<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/NCT02204826</url>
  </required_header>
  <id_info>
    <org_study_id>KRG-infertility</org_study_id>
    <nct_id>NCT02204826</nct_id>
  </id_info>
  <brief_title>Effects of Korean Red Ginseng on Semen Parameters in Male Infertility Patients: a Randomized, Placebo-controlled, Double-blind Clinical Study</brief_title>
  <official_title>Effects of Korean Red Ginseng on Semen Parameters in Male Infertility Patients: a Randomized, Placebo-controlled, Double-blind Clinical Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pusan National University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pusan National University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Korean Red ginseng (KRG) has long been applied to various diseases as a health-promoting&#xD;
      herbal medicine in Korea. Many clinical studies of ginseng have been performed to elucidate&#xD;
      its therapeutic characteristics. KRG has been shown to be effective in many diseases, such as&#xD;
      cancers, hypertension, Alzheimer's disease, diabetes, acquired immune deficiency syndrome,&#xD;
      and sexual dysfunction. Several studies have indicated effects of ginseng on improving&#xD;
      spermatogenesis in animals. The major mechanisms behind these effects were speculated to be&#xD;
      anti-oxidant and anti-aging effects, as well as modulation of the&#xD;
      hypothalamus-pituitary-testis axis [7 - 10]. However, there have been no controlled human&#xD;
      clinical trials to evaluate the effects of KRG on spermatogenesis in patients with male&#xD;
      infertility.&#xD;
&#xD;
      Only a small proportion of causes of male infertility are currently curable, including male&#xD;
      hypogonadal disorders that can be cured by gonadotropic agents, and obstructive azoospermia&#xD;
      that can be corrected by surgery. In addition, evidence-based medicine has revealed that most&#xD;
      empirical treatments are ineffective. Similarly, the efficacies of carnitine, anti-estrogens,&#xD;
      kallikrein, vitamins C and E, and glutathione have not been confirmed.&#xD;
&#xD;
      Therefore, the investigators investigated the effects of KRG on semen parameters in male&#xD;
      infertility patients. This is the first placebo-controlled trial to evaluate the therapeutic&#xD;
      effects of KRG in male patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>April 2011</start_date>
  <completion_date type="Actual">December 2013</completion_date>
  <primary_completion_date type="Actual">February 2012</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Semen parmaters change from baseline to post-treatment</measure>
    <time_frame>Before treatment, After 14 weeks (12 week treatment and 2 week wash out periond)</time_frame>
    <description>1) sperm concentration, 2) percent motility, 3) sperm viability, and 4) Kruger/strict morphology using World Health Organization (WHO) methodologies (4th edition).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in hormonal parameters after treatment</measure>
    <time_frame>Before treatment, After 14 weeks (12 week treatment and 2 week wash out periond)</time_frame>
    <description>Serum concentrations of FSH and LH were measured using chemiluminescence assays, and serum total testosterone was quantified by radioimmunoassay. The hormonal status of all patients was recorded at the initial screening visit and post-treatment.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">80</enrollment>
  <condition>Male Infertility</condition>
  <arm_group>
    <arm_group_label>V + KRG group (n = 20)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>three capsules of KRG (500 mg/dose) daily and varicocelectomy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>non-V + KRG group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>three capsules of KRG (500 mg/dose) daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>V + P group (n = 20)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>placebo capsules and varicocelectomy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>non-V + P group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>non-V + P group (n = 20) placebo capsules</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Korean Red Ginseng (KRG)</intervention_name>
    <description>The KRG capsules were provided by Korean Ginseng Corporation (Daejeon, Korea). KRG powder was manufactured from roots of a 6-year-old red ginseng, Panax ginseng Meyer, harvested in Republic of Korea. KRG was made by steaming fresh ginseng at 90-100 ◦C for 3 h and then drying at 50-80 ◦C.&#xD;
KRG powder prepared from grinded red ginseng (KRG capsule : 500mg/capsule). KRG was analyzed by high-performance liquid chromatography. KRG extract contained major ginsenoside-Rb1: 4.26mg/g, -Rb2: 1.62mg/g, -Rc: 1.80mg/g, -Rd: 0.29mg/g, -Re: 1.71mg/g, -Rf: 0.67mg/g, -Rg1: 2.61mg/g, -Rg2: 0.20mg/g, -Rg3: 0.13mg/g, and other minor ginsenosides. During the study period, three capsules were taken daily for 12 weeks.</description>
    <arm_group_label>V + KRG group (n = 20)</arm_group_label>
    <arm_group_label>non-V + KRG group</arm_group_label>
    <arm_group_label>non-V + P group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Varicocelectomy</intervention_name>
    <description>Surgical microscope-assisted varicocelectomy using the subinguinal approach was conducted by a single surgeon.</description>
    <arm_group_label>V + KRG group (n = 20)</arm_group_label>
    <arm_group_label>V + P group (n = 20)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients should be males, 25 - 45 years of age, who had complained of infertility for&#xD;
             at least 12 months, and had no history of surgical or medical treatments for&#xD;
             infertility.&#xD;
&#xD;
          -  Increased retrograde flow in the internal spermatic vein with venous diameter &gt; 3 mm&#xD;
             during the Valsalva maneuver on scrotal ultrasonography was used as an indicator of&#xD;
             varicocele [13].&#xD;
&#xD;
          -  Varicocele was graded according to the criteria presented by Lyon et al. [14]: *Grade&#xD;
             I, palpable only with the Valsalva maneuver&#xD;
&#xD;
               -  Grade II, palpable without the Valsalva maneuver&#xD;
&#xD;
               -  Grade III, visible from a distance.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A history of vasectomy or obstructive azoospermia&#xD;
&#xD;
          -  Chromosomal abnormalities&#xD;
&#xD;
          -  Hypogonadism or pituitary abnormalities&#xD;
&#xD;
          -  Anatomical abnormality of the genitals&#xD;
&#xD;
          -  Significant hepatopathy (liver enzymes elevated 2 - 3-fold higher than the normal&#xD;
             range)&#xD;
&#xD;
          -  Renal insufficiency (serum creatinine level &gt; 2.5 mg/dL)&#xD;
&#xD;
          -  Medical treatment for infertility during the past 4 weeks.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hyun Jun Park, PhD, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Urology, Pusan National University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Urology, Pusan National University Hospital</name>
      <address>
        <city>Busan</city>
        <zip>602-739</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>April 24, 2014</study_first_submitted>
  <study_first_submitted_qc>July 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 30, 2014</study_first_posted>
  <last_update_submitted>August 27, 2018</last_update_submitted>
  <last_update_submitted_qc>August 27, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 29, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Pusan National University Hospital</investigator_affiliation>
    <investigator_full_name>Hyun Jun Park</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Effects of Korean Red Ginseng on semen parameters in male infertility patients: a randomized, placebo-controlled, double-blind clinical study</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>
  <!-- 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/NCT02204826
org study id: KRG-infertility
nct id: NCT02204826
lead sponsor: 
has dmc: Yes
Korean Red ginseng (KRG) has long been applied to various diseases as a health-promoting
      herbal medicine in Korea. Many clinical studies of ginseng have been performed to elucidate
      its therapeutic characteristics. KRG has been shown to be effective in many diseases, such as
      cancers, hypertension, Alzheimer's disease, diabetes, acquired immune deficiency syndrome,
      and sexual dysfunction. Several studies have indicated effects of ginseng on improving
      spermatogenesis in animals. The major mechanisms behind these effects were speculated to be
      anti-oxidant and anti-aging effects, as well as modulation of the
      hypothalamus-pituitary-testis axis [7 - 10]. However, there have been no controlled human
      clinical trials to evaluate the effects of KRG on spermatogenesis in patients with male
      infertility.

      Only a small proportion of causes of male infertility are currently curable, including male
      hypogonadal disorders that can be cured by gonadotropic agents, and obstructive azoospermia
      that can be corrected by surgery. In addition, evidence-based medicine has revealed that most
      empirical treatments are ineffective. Similarly, the efficacies of carnitine, anti-estrogens,
      kallikrein, vitamins C and E, and glutathione have not been confirmed.

      Therefore, the investigators investigated the effects of KRG on semen parameters in male
      infertility patients. This is the first placebo-controlled trial to evaluate the therapeutic
      effects of KRG in male patients.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Semen parmaters change from baseline to post-treatment
time frame: Before treatment, After 14 weeks (12 week treatment and 2 week wash out periond)
description: 1) sperm concentration, 2) percent motility, 3) sperm viability, and 4) Kruger/strict morphology using World Health Organization (WHO) methodologies (4th edition).
measure: Changes in hormonal parameters after treatment
time frame: Before treatment, After 14 weeks (12 week treatment and 2 week wash out periond)
description: Serum concentrations of FSH and LH were measured using chemiluminescence assays, and serum total testosterone was quantified by radioimmunoassay. The hormonal status of all patients was recorded at the initial screening visit and post-treatment.
arm group label: V + KRG group (n = 20)
arm group type: Experimental
description: three capsules of KRG (500 mg/dose) daily and varicocelectomy.
arm group label: non-V + KRG group
arm group type: Active Comparator
description: three capsules of KRG (500 mg/dose) daily
arm group label: V + P group (n = 20)
arm group type: Active Comparator
description: placebo capsules and varicocelectomy
arm group label: non-V + P group
arm group type: Placebo Comparator
description: non-V + P group (n = 20) placebo capsules
intervention type: Drug
intervention name: Korean Red Ginseng (KRG)
description: The KRG capsules were provided by Korean Ginseng Corporation (Daejeon, Korea). KRG powder was manufactured from roots of a 6-year-old red ginseng, Panax ginseng Meyer, harvested in Republic of Korea. KRG was made by steaming fresh ginseng at 90-100 ◦C for 3 h and then drying at 50-80 ◦C.
KRG powder prepared from grinded red ginseng (KRG capsule : 500mg/capsule). KRG was analyzed by high-performance liquid chromatography. KRG extract contained major ginsenoside-Rb1: 4.26mg/g, -Rb2: 1.62mg/g, -Rc: 1.80mg/g, -Rd: 0.29mg/g, -Re: 1.71mg/g, -Rf: 0.67mg/g, -Rg1: 2.61mg/g, -Rg2: 0.20mg/g, -Rg3: 0.13mg/g, and other minor ginsenosides. During the study period, three capsules were taken daily for 12 weeks.
arm group label: V + KRG group (n = 20)
arm group label: non-V + KRG group
arm group label: non-V + P group
intervention type: Procedure
intervention name: Varicocelectomy
description: Surgical microscope-assisted varicocelectomy using the subinguinal approach was conducted by a single surgeon.
arm group label: V + KRG group (n = 20)
arm group label: V + P group (n = 20)
criteria: 
gender: Male
minimum age: 25 Years
maximum age: 45 Years
healthy volunteers: No
last name: Hyun Jun Park, PhD, MD
role: Principal Investigator
affiliation: Department of Urology, Pusan National University Hospital
facility: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: Pusan National University Hospital
investigator full name: Hyun Jun Park
investigator title: Professor
mesh term: Infertility
mesh term: Infertility, Male