<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/NCT03840824</url>
  </required_header>
  <id_info>
    <org_study_id>812735</org_study_id>
    <nct_id>NCT03840824</nct_id>
  </id_info>
  <brief_title>Blood Spot Self-administered Test and Assay</brief_title>
  <official_title>Blood Spot Self-administered Test and Assay</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Pennsylvania</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The current study will compare hormone levels of AMH, FSH and inhibin B in blood specimens&#xD;
      collected by venipuncture and fingerstick in a sample of pre-menopausal women ages 18-45&#xD;
      years with normal menstrual cycles.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Recent advances in cancer diagnosis and treatment have led to greater survival rates in&#xD;
      patients with malignancies. However, these life-saving treatments, especially alkylating&#xD;
      agents, often lead to premature ovarian failure, infertility and related long-term health&#xD;
      problems. It is difficult to predict whether, and the extent to which, patients will&#xD;
      experience these problems. There are no early clinical signs of decreased fertility&#xD;
      potential; even young women who maintain cyclic menses after therapy are at high risk of&#xD;
      infertility, early menopause and related health problems. Preliminary studies suggest that&#xD;
      several surrogate measures of fertility potential are different in cancer survivors compared&#xD;
      with controls. These include follicle stimulating hormone (FSH), estradiol, anti-mullerian&#xD;
      hormone (AMH) and inhibin B. Large longitudinal studies are needed to validate these measures&#xD;
      with gold standard outcomes such as pregnancy rates, pregnancy outcomes and time to&#xD;
      menopause. The main impediment to assessing the value of these markers and generating data&#xD;
      that is useful to cancer survivors is the need for frequent and timed blood samples.&#xD;
&#xD;
      Daily or frequent trips to the clinical center are not practical and reduce the compliance of&#xD;
      even the most motivated patients. The hypothesis that will be tested by this study is that&#xD;
      blood spot assays can be developed that provide robust, personalized data for surrogate&#xD;
      markers of reproductive function which can be used to assess reproductive potential in women;&#xD;
      furthermore, bloodspots collected at home are an acceptable method for reproductive hormone&#xD;
      measurement in women with and without a history of cancer. The current study will compare&#xD;
      hormone levels of AMH, FSH and inhibin B in blood specimens collected by venipuncture and&#xD;
      fingerstick in a sample of subjects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2010</start_date>
  <completion_date type="Actual">August 2016</completion_date>
  <primary_completion_date type="Actual">June 2016</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>AMH pg/mL in dried bloodspot vs serum samples</measure>
    <time_frame>Day 1</time_frame>
    <description>Serum AMH ELISA assay results will be compared to capillary blood sample AMH collected on filter paper and dried. Recovery of spiked ligands, sensitivity and specificity of the assays will be also assessed.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adequacy of subject's self-collected bloodspot sample vs. sample collected in clinic</measure>
    <time_frame>Day 1</time_frame>
    <description>A capillary blood sample from a finger-prick is applied to Whatman #903 filter paper, allowed to dry at room temperature for at least 4 hours, and then stored until analysis in the laboratory. Subjects willing to conduct a finger stick at home will collect an additional dried blood spot sample for secondary outcome measures. At home blood spot cards will be compared to those obtained in the office to determine adequacy of collection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measures of user acceptability through subject report/feedback</measure>
    <time_frame>Day 1</time_frame>
    <description>Ease of use data reported by subject survey will be summarized to determine the overall acceptability of bloodspot collection and the potential for at- home use</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AMH pg/mL in cancer survivors vs. healthy control cohorts</measure>
    <time_frame>Day 1</time_frame>
    <description>AMH in dried blood spots vs. serum collected during the early follicular phase in 30 cancer survivors (15 exposed to low dose cancer therapy, 15 exposed to high dose cancer therapy) and 30 healthy similar aged controls will be compared using tests and multivariable linear regression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>FSH (mIU/mL) in dried bloodspot vs serum samples</measure>
    <time_frame>Day 1</time_frame>
    <description>Serum FSH ELISA assay results will be compared to FSH in a dried capillary blood sample applied to filter paper. Recovery of spiked ligands and sensitivity and specificity of the assays will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inhibin B (pg/ml) in dried bloodspot vs serum samples</measure>
    <time_frame>Day 1</time_frame>
    <description>Serum Inhibin B ELISA assay results will be compared to capillary blood sample Inhibin B collected on filter paper and dried. Recovery of spiked ligands and sensitivity and specificity of the assays will be assessed.</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">80</enrollment>
  <condition>Dysfunction; Endocrine</condition>
  <condition>Effects of Chemotherapy</condition>
  <condition>Premature Ovarian Failure</condition>
  <arm_group>
    <arm_group_label>Cancer Survivor</arm_group_label>
    <description>Pre-menopausal women who are cancer survivors ages 18-45 years with normal menstrual cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Similar aged healthy controls</arm_group_label>
    <description>Pre-menopausal, healthy women ages 18-45 years with normal menstrual cycles</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Late Reproductive Age</arm_group_label>
    <description>Pre-menopausal, healthy women of late reproductive age</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      whole blood, serum&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The target population is 80 pre-menopausal women ages 18-45 years with normal menstrual&#xD;
        cycles:&#xD;
&#xD;
        Aim 1: Total 80 subjects:&#xD;
&#xD;
          -  30 cancer survivors&#xD;
&#xD;
          -  30 similar aged healthy controls&#xD;
&#xD;
          -  20 late reproductive aged women&#xD;
&#xD;
        Aim 2: Subset of 60 subjects:&#xD;
&#xD;
          -  30 cancer survivors&#xD;
&#xD;
          -  30 similar aged healthy controls&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult females&#xD;
&#xD;
          -  Age between 18-45 years&#xD;
&#xD;
          -  Premenopausal (defined as menses in the past 12 months)&#xD;
&#xD;
          -  Postmenarchal&#xD;
&#xD;
          -  Presence of an intact uterus and two ovaries&#xD;
&#xD;
          -  Ability and willingness to comply with study protocol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy within the previous 3 months&#xD;
&#xD;
          -  Lactation within the previous 3 months&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clarisa Gracia, MD, MSCE</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pennsylvania</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Pennsylvania, Reproductive Research Unit</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>McDade TW, Woodruff TK, Huang YY, Funk WE, Prewitt M, Kondapalli L, Gracia CR. Quantification of anti-Mullerian hormone (AMH) in dried blood spots: validation of a minimally invasive method for assessing ovarian reserve. Hum Reprod. 2012 Aug;27(8):2503-8. doi: 10.1093/humrep/des194. Epub 2012 Jun 6.</citation>
    <PMID>22674205</PMID>
  </reference>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>March 17, 2015</study_first_submitted>
  <study_first_submitted_qc>February 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <last_update_submitted>February 10, 2020</last_update_submitted>
  <last_update_submitted_qc>February 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 11, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>healthy</keyword>
  <keyword>premenopausal</keyword>
  <keyword>postmenarchal</keyword>
  <keyword>chemotherapy</keyword>
  <keyword>alkylating agent</keyword>
  <keyword>alkylator</keyword>
  <keyword>high dose cancer therapy</keyword>
  <keyword>low dose cancer therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Primary Ovarian Insufficiency</mesh_term>
    <mesh_term>Menopause, Premature</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/NCT03840824
org study id: 812735
nct id: NCT03840824
lead sponsor: 
has dmc: No
The current study will compare hormone levels of AMH, FSH and inhibin B in blood specimens
      collected by venipuncture and fingerstick in a sample of pre-menopausal women ages 18-45
      years with normal menstrual cycles.
Recent advances in cancer diagnosis and treatment have led to greater survival rates in
      patients with malignancies. However, these life-saving treatments, especially alkylating
      agents, often lead to premature ovarian failure, infertility and related long-term health
      problems. It is difficult to predict whether, and the extent to which, patients will
      experience these problems. There are no early clinical signs of decreased fertility
      potential; even young women who maintain cyclic menses after therapy are at high risk of
      infertility, early menopause and related health problems. Preliminary studies suggest that
      several surrogate measures of fertility potential are different in cancer survivors compared
      with controls. These include follicle stimulating hormone (FSH), estradiol, anti-mullerian
      hormone (AMH) and inhibin B. Large longitudinal studies are needed to validate these measures
      with gold standard outcomes such as pregnancy rates, pregnancy outcomes and time to
      menopause. The main impediment to assessing the value of these markers and generating data
      that is useful to cancer survivors is the need for frequent and timed blood samples.

      Daily or frequent trips to the clinical center are not practical and reduce the compliance of
      even the most motivated patients. The hypothesis that will be tested by this study is that
      blood spot assays can be developed that provide robust, personalized data for surrogate
      markers of reproductive function which can be used to assess reproductive potential in women;
      furthermore, bloodspots collected at home are an acceptable method for reproductive hormone
      measurement in women with and without a history of cancer. The current study will compare
      hormone levels of AMH, FSH and inhibin B in blood specimens collected by venipuncture and
      fingerstick in a sample of subjects.
observational model: Cohort
time perspective: Prospective
measure: AMH pg/mL in dried bloodspot vs serum samples
time frame: Day 1
description: Serum AMH ELISA assay results will be compared to capillary blood sample AMH collected on filter paper and dried. Recovery of spiked ligands, sensitivity and specificity of the assays will be also assessed.
measure: Adequacy of subject's self-collected bloodspot sample vs. sample collected in clinic
time frame: Day 1
description: A capillary blood sample from a finger-prick is applied to Whatman #903 filter paper, allowed to dry at room temperature for at least 4 hours, and then stored until analysis in the laboratory. Subjects willing to conduct a finger stick at home will collect an additional dried blood spot sample for secondary outcome measures. At home blood spot cards will be compared to those obtained in the office to determine adequacy of collection.
measure: Measures of user acceptability through subject report/feedback
time frame: Day 1
description: Ease of use data reported by subject survey will be summarized to determine the overall acceptability of bloodspot collection and the potential for at- home use
measure: AMH pg/mL in cancer survivors vs. healthy control cohorts
time frame: Day 1
description: AMH in dried blood spots vs. serum collected during the early follicular phase in 30 cancer survivors (15 exposed to low dose cancer therapy, 15 exposed to high dose cancer therapy) and 30 healthy similar aged controls will be compared using tests and multivariable linear regression
measure: FSH (mIU/mL) in dried bloodspot vs serum samples
time frame: Day 1
description: Serum FSH ELISA assay results will be compared to FSH in a dried capillary blood sample applied to filter paper. Recovery of spiked ligands and sensitivity and specificity of the assays will be assessed.
measure: Inhibin B (pg/ml) in dried bloodspot vs serum samples
time frame: Day 1
description: Serum Inhibin B ELISA assay results will be compared to capillary blood sample Inhibin B collected on filter paper and dried. Recovery of spiked ligands and sensitivity and specificity of the assays will be assessed.
arm group label: Cancer Survivor
description: Pre-menopausal women who are cancer survivors ages 18-45 years with normal menstrual cycles.
arm group label: Similar aged healthy controls
description: Pre-menopausal, healthy women ages 18-45 years with normal menstrual cycles
arm group label: Late Reproductive Age
description: Pre-menopausal, healthy women of late reproductive age
whole blood, serum
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Clarisa Gracia, MD, MSCE
role: Principal Investigator
affiliation: University of Pennsylvania
facility: 
country: United States
citation: McDade TW, Woodruff TK, Huang YY, Funk WE, Prewitt M, Kondapalli L, Gracia CR. Quantification of anti-Mullerian hormone (AMH) in dried blood spots: validation of a minimally invasive method for assessing ovarian reserve. Hum Reprod. 2012 Aug;27(8):2503-8. doi: 10.1093/humrep/des194. Epub 2012 Jun 6.
PMID: 22674205
responsible party type: Sponsor
mesh term: Primary Ovarian Insufficiency
mesh term: Menopause, Premature