<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/NCT02227264</url>
  </required_header>
  <id_info>
    <org_study_id>2012-005374-57</org_study_id>
    <nct_id>NCT02227264</nct_id>
  </id_info>
  <brief_title>Primary Hyperparathyroidism: Short-term Calcimimetics Treatment - Relevance for Parathyroid Surgery Decisions?</brief_title>
  <official_title>Primary Hyperparathyroidism: Short-term Calcimimetics Treatment - Relevance for Parathyroid Surgery Decisions?</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Karolinska University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Karolinska Institutet</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Karolinska University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with primary hyperparathyroidism (pHPT) often present with fatigue, psychological&#xD;
      and cognitive symptoms. Improvement in these symptoms after parathyroid adenomectomy (PTX)&#xD;
      has been reported. But physicians lack a method to attribute the symptoms to pHPT and to&#xD;
      predict the reversibility after PTX.&#xD;
&#xD;
      This study aims to evaluate short-term calcimimetic treatment as a tool for predicting the&#xD;
      outcome of PTX on muscle strength, quality of life, psychological symptoms, and cognitive&#xD;
      function in patients with pHPT.&#xD;
&#xD;
      Material and Methods: 118 patients scheduled for PTX at Karolinska University Hospital,&#xD;
      Sweden, will have a four week treatment with calcimimetics (Mimpara®) before undergoing&#xD;
      surgery. Biochemicals, muscle strength, quality of life, psychological symptoms and cognitive&#xD;
      function will be analysed at baseline, after four week follow-up and postoperatively.&#xD;
&#xD;
      Hypothesis: The outcome of short-term calcimimetic treatment can predict the outcome of PTX&#xD;
      on muscle strength, quality of life, psychological symptoms, and cognitive function in&#xD;
      patients with pHPT&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study evaluates if short-term treatment with calcimimetics may be used for patients with&#xD;
      PHPT as a relevant guide in the decision of when to choose parathyroid surgery, by predicting&#xD;
      the outcome of surgical treatment.&#xD;
&#xD;
      120 ± 2 patients with primary hyperparathyroidism scheduled for parathyroid surgery will be&#xD;
      included in the study after informed consent and will receive study medication with&#xD;
      cinacalcet, Mimpara® 30 mgx1 for four weeks. In case of persistent hypercalcemia after two&#xD;
      weeks of treatment with Mimpara® 30 mgx1, the dosage of Mimpara® will be increased to 60 mg&#xD;
      daily. During the study drug treatment period, the patients will be followed closely at least&#xD;
      once a week with clinical monitoring and control of serum ionized calcium, given the risk of&#xD;
      side effects and hypocalcemia. If the concentration of ionized calcium in serum will decrease&#xD;
      to a subnormal level (&lt;1.15 mmol/l), the Mimpara® treatment will be discontinued temporarily&#xD;
      and only reinserted in a lower dose (30 mg x 1) if the concentration of ionized calcium&#xD;
      raises over 1.33 mmol/l. The size of the cohort has been decided after power estimations&#xD;
      based on the results in study part A. Both groups will go through the test panel of&#xD;
      self-rating scales described above at four occasions (Figure).&#xD;
&#xD;
      The Outcome to be registered are the changes from baseline to the end of the study medication&#xD;
      period compared to the changes postoperatively, thus the changes between the Visit 2 to Visit&#xD;
      6 and the changes between Visit 2 and Visit 7 and Visit 8 respektively.&#xD;
&#xD;
      Assessments and Procedures Visit 1: Clinical examination (general condition, neck, blood&#xD;
      pressure, cor et pulm). Screening of patients with primary hyperparathyroidism scheduled for&#xD;
      parathyroid surgery. Patient that fulfills inclusion and exclusion criteria will be asked to&#xD;
      participate in the study.&#xD;
&#xD;
      Visit 2: Informed consent is signed. Test panel of self rating scales (Quality of Life&#xD;
      Questionnaire-Core 30 (QLQ-C30), Positive States of Mind (PSOM )and Hospital Anxiety and&#xD;
      Depression scale (HAD), cognitive test (Montreal cognitive assessment (MoCA-Test)) and muscle&#xD;
      strength (Timed stand test). Blood samples are drawn within 2 weeks before and analyzed for:&#xD;
      parathyroid hormone (p-PTH), s-ionized calcium, p-total calcium, p-albumin, p-creatinine,&#xD;
      p-phosphate, s-25-OH-D-vitamin and p-TSH. Initiation of treatment with Mimpara® 30 mg x 1.&#xD;
      Clinical examination (general condition, blood pressure). For fertile women, a pregnancy test&#xD;
      is demanded before enrollment.&#xD;
&#xD;
      Visit 3: Week 1 (± 2 days); blood samples for analysis of ionized calcium. History of&#xD;
      symptoms related to hypocalcemia (paresthesias, cramps, muscle fatigue). Clinical examination&#xD;
      when indicated (general condition, blood pressure).&#xD;
&#xD;
      Visit 4: Week 2 (± 2 days); blood samples for analysis of ionized calcium. History as above.&#xD;
      Mimpara® continued, If the ionized calcium level is &gt;1.33 mmol/l: increase of dosage of&#xD;
      Mimpara® to 30 mg x 2.&#xD;
&#xD;
      Visit 5: Week 3 (± 2 days); blood samples for analysis of ionized calcium. History as above.&#xD;
      Mimpara® treatment completed.&#xD;
&#xD;
      Visit 6 (3): Week 4 (± 2 weeks in study B); Test panel of self rating scales (QLQ-C30, PSOM&#xD;
      and HAD), cognitive test (MoCA-Test) and muscle strength (Timed stand test). Blood samples&#xD;
      are drawn and analyzed for: plasma (p)-PTH, serum(s)-ionized serum calcium, p-total calcium,&#xD;
      p-albumin, p-creatinine, p-phosphate.&#xD;
&#xD;
      Visit 7 (4): Postoperative follow up, 6 (± 1 week) post surgery; Test panel of self rating&#xD;
      scales (QLQ-C30, PSOM and HAD), cognitive test (MoCA-Test) and muscle strength (Timed stand&#xD;
      test). Blood samples are drawn and analyzed for plasma p-PTH, s-ionized calcium, p-total&#xD;
      calcium, p-albumin, p-creatinine, p-phosphate, s-25-OH-D-vitamin and p-TSH.&#xD;
&#xD;
      Visit 8 (5): Postoperatively, 6 months post surgery (± 3 weeks); Test panel of self rating&#xD;
      scales (QLQ-C30, PSOM and HAD), cognitive test (MoCA-Test) and muscle strength (Timed stand&#xD;
      test). Blood samples are drawn and analyzed for plasma (p)-PTH, s-ionized calcium, p-total&#xD;
      calcium, p-albumin, p-creatinine, p-phosphate, s-25-OH-D-vitamin and p-TSH.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>June 2014</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">December 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Predictive outcome in Quality of Life after parathyroidectomy</measure>
    <time_frame>after four weeks of calcimimetic treatment and postoperatively</time_frame>
    <description>Health related quality of life measured by EORTC QLQ-C30 (total score)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Psychological well-being</measure>
    <time_frame>After four weeks of calcimimetic treatment and postoperatively</time_frame>
    <description>Psychological well-being, evaluated with the validated form Positive States of Mind, PSOM</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anxiety and depression</measure>
    <time_frame>After four weeks of calcimimetic treatment and postoperatively</time_frame>
    <description>Depression and anxiety; evaluated with the Hospital Anxiety and Depression (HAD) scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Muscle strength</measure>
    <time_frame>After four weeks of calcimimetic treatment and postoperatively</time_frame>
    <description>Leg muscle strength measured by Timed stand-test (repeated uprise from chair)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biochemical data</measure>
    <time_frame>After four weeks of calcimimetic treatment and postoperatively</time_frame>
    <description>AE/SAE recording and safety blood samples; serum levels of p-PTH, s-ionized calcium, p-total calcium, p-albumin, p-creatinine, p-phosphate, s-25-OH-D and thyroid-stimulating hormone (TSH)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive function</measure>
    <time_frame>after four weeks of calcimimetic treatment and postoperatively</time_frame>
    <description>Cognitive function evaluated with Montreal cognitive assessment (MoCA-test)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">123</enrollment>
  <condition>Primary Hyperparathyroidism</condition>
  <arm_group>
    <arm_group_label>Cinacalcet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cinacalcet, Mimpara®: 30 mgx1 for four weeks. In case of persistent hypercalcemia after two weeks of treatment with Mimpara® 30 mgx1, the dosage of Mimpara® will be increased to 60 mg daily.&#xD;
Second intervention: Parathyroid adenomectomy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cinacalcet</intervention_name>
    <description>Cinacalcet, Mimpara® 30mgx1-2 for 4 weeks</description>
    <arm_group_label>Cinacalcet</arm_group_label>
    <other_name>H05BX01</other_name>
    <other_name>Mimpara®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>parathyroid adenomectomy</intervention_name>
    <description>surgical removal of pathologic parathyroid tissue</description>
    <arm_group_label>Cinacalcet</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Primary hyperparathyroidism&#xD;
&#xD;
          -  Scheduled for parathyroid surgery&#xD;
&#xD;
          -  Age &gt;40&#xD;
&#xD;
          -  Ability to participate in all tests included in the study model&#xD;
&#xD;
          -  Signed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Breast feeding&#xD;
&#xD;
          -  Fertile woman not using contraceptives (IUD or pills)&#xD;
&#xD;
          -  Impaired kidney function, GFR &lt; 40 ml/min&#xD;
&#xD;
          -  Intolerance to Mimpara®&#xD;
&#xD;
          -  Previously treated with Mimpara®&#xD;
&#xD;
          -  Participating in other ongoing clinical study&#xD;
&#xD;
          -  Epilepsy&#xD;
&#xD;
          -  Severe hepatic impairment&#xD;
&#xD;
          -  Hypotension&#xD;
&#xD;
          -  Heart failure (NYHA class 3-4, symptoms with minimal exertion)&#xD;
&#xD;
          -  Medication with ketoconazole (oral) or tricyclic antidepressants&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Inga-Lena Nilsson, M.D., Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Karolinska UH</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Inga-Lena Y Nilsson, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Karolinska UH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Karolinska University Hospital</name>
      <address>
        <city>Stockholm</city>
        <zip>171 76</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <link>
    <url>http://www.karolinska.se/</url>
    <description>Karolinska University Hospital</description>
  </link>
  <link>
    <url>http://ki.se/</url>
    <description>Karolinska Institute</description>
  </link>
  <link>
    <url>http://www.epn.se</url>
    <description>Ethical Review Board</description>
  </link>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>August 17, 2014</study_first_submitted>
  <study_first_submitted_qc>August 27, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 28, 2014</study_first_posted>
  <last_update_submitted>January 6, 2020</last_update_submitted>
  <last_update_submitted_qc>January 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Karolinska University Hospital</investigator_affiliation>
    <investigator_full_name>Inga-Lena Nilsson</investigator_full_name>
    <investigator_title>M.D., Ph.D; Assoc.prof.</investigator_title>
  </responsible_party>
  <keyword>Primary hyperparathyroidism</keyword>
  <keyword>Calcimimetic Agents</keyword>
  <keyword>Parathyroid adenomectomy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperparathyroidism</mesh_term>
    <mesh_term>Hyperparathyroidism, Primary</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parathyroid Hormone</mesh_term>
    <mesh_term>Cinacalcet</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/NCT02227264
org study id: 2012-005374-57
nct id: NCT02227264
lead sponsor: 
collaborator: 
has dmc: Yes
Patients with primary hyperparathyroidism (pHPT) often present with fatigue, psychological
      and cognitive symptoms. Improvement in these symptoms after parathyroid adenomectomy (PTX)
      has been reported. But physicians lack a method to attribute the symptoms to pHPT and to
      predict the reversibility after PTX.

      This study aims to evaluate short-term calcimimetic treatment as a tool for predicting the
      outcome of PTX on muscle strength, quality of life, psychological symptoms, and cognitive
      function in patients with pHPT.

      Material and Methods: 118 patients scheduled for PTX at Karolinska University Hospital,
      Sweden, will have a four week treatment with calcimimetics (Mimpara®) before undergoing
      surgery. Biochemicals, muscle strength, quality of life, psychological symptoms and cognitive
      function will be analysed at baseline, after four week follow-up and postoperatively.

      Hypothesis: The outcome of short-term calcimimetic treatment can predict the outcome of PTX
      on muscle strength, quality of life, psychological symptoms, and cognitive function in
      patients with pHPT
The study evaluates if short-term treatment with calcimimetics may be used for patients with
      PHPT as a relevant guide in the decision of when to choose parathyroid surgery, by predicting
      the outcome of surgical treatment.

      120 ± 2 patients with primary hyperparathyroidism scheduled for parathyroid surgery will be
      included in the study after informed consent and will receive study medication with
      cinacalcet, Mimpara® 30 mgx1 for four weeks. In case of persistent hypercalcemia after two
      weeks of treatment with Mimpara® 30 mgx1, the dosage of Mimpara® will be increased to 60 mg
      daily. During the study drug treatment period, the patients will be followed closely at least
      once a week with clinical monitoring and control of serum ionized calcium, given the risk of
      side effects and hypocalcemia. If the concentration of ionized calcium in serum will decrease
      to a subnormal level (<1.15 mmol/l), the Mimpara® treatment will be discontinued temporarily
      and only reinserted in a lower dose (30 mg x 1) if the concentration of ionized calcium
      raises over 1.33 mmol/l. The size of the cohort has been decided after power estimations
      based on the results in study part A. Both groups will go through the test panel of
      self-rating scales described above at four occasions (Figure).

      The Outcome to be registered are the changes from baseline to the end of the study medication
      period compared to the changes postoperatively, thus the changes between the Visit 2 to Visit
      6 and the changes between Visit 2 and Visit 7 and Visit 8 respektively.

      Assessments and Procedures Visit 1: Clinical examination (general condition, neck, blood
      pressure, cor et pulm). Screening of patients with primary hyperparathyroidism scheduled for
      parathyroid surgery. Patient that fulfills inclusion and exclusion criteria will be asked to
      participate in the study.

      Visit 2: Informed consent is signed. Test panel of self rating scales (Quality of Life
      Questionnaire-Core 30 (QLQ-C30), Positive States of Mind (PSOM )and Hospital Anxiety and
      Depression scale (HAD), cognitive test (Montreal cognitive assessment (MoCA-Test)) and muscle
      strength (Timed stand test). Blood samples are drawn within 2 weeks before and analyzed for:
      parathyroid hormone (p-PTH), s-ionized calcium, p-total calcium, p-albumin, p-creatinine,
      p-phosphate, s-25-OH-D-vitamin and p-TSH. Initiation of treatment with Mimpara® 30 mg x 1.
      Clinical examination (general condition, blood pressure). For fertile women, a pregnancy test
      is demanded before enrollment.

      Visit 3: Week 1 (± 2 days); blood samples for analysis of ionized calcium. History of
      symptoms related to hypocalcemia (paresthesias, cramps, muscle fatigue). Clinical examination
      when indicated (general condition, blood pressure).

      Visit 4: Week 2 (± 2 days); blood samples for analysis of ionized calcium. History as above.
      Mimpara® continued, If the ionized calcium level is >1.33 mmol/l: increase of dosage of
      Mimpara® to 30 mg x 2.

      Visit 5: Week 3 (± 2 days); blood samples for analysis of ionized calcium. History as above.
      Mimpara® treatment completed.

      Visit 6 (3): Week 4 (± 2 weeks in study B); Test panel of self rating scales (QLQ-C30, PSOM
      and HAD), cognitive test (MoCA-Test) and muscle strength (Timed stand test). Blood samples
      are drawn and analyzed for: plasma (p)-PTH, serum(s)-ionized serum calcium, p-total calcium,
      p-albumin, p-creatinine, p-phosphate.

      Visit 7 (4): Postoperative follow up, 6 (± 1 week) post surgery; Test panel of self rating
      scales (QLQ-C30, PSOM and HAD), cognitive test (MoCA-Test) and muscle strength (Timed stand
      test). Blood samples are drawn and analyzed for plasma p-PTH, s-ionized calcium, p-total
      calcium, p-albumin, p-creatinine, p-phosphate, s-25-OH-D-vitamin and p-TSH.

      Visit 8 (5): Postoperatively, 6 months post surgery (± 3 weeks); Test panel of self rating
      scales (QLQ-C30, PSOM and HAD), cognitive test (MoCA-Test) and muscle strength (Timed stand
      test). Blood samples are drawn and analyzed for plasma (p)-PTH, s-ionized calcium, p-total
      calcium, p-albumin, p-creatinine, p-phosphate, s-25-OH-D-vitamin and p-TSH.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Health Services Research
masking: None (Open Label)
measure: Predictive outcome in Quality of Life after parathyroidectomy
time frame: after four weeks of calcimimetic treatment and postoperatively
description: Health related quality of life measured by EORTC QLQ-C30 (total score)
measure: Psychological well-being
time frame: After four weeks of calcimimetic treatment and postoperatively
description: Psychological well-being, evaluated with the validated form Positive States of Mind, PSOM
measure: Anxiety and depression
time frame: After four weeks of calcimimetic treatment and postoperatively
description: Depression and anxiety; evaluated with the Hospital Anxiety and Depression (HAD) scale
measure: Muscle strength
time frame: After four weeks of calcimimetic treatment and postoperatively
description: Leg muscle strength measured by Timed stand-test (repeated uprise from chair)
measure: Biochemical data
time frame: After four weeks of calcimimetic treatment and postoperatively
description: AE/SAE recording and safety blood samples; serum levels of p-PTH, s-ionized calcium, p-total calcium, p-albumin, p-creatinine, p-phosphate, s-25-OH-D and thyroid-stimulating hormone (TSH)
measure: Cognitive function
time frame: after four weeks of calcimimetic treatment and postoperatively
description: Cognitive function evaluated with Montreal cognitive assessment (MoCA-test)
arm group label: Cinacalcet
arm group type: Experimental
description: Cinacalcet, Mimpara®: 30 mgx1 for four weeks. In case of persistent hypercalcemia after two weeks of treatment with Mimpara® 30 mgx1, the dosage of Mimpara® will be increased to 60 mg daily.
Second intervention: Parathyroid adenomectomy.
intervention type: Drug
intervention name: Cinacalcet
description: Cinacalcet, Mimpara® 30mgx1-2 for 4 weeks
arm group label: Cinacalcet
other name: H05BX01
other name: Mimpara®
intervention type: Procedure
intervention name: parathyroid adenomectomy
description: surgical removal of pathologic parathyroid tissue
arm group label: Cinacalcet
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Inga-Lena Nilsson, M.D., Ph.D
role: Principal Investigator
affiliation: Karolinska UH
last name: Inga-Lena Y Nilsson, MD, PhD
role: Principal Investigator
affiliation: Karolinska UH
facility: 
country: Sweden
url: http://www.karolinska.se/
description: Karolinska University Hospital
url: http://ki.se/
description: Karolinska Institute
url: http://www.epn.se
description: Ethical Review Board
responsible party type: Principal Investigator
investigator affiliation: Karolinska University Hospital
investigator full name: Inga-Lena Nilsson
investigator title: M.D., Ph.D; Assoc.prof.
mesh term: Hyperparathyroidism
mesh term: Hyperparathyroidism, Primary
mesh term: Parathyroid Hormone
mesh term: Cinacalcet
sharing ipd: No