 1 year
description: Patient will be asked if uses tobacco products: smoke, smokeless
measure: Race/ethnicity
time frame: 1 year
description: Patient will self identify race/ethnicity
arm group label: Vitamin D deficiency
description: The study group will be males discovered to have Vitamin D deficiency.
arm group label: Control group
description: The control group will be males with normal Vitamin D status
intervention type: Diagnostic Test
intervention name: Vitamin D
description: Blood will be drawn for Vitamin D level
arm group label: Control group
arm group label: Vitamin D deficiency
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Male
minimum age: 21 Years
maximum age: 56 Years
last name: Keith A Hansen, MD
phone: 6053288839
email: Keith.Hansen@SanfordHealth.org
last name: Angela Haldeman, RN
phone: 6053288800
email: Angela.Haldeman@SanfordHealth.org
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
citation: Blomberg Jensen M, Bjerrum PJ, Jessen TE, Nielsen JE, Joensen UN, Olesen IA, Petersen JH, Juul A, Dissing S, Jorgensen N. Vitamin D is positively associated with sperm motility and increases intracellular calcium in human spermatozoa. Hum Reprod. 2011 Jun;26(6):1307-17. doi: 10.1093/humrep/der059. Epub 2011 Mar 22.
PMID: 21427118
citation: Bunde E, Hanssen K, Huntington MK. Vitamin D status in eastern South Dakota. S D Med. 2012 Jun;65(6):227, 229, 231.
PMID: 22856011
citation: Boisen IM, Bollehuus Hansen L, Mortensen LJ, Lanske B, Juul A, Blomberg Jensen M. Possible influence of vitamin D on male reproduction. J Steroid Biochem Mol Biol. 2017 Oct;173:215-222. doi: 10.1016/j.jsbmb.2016.09.023. Epub 2016 Sep 28.
PMID: 27693423
citation: Blomberg Jensen M, Lawaetz JG, Petersen JH, Juul A, Jorgensen N. Effects of Vitamin D Supplementation on Semen Quality, Reproductive Hormones, and Live Birth Rate: A Randomized Clinical Trial. J Clin Endocrinol Metab. 2018 Mar 1;103(3):870-881. doi: 10.1210/jc.2017-01656.
PMID: 29126319
citation: Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Guidelines for preventing and treating vitamin D deficiency and insufficiency revisited. J Clin Endocrinol Metab. 2012 Apr;97(4):1153-8. doi: 10.1210/jc.2011-2601. Epub 2012 Mar 22. No abstract available.
PMID: 22442274
responsible party type: Principal Investigator
investigator affiliation: Sanford Health
investigator full name: Keith Hansen
investigator title: Principal Investigator
mesh term: Infertility
mesh term: Infertility, Male
mesh term: Vitamin D Deficiency
mesh term: Vitamin D
sharing ipd: Yes
ipd description: Plan to share individual participant data (IPD) with researchers who desire information.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: The data will be available after collection complete and will remain available for 3 years.
ipd access criteria: Investigator.