<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/NCT03038516</url>
  </required_header>
  <id_info>
    <org_study_id>Palliative-D</org_study_id>
    <nct_id>NCT03038516</nct_id>
  </id_info>
  <brief_title>'Palliative-D' Vitamin D to Palliative Cancer Patients</brief_title>
  <acronym>Palliative-D</acronym>
  <official_title>'Palliative-D' Vitamin D Supplementation to Palliative Cancer Patients - A Double Blind, Randomised Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Region Stockholm</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Region Stockholm</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      To test the hypothesis that vitamin D treatment during 12 weeks to palliative cancer patients&#xD;
      can decrease opioid consumption, fatigue and infectious burden and increase quality of life.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PROTOCOL IDENTITY AND OBJECTIVES: EudraCT Number 2017-000268-14 Protocol Title: Vitamin D&#xD;
      supplementation to palliative cancer patients - A double blind, randomised controlled trial.&#xD;
      Acronym: &quot;Palliative-D&quot; Trial Objectives: To test the hypothesis that vitamin D treatment&#xD;
      during 12 weeks to palliative cancer patients can decrease opioid consumption, fatigue and&#xD;
      infectious burden and increase quality of life.&#xD;
&#xD;
      INVESTIGATIONAL MEDICINAL PRODUCTS (IMP): Test ProductDetremin, MA holder Renapharma;&#xD;
      Pharmaceutical Form: Oil Route of Administration: Oral route&#xD;
&#xD;
      METHODOLOGY Trial Design: Double-blind, parallel randomised and placebo controlled trial&#xD;
      Dose/Duration 4000 IU/day for 12 weeks&#xD;
&#xD;
      Primary Endpoint:&#xD;
&#xD;
      The decline of opioid-consumption during 12 weeks in the vitamin D group compared to the&#xD;
      placebo group, based on 3 measurements with 4 weeks intervals.&#xD;
&#xD;
      Secondary end Points:&#xD;
&#xD;
        1. Decline in antibiotic consumption&#xD;
&#xD;
        2. Improvement in quality of life&#xD;
&#xD;
        3. Improvement in fatigue&#xD;
&#xD;
        4. Vitamin D levels in serum after 12 weeks&#xD;
&#xD;
        5. Association between opioid dose and genetic polymorphism in genes involved in the effect&#xD;
           and metabolism of vitamin D in the body.&#xD;
&#xD;
      Efficacy Parameters:&#xD;
&#xD;
      Opioid dose, translated to fentanyl per hour measured at baseline and at week 4,8 and 12.&#xD;
&#xD;
      Antibiotic consumption expressed as % of days with antibiotics during the last 4 weeks&#xD;
      measured at baseline and at week 4, 8 and 12.&#xD;
&#xD;
      Quality of Life measured with EORTC-QLQ-C15-PAL at baseline and after 12 weeks. Fatigue&#xD;
      measured with EORTC-QLQ-C15-PAL at baseline and after 12 weeks. 25-hydroxyvitamin D levels in&#xD;
      blood at baseline and after 12 weeks. ESAS (Edmonton Symptom Assessment Scale ) measured at&#xD;
      baseline and at week 4, 8 and 12.&#xD;
&#xD;
      Safety Parameters: S-calcium will be controlled in all subjects at baseline, at week 4, 8 and&#xD;
      12 and U-calcium in selected cases Power: The least clinically meaningful effect is estimated&#xD;
      to be a 20% decline in opioid dose compared to the placebo. To obtain this result with 80%&#xD;
      power the number of patients is estimated to be 127 in each arm i.e. 254 patients in total.&#xD;
      This includes a drop-out of 25% per group.&#xD;
&#xD;
      Statistical Analyse plan: The primary endpoint will be analysed using linear regression,&#xD;
      using bias corrected and accelerated bootstrap confidence intervals, while controlling for&#xD;
      baseline measure of opioid dose (similar to ANCOVA). Adjustment for other background&#xD;
      variables - such as vitamin D-level at baseline, gender and age - will be made in a secondary&#xD;
      analysis to gain efficiency. The continuous secondary endpoints will be analysed using the&#xD;
      same method as the primary endpoint .&#xD;
&#xD;
      POPULATION OF TRIAL SUBJECTS Number of Subjects: 254 (127 vitamin D and 127 placebo)&#xD;
      Description of Trial Subjects: Palliative Cancer Patients (any cancer form) with a life&#xD;
      expectancy of more than 3 months.&#xD;
&#xD;
      TRIAL TIMETABLE First Subject In Aug 2017 Last Subject In Sept 2019 (25 months to include&#xD;
      participants) Last Subject Out Dec 2019 End of intervention Dec 2019 End of follow up Dec2019&#xD;
      End of Trial: Dec 2020&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 1, 2017</start_date>
  <completion_date type="Actual">June 9, 2020</completion_date>
  <primary_completion_date type="Actual">June 9, 2020</primary_completion_date>
  <phase>Phase 2</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in opioid dose during 12 weeks</measure>
    <time_frame>12 weeks</time_frame>
    <description>The change in decline of opioid-consumption during 12 weeks in the vitamin D group compared to the placebo group, based on 4 measurements with 4 weeks intervals.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Antibiotic Consumption during 12 weeks</measure>
    <time_frame>12weeks</time_frame>
    <description>Change in Antibiotic consumption expressed as % of days with antibiotics during the last 4 weeks measured at baseline and at week 4, 8 and 12.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Quality of life after 12 weeks</measure>
    <time_frame>12 weeks</time_frame>
    <description>Change in Quality of Life measured with EORTC-QLQ-C15-PAL at baseline and after 12 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Fatigue after12 weeks</measure>
    <time_frame>12 weeks</time_frame>
    <description>Change in Fatigue measured with EORTC-QLQ-C15-PAL at baseline and after 12 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in 25-hydroxyvitamin D levels after 12 weeks</measure>
    <time_frame>12 weeks</time_frame>
    <description>Change in 25-hydroxyvitamin D levels in blood at baseline and after 12 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Symptom burden during 12 weeks</measure>
    <time_frame>12 weeks</time_frame>
    <description>Change in Symptom burden measured with ESAS (Edmonton Symptom Assessment Scale) at baseline and at week 4, 8 and 12.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">244</enrollment>
  <condition>Vitamin D Deficiency</condition>
  <arm_group>
    <arm_group_label>Vitamin D</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cholecalciferol (Detremin) solved in MIGLYOL® 812</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>MIGLYOL® 812</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cholecalciferol</intervention_name>
    <description>To test the hypothesis that vitamin D treatment during 12 weeks to palliative cancer patients is superior to placebo in decreasing opioid consumption, fatigue and infectious burden and increase quality of life.</description>
    <arm_group_label>Vitamin D</arm_group_label>
    <other_name>Detremin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>To test the hypothesis that placebo is inferior to vitamin D treatment during 12 weeks to palliative cancer patients in decreasing opioid consumption,</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>MIGLYOL® 812</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients admitted to ASIH Stockholm Södra or Stockholms Sjukhem.&#xD;
&#xD;
          2. Incurable cancer patients with any type of cancer. They could have ongoing oncological&#xD;
             treatment but only with palliative intention. No patients with ongoing oncological&#xD;
             treatment with curative intended treated will be included.&#xD;
&#xD;
          3. The life expectancy should be at least 3 months according to the clinical assessment&#xD;
             of the study physician at the screening visit.&#xD;
&#xD;
          4. The patient should have no cognitive failure, being able to comprehend oral and&#xD;
             written information about the study.&#xD;
&#xD;
          5. 25 OHD &lt; 50 nmol/L.&#xD;
&#xD;
          6. Men and women aged ≥18&#xD;
&#xD;
          7. Signed 'informed consent'&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Ongoing vitamin D supplementation at the time for inclusion.&#xD;
&#xD;
          2. Serum level of 25-OH vitamin D3 &gt;50 nmol/L&#xD;
&#xD;
          3. Known sarkoidosis&#xD;
&#xD;
          4. Treatment with tiazides or digoxin or digitoxin&#xD;
&#xD;
          5. Primary hyperparathyroidism&#xD;
&#xD;
          6. Hypercalcaemia (verified by a laboratory result younger than 2 month)&#xD;
&#xD;
          7. Plans to leave the Stockholm county within 12 weeks of inclusion&#xD;
&#xD;
          8. History of kidney stones&#xD;
&#xD;
          9. Taking part of another clinical study involving drugs&#xD;
&#xD;
         10. Hypersensitivity to cholecalciferol and/or any of the excipients&#xD;
&#xD;
         11. Other criteria that could jeopardize the study or its intention as judged by the&#xD;
             investigator&#xD;
&#xD;
         12. Not being able to perform EORTC-QLQ-C15-PAL or ESAS&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Linda Björkhem-Bergman, Assoc Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stockholm Läns Landsting</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ASIH Stockholm Norr</name>
      <address>
        <city>Solna</city>
        <state>Stockholm</state>
        <zip>171 54</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stockholms Sjukhem ASIH</name>
      <address>
        <city>Stockholm</city>
        <zip>11219</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ASIH Stockholm Södra</name>
      <address>
        <city>Älvsjö</city>
        <zip>12559</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>January 17, 2017</study_first_submitted>
  <study_first_submitted_qc>January 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 31, 2017</study_first_posted>
  <last_update_submitted>September 9, 2020</last_update_submitted>
  <last_update_submitted_qc>September 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 11, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Region Stockholm</investigator_affiliation>
    <investigator_full_name>Linda Björkhem-Bergman</investigator_full_name>
    <investigator_title>MD, PhD, Assoc Prof, Senior Consultant</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin D Deficiency</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cholecalciferol</mesh_term>
    <mesh_term>Vitamin D</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>October 29, 2021</submitted>
    <returned>December 15, 2021</returned>
  </pending_results>
  <!-- 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/NCT03038516
org study id: Palliative-D
nct id: NCT03038516
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
To test the hypothesis that vitamin D treatment during 12 weeks to palliative cancer patients
      can decrease opioid consumption, fatigue and infectious burden and increase quality of life.
PROTOCOL IDENTITY AND OBJECTIVES: EudraCT Number 2017-000268-14 Protocol Title: Vitamin D
      supplementation to palliative cancer patients - A double blind, randomised controlled trial.
      Acronym: "Palliative-D" Trial Objectives: To test the hypothesis that vitamin D treatment
      during 12 weeks to palliative cancer patients can decrease opioid consumption, fatigue and
      infectious burden and increase quality of life.

      INVESTIGATIONAL MEDICINAL PRODUCTS (IMP): Test ProductDetremin, MA holder Renapharma;
      Pharmaceutical Form: Oil Route of Administration: Oral route

      METHODOLOGY Trial Design: Double-blind, parallel randomised and placebo controlled trial
      Dose/Duration 4000 IU/day for 12 weeks

      Primary Endpoint:

      The decline of opioid-consumption during 12 weeks in the vitamin D group compared to the
      placebo group, based on 3 measurements with 4 weeks intervals.

      Secondary end Points:

        1. Decline in antibiotic consumption

        2. Improvement in quality of life

        3. Improvement in fatigue

        4. Vitamin D levels in serum after 12 weeks

        5. Association between opioid dose and genetic polymorphism in genes involved in the effect
           and metabolism of vitamin D in the body.

      Efficacy Parameters:

      Opioid dose, translated to fentanyl per hour measured at baseline and at week 4,8 and 12.

      Antibiotic consumption expressed as % of days with antibiotics during the last 4 weeks
      measured at baseline and at week 4, 8 and 12.

      Quality of Life measured with EORTC-QLQ-C15-PAL at baseline and after 12 weeks. Fatigue
      measured with EORTC-QLQ-C15-PAL at baseline and after 12 weeks. 25-hydroxyvitamin D levels in
      blood at baseline and after 12 weeks. ESAS (Edmonton Symptom Assessment Scale ) measured at
      baseline and at week 4, 8 and 12.

      Safety Parameters: S-calcium will be controlled in all subjects at baseline, at week 4, 8 and
      12 and U-calcium in selected cases Power: The least clinically meaningful effect is estimated
      to be a 20% decline in opioid dose compared to the placebo. To obtain this result with 80%
      power the number of patients is estimated to be 127 in each arm i.e. 254 patients in total.
      This includes a drop-out of 25% per group.

      Statistical Analyse plan: The primary endpoint will be analysed using linear regression,
      using bias corrected and accelerated bootstrap confidence intervals, while controlling for
      baseline measure of opioid dose (similar to ANCOVA). Adjustment for other background
      variables - such as vitamin D-level at baseline, gender and age - will be made in a secondary
      analysis to gain efficiency. The continuous secondary endpoints will be analysed using the
      same method as the primary endpoint .

      POPULATION OF TRIAL SUBJECTS Number of Subjects: 254 (127 vitamin D and 127 placebo)
      Description of Trial Subjects: Palliative Cancer Patients (any cancer form) with a life
      expectancy of more than 3 months.

      TRIAL TIMETABLE First Subject In Aug 2017 Last Subject In Sept 2019 (25 months to include
      participants) Last Subject Out Dec 2019 End of intervention Dec 2019 End of follow up Dec2019
      End of Trial: Dec 2020
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in opioid dose during 12 weeks
time frame: 12 weeks
description: The change in decline of opioid-consumption during 12 weeks in the vitamin D group compared to the placebo group, based on 4 measurements with 4 weeks intervals.
measure: Change in Antibiotic Consumption during 12 weeks
time frame: 12weeks
description: Change in Antibiotic consumption expressed as % of days with antibiotics during the last 4 weeks measured at baseline and at week 4, 8 and 12.
measure: Change in Quality of life after 12 weeks
time frame: 12 weeks
description: Change in Quality of Life measured with EORTC-QLQ-C15-PAL at baseline and after 12 weeks.
measure: Change in Fatigue after12 weeks
time frame: 12 weeks
description: Change in Fatigue measured with EORTC-QLQ-C15-PAL at baseline and after 12 weeks.
measure: Change in 25-hydroxyvitamin D levels after 12 weeks
time frame: 12 weeks
description: Change in 25-hydroxyvitamin D levels in blood at baseline and after 12 weeks.
measure: Change in Symptom burden during 12 weeks
time frame: 12 weeks
description: Change in Symptom burden measured with ESAS (Edmonton Symptom Assessment Scale) at baseline and at week 4, 8 and 12.
arm group label: Vitamin D
arm group type: Active Comparator
description: Cholecalciferol (Detremin) solved in MIGLYOL® 812
arm group label: Placebo
arm group type: Placebo Comparator
description: MIGLYOL® 812
intervention type: Drug
intervention name: Cholecalciferol
description: To test the hypothesis that vitamin D treatment during 12 weeks to palliative cancer patients is superior to placebo in decreasing opioid consumption, fatigue and infectious burden and increase quality of life.
arm group label: Vitamin D
other name: Detremin
intervention type: Device
intervention name: Placebo
description: To test the hypothesis that placebo is inferior to vitamin D treatment during 12 weeks to palliative cancer patients in decreasing opioid consumption,
arm group label: Placebo
other name: MIGLYOL® 812
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Linda Björkhem-Bergman, Assoc Prof
role: Principal Investigator
affiliation: Stockholm Läns Landsting
facility: 
facility: 
facility: 
country: Sweden
responsible party type: Principal Investigator
investigator affiliation: Region Stockholm
investigator full name: Linda Björkhem-Bergman
investigator title: MD, PhD, Assoc Prof, Senior Consultant
mesh term: Vitamin D Deficiency
mesh term: Cholecalciferol
mesh term: Vitamin D
sharing ipd: No
submitted: October 29, 2021
returned: December 15, 2021