<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/NCT04405960</url>
  </required_header>
  <id_info>
    <org_study_id>162/UN2.F10/PPM.00.02/2016</org_study_id>
    <nct_id>NCT04405960</nct_id>
  </id_info>
  <brief_title>Role of Alphacalcidol Supplement to Reduce Pain and COMP in Geriatric Knee Osteoarthritis Patients</brief_title>
  <official_title>Role of Vitamin D (Alphacalcidol) Supplement to Reduce Pain and Cartilage Oligomeric Matrix Protein Serum Levels in Geriatric Knee Osteoarthritis Patients: A Randomized, Double-Blind, Placebo-Controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Syarif Hidayatullah State Islamic University Jakarta</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Syarif Hidayatullah State Islamic University Jakarta</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Indonesian population's life expectancy has been increasing steadily in the last 3 decades.&#xD;
      It potentially increases the prevalence of degenerative diseases, including osteoarthritis&#xD;
      (OA). Serum Vitamin D (25(OH)D) level has been recognized as a risk factors for knee OA.&#xD;
      Cartilage Oligomeric Matrix Protein (COMP) is cartilage degradation product can be used as a&#xD;
      diagnostic marker for knee OA. This study aims to determine the effect of Vitamin D&#xD;
      supplementation (Alphacalcidol) on pain based on WOMAC indicators and joint cartilage&#xD;
      condition based on COMP serum markers in knee OA elderly patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Vitamin D plays important role to enhance calcium absorption in intestine and promotes&#xD;
      mineralization of bones. Several studies found that Vitamin D levels were low in patients&#xD;
      with knee OA.&#xD;
&#xD;
      Vitamin D deficiency were found in 50% of women age 45-55 years old and 35% of women age&#xD;
      60-90 years old in Jakarta and Bekasi. Alphacalcidol is a vitamin D supplementation&#xD;
      recommended to be used in patients with renal insufficiency, which is prevalent in elderly.&#xD;
      Alfacalcidol does not need to undergo renal 1-alpha-hydroxylation which impaired in renal&#xD;
      insufficiency, although it can still cause hypercalcemia.&#xD;
&#xD;
      Current detection and diagnosis of knee OA relies on plain radiological examination, which is&#xD;
      not really objective because it depends on radiological expertise and experience. Moreover,&#xD;
      plain radiological diagnosis has limited ability to detect joint damage at an early stage.&#xD;
      Therefore, knee OA is often diagnosed at advanced stage. For this reason, selecting accurate&#xD;
      joint cartilage biomarkers is important to detect and predict the severity of OA objectively&#xD;
      and at earlier stage. Cartilage Oligomeric Matrix Protein (COMP) is one of degradation&#xD;
      products released into synovium fluid and bloodstream from cartilage matrix turnover process.&#xD;
      Therefore, COMP can be used as a marker of diagnosis and cartilage injury severity of knee&#xD;
      OA.&#xD;
&#xD;
      Currently, there has been no study about the association of Vitamin D supplementation with&#xD;
      pain level and cartilage matrix turnover process in Indonesia. Therefore, this study aims to&#xD;
      determine the effect of Vitamin D supplementation (Alphacalcidol) on pain and joint cartilage&#xD;
      condition in elderly patients with knee OA.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2017</start_date>
  <completion_date type="Actual">December 31, 2017</completion_date>
  <primary_completion_date type="Actual">September 30, 2017</primary_completion_date>
  <phase>Phase 3</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>
    <intervention_model_description>This is a randomized, double-blind, and placebo-controlled trials. Elderly subjects with symptomatic knee OA visited our clinic in Jakarta were recruited. Medical history taking, physical examinations, knee radiology, blood test for Vitamin D (25(OH)D), calcium, and COMP serum were performed. Subjects were then randomly allocated to either intervention group to be given 1 µg Alphacalcidol or control group to be given placebo in 12 weeks.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>This study used Contract Research Organization (CRO) Equilab to ensure the quality. In this study, researchers, respondents, interviewers, supplement providers, radiology and laboratory staffs were blinded. The interviewers used a questionnaire that had been prepared previously and was used equally for the intervention and control groups.&#xD;
Knee x-ray examination was performed to determine knee OA severity based on Kellgren-Lawrence grading system. It was carried out using the same method and technique between the intervention and control groups. X-ray examination was carried out at the same hospital's radiology unit and was interpreted blindingly by the same radiologist. Blood examination to measure 25(OH)D and COMP was carried out using the same methods and techniques between the intervention and control groups by staffs from the same certified laboratory.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>WOMAC Pain Score Difference</measure>
    <time_frame>Initial and final week (week 0 and 12).</time_frame>
    <description>Instrument for assessing pain in knee OA patients from The Western Ontario &amp; McMaster University OA Index. WOMAC pain score was assessed every 2 weeks to ensure that subject's pain within inclusion criteria.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cartilage Oligomeric Matrix Protein Difference</measure>
    <time_frame>Initial and final week (week 0 and 12).</time_frame>
    <description>Serum concentration of Cartilage Oligomeric Matrix Protein (COMP) as a biomarker for the severity of knee OA.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Serum 25(OH)D Concentration Difference</measure>
    <time_frame>Initial and final week (week 0 and 12).</time_frame>
    <description>Serum 25(OH)D Concentration as vitamin D deficiency status</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body Mass Index</measure>
    <time_frame>Once, on week-0</time_frame>
    <description>Body mass index, calculated by measuring subject's height and weight</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kellgren-Lawrence Knee OA Grade</measure>
    <time_frame>Once, on week-0</time_frame>
    <description>Radiological knee OA grading system</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Physical Activity</measure>
    <time_frame>Every 2 weeks (from week-0 until week-12)</time_frame>
    <description>Physical activities performed by subjects using their energy related to work and daily leisure time. Measured using Basic Health Research (Riskesdas) 2007 Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Sun Exposure Frequency</measure>
    <time_frame>Every 2 weeks (from week-0 until week-12)</time_frame>
    <description>Ultraviolet B (UVB) exposure between 7-11 am for ≥ 30 minutes with exposure at least to the face and palms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Vitamin D Consumption</measure>
    <time_frame>Every 4 weeks (from week-0 until week-12)</time_frame>
    <description>The amount of Vitamin D consumption by subjects, which is calculated based on the consumption of fruits, vegetables, milk and its processed products, fish, etc.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">146</enrollment>
  <condition>Osteoarthritis, Knee</condition>
  <condition>Aged</condition>
  <arm_group>
    <arm_group_label>Intervention group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Individuals in intervention group were given oral Vitamin D supplements (Alphacalcidol 1 µg) once daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Individuals in control group were given placebo once daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alfacalcidol 1 MCG Oral Capsule</intervention_name>
    <description>The subjects in the intervention group were given 1 µg oral capsule alphacalcidol once daily Subjects in the control group were given placebo once daily with similar capsule shape and color to the capsule given to the intervention group. The process of alphacalcidol and placebo encapsulation were carried out by pharmacists in the pharmacy depot under the supervision of researchers and CRO Equilab. Alphacalcidol and placebo were put into plastic pots containing 30 capsules for every 4 weeks for each subject. The pot had an etiquette written explaining how to consume the drug (after breakfast between 7 - 10 a.m.). The drugs' packaging and code numbering were carried out by CRO Equilab to ensure a double-blind procedure. As a control, each subject was equipped with a monitoring card. Alphacalcidol and placebo were given for 12 weeks without interruption. Monitoring of compliance and side effects was performed by physicians every 2 weeks.</description>
    <arm_group_label>Intervention group</arm_group_label>
    <other_name>Bon-One</other_name>
    <other_name>One-Alpha</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sugar pill</intervention_name>
    <description>The subjects in the control group were given placebo containing simple sugar oral capsule once daily with similar capsule shape and color to the capsule given to the intervention group. The process of alphacalcidol and placebo encapsulation were carried out by pharmacists in the pharmacy depot under the supervision of researchers and CRO Equilab. Alphacalcidol and placebo were put into plastic pots containing 30 capsules for every 4 weeks for each subject. The pot had an etiquette written explaining how to consume the drug (after breakfast between 7 - 10 a.m.). The drugs' packaging and code numbering were carried out by CRO Equilab to ensure a double-blind procedure. As a control, each subject was equipped with a monitoring card. Alphacalcidol and placebo were given for 12 weeks without interruption. Monitoring of compliance and side effects was performed by physicians every 2 weeks.</description>
    <arm_group_label>Control Group</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with knee pain due to OA who meet clinical and radiological criteria&#xD;
             according to Kellgren-Lawrence grade at least 1 month with knee pain of at least 5&#xD;
             measured using the WOMAC pain index&#xD;
&#xD;
          -  Body mass index ≤27 kg/m2&#xD;
&#xD;
          -  Do not have any systemic inflammatory diseases or other systemic diseases from history&#xD;
             taking and physical examination&#xD;
&#xD;
          -  Do not have any other OA in other joints according to physical examination&#xD;
&#xD;
          -  Did not do any heavy physical activity or strenuous exercise for at least 1 month&#xD;
             (last month)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Grade 4 Kellgren-Lawrence&#xD;
&#xD;
          -  WOMAC pain score &gt;15&#xD;
&#xD;
          -  Serum 25(OH)D &gt;125 nmol/L&#xD;
&#xD;
          -  Calcium serum &gt;10.5 mg/dl&#xD;
&#xD;
          -  Diagnosed with rheumatoid or psoriatic arthritis, lupus or cancer, heart or kidney&#xD;
             disorders, vitamin D hypersensitivity.&#xD;
&#xD;
          -  Knee trauma, including injury to the ligament or meniscus before the study&#xD;
&#xD;
          -  Consuming drugs that contain Magnesium (Antacids), Digitalis (Digoxin), Barbiturates&#xD;
             or other anti-convulsants for a long time, which will interact with Vitamin D&#xD;
&#xD;
          -  Currently undergoing vitamin D therapy for the last 30 days&#xD;
&#xD;
          -  Use of other supplements intended to have an effect on cartilage such as glucosamine&#xD;
             and chondroitin sulphate&#xD;
&#xD;
          -  Undergo intra-articular therapy 3 months before the study&#xD;
&#xD;
          -  Consume oral corticosteroids&#xD;
&#xD;
          -  Senile dementia or other signs and symptoms of memory loss&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Achmad Zaki, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Faculty of Medicine Syarif Hidayatullah State Islamic University Jakarta</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Public Health Service Clinic Reni Jaya</name>
      <address>
        <city>South Tangerang</city>
        <state>Banten</state>
        <zip>15417</zip>
        <country>Indonesia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Indonesia</country>
  </location_countries>
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  <verification_date>May 2020</verification_date>
  <study_first_submitted>May 14, 2020</study_first_submitted>
  <study_first_submitted_qc>May 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 28, 2020</study_first_posted>
  <last_update_submitted>May 22, 2020</last_update_submitted>
  <last_update_submitted_qc>May 22, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 28, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Syarif Hidayatullah State Islamic University Jakarta</investigator_affiliation>
    <investigator_full_name>Achmad Zaki</investigator_full_name>
    <investigator_title>Doctor, Orthopedic Surgeon, Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Vitamin D</keyword>
  <keyword>Alfacalcidol</keyword>
  <keyword>Knee osteoarthritis pain</keyword>
  <keyword>Cartilage Oligomeric Matrix Protein</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoarthritis</mesh_term>
    <mesh_term>Osteoarthritis, Knee</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alfacalcidol</mesh_term>
    <mesh_term>Hydroxycholecalciferols</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Author's informed consent does not include IPD sharing agreement.</ipd_description>
  </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/NCT04405960
org study id: 162/UN2.F10/PPM.00.02/2016
nct id: NCT04405960
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Indonesian population's life expectancy has been increasing steadily in the last 3 decades.
      It potentially increases the prevalence of degenerative diseases, including osteoarthritis
      (OA). Serum Vitamin D (25(OH)D) level has been recognized as a risk factors for knee OA.
      Cartilage Oligomeric Matrix Protein (COMP) is cartilage degradation product can be used as a
      diagnostic marker for knee OA. This study aims to determine the effect of Vitamin D
      supplementation (Alphacalcidol) on pain based on WOMAC indicators and joint cartilage
      condition based on COMP serum markers in knee OA elderly patients.
Vitamin D plays important role to enhance calcium absorption in intestine and promotes
      mineralization of bones. Several studies found that Vitamin D levels were low in patients
      with knee OA.

      Vitamin D deficiency were found in 50% of women age 45-55 years old and 35% of women age
      60-90 years old in Jakarta and Bekasi. Alphacalcidol is a vitamin D supplementation
      recommended to be used in patients with renal insufficiency, which is prevalent in elderly.
      Alfacalcidol does not need to undergo renal 1-alpha-hydroxylation which impaired in renal
      insufficiency, although it can still cause hypercalcemia.

      Current detection and diagnosis of knee OA relies on plain radiological examination, which is
      not really objective because it depends on radiological expertise and experience. Moreover,
      plain radiological diagnosis has limited ability to detect joint damage at an early stage.
      Therefore, knee OA is often diagnosed at advanced stage. For this reason, selecting accurate
      joint cartilage biomarkers is important to detect and predict the severity of OA objectively
      and at earlier stage. Cartilage Oligomeric Matrix Protein (COMP) is one of degradation
      products released into synovium fluid and bloodstream from cartilage matrix turnover process.
      Therefore, COMP can be used as a marker of diagnosis and cartilage injury severity of knee
      OA.

      Currently, there has been no study about the association of Vitamin D supplementation with
      pain level and cartilage matrix turnover process in Indonesia. Therefore, this study aims to
      determine the effect of Vitamin D supplementation (Alphacalcidol) on pain and joint cartilage
      condition in elderly patients with knee OA.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a randomized, double-blind, and placebo-controlled trials. Elderly subjects with symptomatic knee OA visited our clinic in Jakarta were recruited. Medical history taking, physical examinations, knee radiology, blood test for Vitamin D (25(OH)D), calcium, and COMP serum were performed. Subjects were then randomly allocated to either intervention group to be given 1 µg Alphacalcidol or control group to be given placebo in 12 weeks.
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: This study used Contract Research Organization (CRO) Equilab to ensure the quality. In this study, researchers, respondents, interviewers, supplement providers, radiology and laboratory staffs were blinded. The interviewers used a questionnaire that had been prepared previously and was used equally for the intervention and control groups.
Knee x-ray examination was performed to determine knee OA severity based on Kellgren-Lawrence grading system. It was carried out using the same method and technique between the intervention and control groups. X-ray examination was carried out at the same hospital's radiology unit and was interpreted blindingly by the same radiologist. Blood examination to measure 25(OH)D and COMP was carried out using the same methods and techniques between the intervention and control groups by staffs from the same certified laboratory.
measure: WOMAC Pain Score Difference
time frame: Initial and final week (week 0 and 12).
description: Instrument for assessing pain in knee OA patients from The Western Ontario & McMaster University OA Index. WOMAC pain score was assessed every 2 weeks to ensure that subject's pain within inclusion criteria.
measure: Cartilage Oligomeric Matrix Protein Difference
time frame: Initial and final week (week 0 and 12).
description: Serum concentration of Cartilage Oligomeric Matrix Protein (COMP) as a biomarker for the severity of knee OA.
measure: Serum 25(OH)D Concentration Difference
time frame: Initial and final week (week 0 and 12).
description: Serum 25(OH)D Concentration as vitamin D deficiency status
measure: Body Mass Index
time frame: Once, on week-0
description: Body mass index, calculated by measuring subject's height and weight
measure: Kellgren-Lawrence Knee OA Grade
time frame: Once, on week-0
description: Radiological knee OA grading system
measure: Mean Physical Activity
time frame: Every 2 weeks (from week-0 until week-12)
description: Physical activities performed by subjects using their energy related to work and daily leisure time. Measured using Basic Health Research (Riskesdas) 2007 Questionnaire
measure: Mean Sun Exposure Frequency
time frame: Every 2 weeks (from week-0 until week-12)
description: Ultraviolet B (UVB) exposure between 7-11 am for ≥ 30 minutes with exposure at least to the face and palms
measure: Mean Vitamin D Consumption
time frame: Every 4 weeks (from week-0 until week-12)
description: The amount of Vitamin D consumption by subjects, which is calculated based on the consumption of fruits, vegetables, milk and its processed products, fish, etc.
arm group label: Intervention group
arm group type: Experimental
description: Individuals in intervention group were given oral Vitamin D supplements (Alphacalcidol 1 µg) once daily
arm group label: Control Group
arm group type: Placebo Comparator
description: Individuals in control group were given placebo once daily
intervention type: Drug
intervention name: Alfacalcidol 1 MCG Oral Capsule
description: The subjects in the intervention group were given 1 µg oral capsule alphacalcidol once daily Subjects in the control group were given placebo once daily with similar capsule shape and color to the capsule given to the intervention group. The process of alphacalcidol and placebo encapsulation were carried out by pharmacists in the pharmacy depot under the supervision of researchers and CRO Equilab. Alphacalcidol and placebo were put into plastic pots containing 30 capsules for every 4 weeks for each subject. The pot had an etiquette written explaining how to consume the drug (after breakfast between 7 - 10 a.m.). The drugs' packaging and code numbering were carried out by CRO Equilab to ensure a double-blind procedure. As a control, each subject was equipped with a monitoring card. Alphacalcidol and placebo were given for 12 weeks without interruption. Monitoring of compliance and side effects was performed by physicians every 2 weeks.
arm group label: Intervention group
other name: Bon-One
other name: One-Alpha
intervention type: Drug
intervention name: Sugar pill
description: The subjects in the control group were given placebo containing simple sugar oral capsule once daily with similar capsule shape and color to the capsule given to the intervention group. The process of alphacalcidol and placebo encapsulation were carried out by pharmacists in the pharmacy depot under the supervision of researchers and CRO Equilab. Alphacalcidol and placebo were put into plastic pots containing 30 capsules for every 4 weeks for each subject. The pot had an etiquette written explaining how to consume the drug (after breakfast between 7 - 10 a.m.). The drugs' packaging and code numbering were carried out by CRO Equilab to ensure a double-blind procedure. As a control, each subject was equipped with a monitoring card. Alphacalcidol and placebo were given for 12 weeks without interruption. Monitoring of compliance and side effects was performed by physicians every 2 weeks.
arm group label: Control Group
other name: Placebo
criteria: 
gender: All
minimum age: 60 Years
maximum age: 80 Years
healthy volunteers: No
last name: Achmad Zaki, PhD
role: Principal Investigator
affiliation: Faculty of Medicine Syarif Hidayatullah State Islamic University Jakarta
facility: 
country: Indonesia
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responsible party type: Principal Investigator
investigator affiliation: Syarif Hidayatullah State Islamic University Jakarta
investigator full name: Achmad Zaki
investigator title: Doctor, Orthopedic Surgeon, Principal Investigator
mesh term: Osteoarthritis
mesh term: Osteoarthritis, Knee
mesh term: Alfacalcidol
mesh term: Hydroxycholecalciferols
sharing ipd: No
ipd description: Author's informed consent does not include IPD sharing agreement.