<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/NCT03819140</url>
  </required_header>
  <id_info>
    <org_study_id>18-24705</org_study_id>
    <nct_id>NCT03819140</nct_id>
  </id_info>
  <brief_title>Continuous Versus Cyclical OCP Use in PCOS</brief_title>
  <acronym>CCOUP</acronym>
  <official_title>Continuous Versus Cyclical OCP Use in PCOS: A Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of California, San Francisco</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The mainstay treatment for females with Polycystic Ovary Syndrome (PCOS) has long been a&#xD;
      combination of an oral contraceptive pill or OCP (containing both estrogen and progestin)&#xD;
      along with an anti-androgen medication (such as Spironolactone) to not only prevent chronic&#xD;
      anovulation but also suppress elevated testosterone levels and its clinical effects on the&#xD;
      body. While there are multiple OCPs available on the market today and several studies that&#xD;
      look at different progestins and their anti-androgenicity, not much is known about whether&#xD;
      the length of active pills in OCP therapy (3 weeks versus 6 months) has any further benefit&#xD;
      in continued suppression of testosterone and subsequently improvement in clinical findings of&#xD;
      hyperandrogenism in the PCOS population. In this pilot randomized open label clinical trial,&#xD;
      females between the ages of 16 and 35 years diagnosed with PCOS based on the Rotterdam&#xD;
      Criteria, and not currently on medical therapy with an OCP will be enrolled in the study and&#xD;
      randomized to either a continuous 6 month OCP or cyclical 21 day active OCP therapy. Our aim&#xD;
      is to conduct a pilot randomized clinical trial to determine the effect of 6 months of active&#xD;
      monophasic OCPs on testosterone levels and cutaneous findings of hyperandrogenism (hirsutism&#xD;
      and acne) as compared to a traditional 21 day active/7 day placebo OCP in women with PCOS.&#xD;
      These findings will be compared over a 6 month period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Those who meet criteria to take part in the study (women between the ages of 16-35 years,&#xD;
      diagnosed with PCOS and have findings of hyperandrogenism either by serum testosterone levels&#xD;
      above the normal reference range or by their modified Ferriman Gallwey score of &gt;8, and are&#xD;
      recommended to start an oral contraceptive pill for therapy) and give consent, will be&#xD;
      randomized into either of two oral contraceptive (OCP) treatment groups:&#xD;
&#xD;
        1. Ethinyl estradiol 30 mcg-Drospirenone 3 mg (Yasmin): 168 days of active hormone pills&#xD;
           (no placebo pills) for 6 months.&#xD;
&#xD;
        2. Ethinyl estradiol 30 mcg-Drospirenone 3mg (Yasmin): 21 days of active + 7 days of&#xD;
           placebo pills for 6 months&#xD;
&#xD;
      Participants will be given the OCP Yasmin with instructions to take the medication at the&#xD;
      same time each day for the length of the study (6 months). On the 4th, 12th and 24th week of&#xD;
      therapy (roughly the 1st, 3rd and 6th month), blood work will be drawn and is detailed below.&#xD;
&#xD;
      At 1 month into therapy, (near the end of the 4th week on an OCP) both treatment groups will&#xD;
      be expected to get blood work (total and free testosterone, SHBG, estradiol, LH, and FSH&#xD;
      levels will be checked). At the time of the blood draw, subjects in the cyclical group should&#xD;
      be on placebo/sugar pills and those in the continuous group on active hormone pills.&#xD;
&#xD;
      At 3 months into therapy, participants will come back to the PCOS clinic for routine care&#xD;
      follow up and be seen by a Reproductive Endocrinology and Fertility specialist. This visit is&#xD;
      considered &quot;standard of care&quot; and not specific to the study. However, during this visit a&#xD;
      study investigator will also touch base briefly with the participants to see how they are&#xD;
      doing. An online survey (through REDCap) will also be sent to participants that addresses if&#xD;
      they have missed any doses of their medication and assess their acne quality of life. In&#xD;
      addition, participants will once again get blood work (including total and free testosterone,&#xD;
      SHBG, estradiol, LH, FSH, fasting lipid panel, fasting serum glucose, insulin, and HbA1c). As&#xD;
      before, the cyclical group should be on placebo/sugar pills at the time of blood draw and the&#xD;
      continuous group on active hormone pills.&#xD;
&#xD;
      At 6 months into therapy, participants will come in for a study visit (this is not considered&#xD;
      routine care) in which they will have their vitals taken, a physical exam that includes a&#xD;
      re-evaluation of their mFG score, and an in-clinic pelvic ultrasound to assess ovarian volume&#xD;
      and follicle counts. They will also be emailed a post-study survey through REDCap, that&#xD;
      includes a quality of life questionnaire for both acne and hirsutism, and includes questions&#xD;
      regarding satisfaction with current therapy and any missed doses of their medication. Lastly,&#xD;
      participants will again be expected to get blood work (total and free testosterone, SHBG,&#xD;
      estradiol, LH, FSH).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 1, 2019</start_date>
  <completion_date type="Actual">October 16, 2022</completion_date>
  <primary_completion_date type="Actual">October 16, 2022</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in biochemical hyperandrogenism</measure>
    <time_frame>measured at baseline, 1 month, 3 months and 6 months into therapy</time_frame>
    <description>Testosterone level</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in clinical findings of hyperandrogenism - Hirsutism</measure>
    <time_frame>Baseline and at 6 months into therapy</time_frame>
    <description>Participants will be examined and scored using the modified Ferriman-Gallwey Hirsutism. score. This scoring system is considered the standard scoring system that defines hirsutism (excess male pattern hair growth on the body) quantitatively. There are 9 body areas measured on a scare of 0-4, with higher values indicative of significant hair growth. All subscales are combined for a total score, with a minimum score of 0 and max of 36. A total score of &gt;/=8 is considered diagnostic for hirsutism.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metabolic changes with OCP therapy</measure>
    <time_frame>Baseline and at 3 months into therapy</time_frame>
    <description>Diabetes risk will be assessed and compared in both treatment arms by measuring HOMA-IR (through insulin and fasting glucose) as well as HbA1c percentage.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Polycystic Ovary Syndrome</condition>
  <arm_group>
    <arm_group_label>Continuous OCP Therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants randomly assigned to this arm will receive 8 packs of a 21 day oral contraceptive pills (OCP) called Yasmin (3 mg Drospirenone/0.03 mg Ethinyl estradiol) which comes in a formulation of 21 days of active hormone and 7 days of sugar pills. In this arm, participants will only be expected to take active hormone pills (colored pills) for the 6 months straight without stopping or taking the sugar pills in each pack.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cyclical OCP Therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants randomly assigned to this arm will receive 6 packs of a 21 day oral contraceptive pill (OCP) called Yasmin (3 mg Drospirenone/0.03 mg Ethinyl estradiol) which has 21 days of active hormone and 7 days of sugar pills. Participants will take one pill daily for 6 months and be expected to take the sugar pills at the end of each monthly pack prior to starting a new pack.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Yasmin</intervention_name>
    <description>Participants in each treatment arm will receive the medication Yasmin. However only the Cyclical OCP Therapy arm will take the sugar pills designated each month in the pill packs and the Continuous OCP Therapy arm will not.</description>
    <arm_group_label>Continuous OCP Therapy</arm_group_label>
    <arm_group_label>Cyclical OCP Therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria: To be included in this study, participants must be:&#xD;
&#xD;
          1. Female, within 15-40 years of age&#xD;
&#xD;
          2. Diagnosed with Polycystic Ovary Syndrome based on the 2003 Rotterdam Criteria (must&#xD;
             meet 2 out of 3 criteria):&#xD;
&#xD;
               1. evidence of either biochemical or clinical hyperandrogenism (elevated free and or&#xD;
                  total testosterone level above the normal reference range for assay, and/or an&#xD;
                  modified Ferriman-Gallwey hirsutism score &gt;8)&#xD;
&#xD;
               2. Oligo- or anovulation&#xD;
&#xD;
               3. Polycystic ovary morphology on ultrasound&#xD;
&#xD;
          3. Adolescents should be at least 2 years out from menarche (first menstrual period).&#xD;
&#xD;
          4. Participants must not be on an oral contraceptive pill (OCP) at the start of the study&#xD;
             and or Spironolactone therapy (an anti-androgen medication), but recommended by their&#xD;
             physician to start OCP therapy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Females with Polycystic Ovary Syndrome (PCOS) who do not have either biochemical&#xD;
             (elevated total or free testosterone levels) or clinical (modified Ferriman-Gallwey&#xD;
             hirsutism score &lt;8) findings of hyperandrogenism will not be included in the study as&#xD;
             this is one of the primary outcome measures.&#xD;
&#xD;
          2. Females with PCOS who are already on and currently using a form of contraceptive&#xD;
             (oral, vaginal ring, or patch)&#xD;
&#xD;
          3. Females that are concurrently using or plan to use an anti-androgenic medication such&#xD;
             as Spironolactone in the next 6 months.&#xD;
&#xD;
          4. Females currently or are planning to obtain permanent hair removal (ex. laser hair&#xD;
             removal, electrolysis) in the concurrent 6 months of starting oral contraceptive (OCP)&#xD;
             therapy will also be excluded from the study&#xD;
&#xD;
          5. Women who are pregnant or have contraindications for starting an OCP, including active&#xD;
             smokers, history of clotting disorders, history of deep vein thrombosis or blood&#xD;
             clots, neoplasia, vascular disease, migraines, hypertension, or have renal/hepatic&#xD;
             disease will be excluded from the study as OCP therapy would not be indicated or&#xD;
             approved in this population.&#xD;
&#xD;
          6. Females with elevated potassium levels above the normal reference range for age.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>15 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Heather Huddleston, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94158</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Legro RS, Pauli JG, Kunselman AR, Meadows JW, Kesner JS, Zaino RJ, Demers LM, Gnatuk CL, Dodson WC. Effects of continuous versus cyclical oral contraception: a randomized controlled trial. J Clin Endocrinol Metab. 2008 Feb;93(2):420-9. doi: 10.1210/jc.2007-2287. Epub 2007 Dec 4.</citation>
    <PMID>18056769</PMID>
  </reference>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>November 29, 2018</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>January 6, 2023</last_update_submitted>
  <last_update_submitted_qc>January 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hyperandrogenism</keyword>
  <keyword>Oral Contraceptive Pills</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Polycystic Ovary Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Drospirenone and ethinyl estradiol combination</mesh_term>
  </intervention_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/NCT03819140
org study id: 18-24705
nct id: NCT03819140
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The mainstay treatment for females with Polycystic Ovary Syndrome (PCOS) has long been a
      combination of an oral contraceptive pill or OCP (containing both estrogen and progestin)
      along with an anti-androgen medication (such as Spironolactone) to not only prevent chronic
      anovulation but also suppress elevated testosterone levels and its clinical effects on the
      body. While there are multiple OCPs available on the market today and several studies that
      look at different progestins and their anti-androgenicity, not much is known about whether
      the length of active pills in OCP therapy (3 weeks versus 6 months) has any further benefit
      in continued suppression of testosterone and subsequently improvement in clinical findings of
      hyperandrogenism in the PCOS population. In this pilot randomized open label clinical trial,
      females between the ages of 16 and 35 years diagnosed with PCOS based on the Rotterdam
      Criteria, and not currently on medical therapy with an OCP will be enrolled in the study and
      randomized to either a continuous 6 month OCP or cyclical 21 day active OCP therapy. Our aim
      is to conduct a pilot randomized clinical trial to determine the effect of 6 months of active
      monophasic OCPs on testosterone levels and cutaneous findings of hyperandrogenism (hirsutism
      and acne) as compared to a traditional 21 day active/7 day placebo OCP in women with PCOS.
      These findings will be compared over a 6 month period.
Those who meet criteria to take part in the study (women between the ages of 16-35 years,
      diagnosed with PCOS and have findings of hyperandrogenism either by serum testosterone levels
      above the normal reference range or by their modified Ferriman Gallwey score of >8, and are
      recommended to start an oral contraceptive pill for therapy) and give consent, will be
      randomized into either of two oral contraceptive (OCP) treatment groups:

        1. Ethinyl estradiol 30 mcg-Drospirenone 3 mg (Yasmin): 168 days of active hormone pills
           (no placebo pills) for 6 months.

        2. Ethinyl estradiol 30 mcg-Drospirenone 3mg (Yasmin): 21 days of active + 7 days of
           placebo pills for 6 months

      Participants will be given the OCP Yasmin with instructions to take the medication at the
      same time each day for the length of the study (6 months). On the 4th, 12th and 24th week of
      therapy (roughly the 1st, 3rd and 6th month), blood work will be drawn and is detailed below.

      At 1 month into therapy, (near the end of the 4th week on an OCP) both treatment groups will
      be expected to get blood work (total and free testosterone, SHBG, estradiol, LH, and FSH
      levels will be checked). At the time of the blood draw, subjects in the cyclical group should
      be on placebo/sugar pills and those in the continuous group on active hormone pills.

      At 3 months into therapy, participants will come back to the PCOS clinic for routine care
      follow up and be seen by a Reproductive Endocrinology and Fertility specialist. This visit is
      considered "standard of care" and not specific to the study. However, during this visit a
      study investigator will also touch base briefly with the participants to see how they are
      doing. An online survey (through REDCap) will also be sent to participants that addresses if
      they have missed any doses of their medication and assess their acne quality of life. In
      addition, participants will once again get blood work (including total and free testosterone,
      SHBG, estradiol, LH, FSH, fasting lipid panel, fasting serum glucose, insulin, and HbA1c). As
      before, the cyclical group should be on placebo/sugar pills at the time of blood draw and the
      continuous group on active hormone pills.

      At 6 months into therapy, participants will come in for a study visit (this is not considered
      routine care) in which they will have their vitals taken, a physical exam that includes a
      re-evaluation of their mFG score, and an in-clinic pelvic ultrasound to assess ovarian volume
      and follicle counts. They will also be emailed a post-study survey through REDCap, that
      includes a quality of life questionnaire for both acne and hirsutism, and includes questions
      regarding satisfaction with current therapy and any missed doses of their medication. Lastly,
      participants will again be expected to get blood work (total and free testosterone, SHBG,
      estradiol, LH, FSH).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in biochemical hyperandrogenism
time frame: measured at baseline, 1 month, 3 months and 6 months into therapy
description: Testosterone level
measure: Change in clinical findings of hyperandrogenism - Hirsutism
time frame: Baseline and at 6 months into therapy
description: Participants will be examined and scored using the modified Ferriman-Gallwey Hirsutism. score. This scoring system is considered the standard scoring system that defines hirsutism (excess male pattern hair growth on the body) quantitatively. There are 9 body areas measured on a scare of 0-4, with higher values indicative of significant hair growth. All subscales are combined for a total score, with a minimum score of 0 and max of 36. A total score of >/=8 is considered diagnostic for hirsutism.
measure: Metabolic changes with OCP therapy
time frame: Baseline and at 3 months into therapy
description: Diabetes risk will be assessed and compared in both treatment arms by measuring HOMA-IR (through insulin and fasting glucose) as well as HbA1c percentage.
arm group label: Continuous OCP Therapy
arm group type: Active Comparator
description: Participants randomly assigned to this arm will receive 8 packs of a 21 day oral contraceptive pills (OCP) called Yasmin (3 mg Drospirenone/0.03 mg Ethinyl estradiol) which comes in a formulation of 21 days of active hormone and 7 days of sugar pills. In this arm, participants will only be expected to take active hormone pills (colored pills) for the 6 months straight without stopping or taking the sugar pills in each pack.
arm group label: Cyclical OCP Therapy
arm group type: Active Comparator
description: Participants randomly assigned to this arm will receive 6 packs of a 21 day oral contraceptive pill (OCP) called Yasmin (3 mg Drospirenone/0.03 mg Ethinyl estradiol) which has 21 days of active hormone and 7 days of sugar pills. Participants will take one pill daily for 6 months and be expected to take the sugar pills at the end of each monthly pack prior to starting a new pack.
intervention type: Drug
intervention name: Yasmin
description: Participants in each treatment arm will receive the medication Yasmin. However only the Cyclical OCP Therapy arm will take the sugar pills designated each month in the pill packs and the Continuous OCP Therapy arm will not.
arm group label: Continuous OCP Therapy
arm group label: Cyclical OCP Therapy
criteria: 
gender: Female
minimum age: 15 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Heather Huddleston, MD
role: Principal Investigator
affiliation: University of California, San Francisco
facility: 
country: United States
citation: Legro RS, Pauli JG, Kunselman AR, Meadows JW, Kesner JS, Zaino RJ, Demers LM, Gnatuk CL, Dodson WC. Effects of continuous versus cyclical oral contraception: a randomized controlled trial. J Clin Endocrinol Metab. 2008 Feb;93(2):420-9. doi: 10.1210/jc.2007-2287. Epub 2007 Dec 4.
PMID: 18056769
responsible party type: Sponsor
mesh term: Polycystic Ovary Syndrome
mesh term: Drospirenone and ethinyl estradiol combination
sharing ipd: No