<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/NCT03761290</url>
  </required_header>
  <id_info>
    <org_study_id>Shoemaker R03</org_study_id>
    <nct_id>NCT03761290</nct_id>
  </id_info>
  <brief_title>Glucose Homeostasis in Pseudohypoparathyroidism</brief_title>
  <official_title>Glucose Homeostasis and Beta Cell Function in Pseudohypoparathyroidism</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Vanderbilt University Medical Center</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>
      It is increasingly recognized that Pseudohypoparathyroidism type 1A (PHP1A) is associated&#xD;
      with an increased risk of type 2 diabetes but the mechanism is unknown. In this pilot study&#xD;
      we will assess β-cell function in patients with PHP1A and pseudopseudohypoparathyroidism&#xD;
      PPHP.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pseudohypoparathyroidism type 1A (PHP1A) is a rare, genetic disorder caused by impaired&#xD;
      stimulatory G-protein signaling due to heterozygous mutations in the gene, GNAS. The most&#xD;
      severe form of the disease, PHP1A occurs when a GNAS mutation is inherited on the&#xD;
      preferentially expressed maternal allele. A less severe form of the disease,&#xD;
      pseudopseudohypoparathyroidism (PPHP), occurs when a GNAS mutation is inherited on the&#xD;
      paternal allele. Clinically, PHP1A is characterized by multi-hormone resistance, cognitive&#xD;
      impairment and early-onset obesity while PPHP has a mild phenotype without multi-hormone&#xD;
      resistance. It is increasingly recognized that PHP1A is associated with an increased risk of&#xD;
      type 2 diabetes but the mechanism is unknown. Glucose homeostasis and diabetes risk has not&#xD;
      been studied in PPHP. As part of the parent K23 award, we investigated glucose tolerance in&#xD;
      children with PHP1A. In contrast to the adult literature, we found that children with PHP1A&#xD;
      had greater insulin sensitivity than matched controls. When challenged with an oral glucose&#xD;
      load, however, children with PHP1A had persistent hyperglycemia and 25% met criteria for&#xD;
      impaired glucose tolerance. The goal of this proposal is to quantify β-cell function in&#xD;
      PHP1A. It is plausible that these individuals have a) impaired β-cell function, b)&#xD;
      differences in insulin sensitivity, and c) impaired incretin function. Thus, in this pilot&#xD;
      study we will definitively assess one of these, β-cell function, using the frequently sampled&#xD;
      intravenous glucose tolerance test in patients with PHP1A and PPHP (aim 1). We will also&#xD;
      assess oral glucose tolerance over time by bringing back children and young adults with PHP1A&#xD;
      from our original cohort for repeat glucose tolerance testing (aim 2). The ultimate goal is&#xD;
      to rigorously define glucose homeostasis defects in PHP1A in order to design and conduct an&#xD;
      intervention study for glucose intolerance and type 2 diabetes in PHP1A.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    COVID precautions prevented enrollment of healthy controls, funding ended.&#xD;
  </why_stopped>
  <start_date type="Actual">June 19, 2019</start_date>
  <completion_date type="Actual">April 30, 2021</completion_date>
  <primary_completion_date type="Actual">April 30, 2021</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>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Insulin sensitivity (Si)</measure>
    <time_frame>baseline</time_frame>
  </primary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">14</enrollment>
  <condition>Pseudohypoparathyroidism and Pseudopseudohypoparathyroidism</condition>
  <condition>Pseudohypoparathyroidism Type Ia</condition>
  <condition>Albright Hereditary Osteodystrophy</condition>
  <arm_group>
    <arm_group_label>Pseudphypoparathyroidism type 1A (PHP1A)</arm_group_label>
    <description>Case</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pseudopseudohypoparathyroidism (PPHP)</arm_group_label>
    <description>Case</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Controls</arm_group_label>
    <description>Matched control group</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with PHP1A/PPHP and matched controls&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Diagnosis of PHP1A/PPHP&#xD;
&#xD;
          2. Age between 6 and 50 years old&#xD;
&#xD;
        Controls will be matched based on:&#xD;
&#xD;
          1. Gender&#xD;
&#xD;
          2. Race&#xD;
&#xD;
          3. Age (±2 years if &lt;25 years old or ±5 years if ≥25 years old)&#xD;
&#xD;
          4. BMI (±2 kg/m2)&#xD;
&#xD;
          5. Diabetes status&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Treatment with appetite-altering drug or initiation of a new weight loss program in&#xD;
             the past 3 months&#xD;
&#xD;
          2. Type 1 diabetes&#xD;
&#xD;
          3. Type 2 diabetes treated with insulin or GLP-1 receptor agonists or A1c &gt;9%at their&#xD;
             most recent clinic visit&#xD;
&#xD;
          4. Pregnant or lactating women&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Ashley H Shoemaker, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vanderbilt University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.facebook.com/pseudohypoparathyroidism</url>
    <description>Vanderbilt PHP Research Page</description>
  </link>
  <reference>
    <citation>Perez KM, Curley KL, Slaughter JC, Shoemaker AH. Glucose Homeostasis and Energy Balance in Children With Pseudohypoparathyroidism. J Clin Endocrinol Metab. 2018 Nov 1;103(11):4265-4274. doi: 10.1210/jc.2018-01067.</citation>
    <PMID>30085125</PMID>
  </reference>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>November 29, 2018</study_first_submitted>
  <study_first_submitted_qc>November 29, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 3, 2018</study_first_posted>
  <last_update_submitted>May 26, 2021</last_update_submitted>
  <last_update_submitted_qc>May 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 27, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt University Medical Center</investigator_affiliation>
    <investigator_full_name>Ashley Shoemaker</investigator_full_name>
    <investigator_title>Assistant Professor of Pediatrics</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pseudohypoparathyroidism</mesh_term>
    <mesh_term>Pseudopseudohypoparathyroidism</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/NCT03761290
org study id: Shoemaker R03
nct id: NCT03761290
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
It is increasingly recognized that Pseudohypoparathyroidism type 1A (PHP1A) is associated
      with an increased risk of type 2 diabetes but the mechanism is unknown. In this pilot study
      we will assess β-cell function in patients with PHP1A and pseudopseudohypoparathyroidism
      PPHP.
Pseudohypoparathyroidism type 1A (PHP1A) is a rare, genetic disorder caused by impaired
      stimulatory G-protein signaling due to heterozygous mutations in the gene, GNAS. The most
      severe form of the disease, PHP1A occurs when a GNAS mutation is inherited on the
      preferentially expressed maternal allele. A less severe form of the disease,
      pseudopseudohypoparathyroidism (PPHP), occurs when a GNAS mutation is inherited on the
      paternal allele. Clinically, PHP1A is characterized by multi-hormone resistance, cognitive
      impairment and early-onset obesity while PPHP has a mild phenotype without multi-hormone
      resistance. It is increasingly recognized that PHP1A is associated with an increased risk of
      type 2 diabetes but the mechanism is unknown. Glucose homeostasis and diabetes risk has not
      been studied in PPHP. As part of the parent K23 award, we investigated glucose tolerance in
      children with PHP1A. In contrast to the adult literature, we found that children with PHP1A
      had greater insulin sensitivity than matched controls. When challenged with an oral glucose
      load, however, children with PHP1A had persistent hyperglycemia and 25% met criteria for
      impaired glucose tolerance. The goal of this proposal is to quantify β-cell function in
      PHP1A. It is plausible that these individuals have a) impaired β-cell function, b)
      differences in insulin sensitivity, and c) impaired incretin function. Thus, in this pilot
      study we will definitively assess one of these, β-cell function, using the frequently sampled
      intravenous glucose tolerance test in patients with PHP1A and PPHP (aim 1). We will also
      assess oral glucose tolerance over time by bringing back children and young adults with PHP1A
      from our original cohort for repeat glucose tolerance testing (aim 2). The ultimate goal is
      to rigorously define glucose homeostasis defects in PHP1A in order to design and conduct an
      intervention study for glucose intolerance and type 2 diabetes in PHP1A.
observational model: Case-Control
time perspective: Cross-Sectional
measure: Insulin sensitivity (Si)
time frame: baseline
arm group label: Pseudphypoparathyroidism type 1A (PHP1A)
description: Case
arm group label: Pseudopseudohypoparathyroidism (PPHP)
description: Case
arm group label: Controls
description: Matched control group
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 6 Years
maximum age: 50 Years
last name: Ashley H Shoemaker, MD
role: Principal Investigator
affiliation: Vanderbilt University Medical Center
facility: 
country: United States
url: http://www.facebook.com/pseudohypoparathyroidism
description: Vanderbilt PHP Research Page
citation: Perez KM, Curley KL, Slaughter JC, Shoemaker AH. Glucose Homeostasis and Energy Balance in Children With Pseudohypoparathyroidism. J Clin Endocrinol Metab. 2018 Nov 1;103(11):4265-4274. doi: 10.1210/jc.2018-01067.
PMID: 30085125
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt University Medical Center
investigator full name: Ashley Shoemaker
investigator title: Assistant Professor of Pediatrics
mesh term: Pseudohypoparathyroidism
mesh term: Pseudopseudohypoparathyroidism
sharing ipd: No