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Role of Alphacalcidol Supplement to Reduce Pain and COMP in Geriatric Knee Osteoarthritis Patients

Sponsor
Syarif Hidayatullah State Islamic University Jakarta (Other)
Overall Status
Completed
CT.gov ID
NCT04405960
Collaborator
(none)
146
Enrollment
1
Location
2
Arms
6
Actual Duration (Months)
24.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Alfacalcidol 1 MCG Oral Capsule
  • Drug: Sugar pill
 Phase 3

Detailed Description

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
146 participants
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.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.
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.
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jul 1, 2017
Actual Primary Completion Date :
Sep 30, 2017
Actual Study Completion Date :
Dec 31, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Intervention group

Individuals in intervention group were given oral Vitamin D supplements (Alphacalcidol 1 µg) once daily

Drug: Alfacalcidol 1 MCG Oral Capsule
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.
Other Names:
  • Bon-One
  • One-Alpha

    		•
    Placebo Comparator: Control Group

    Individuals in control group were given placebo once daily

    Drug: Sugar pill
    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.
    Other Names:
  • Placebo

    		•

    Outcome Measures

    Primary Outcome Measures

    1. WOMAC Pain Score Difference [Initial and final week (week 0 and 12).]

      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.

    2. Cartilage Oligomeric Matrix Protein Difference [Initial and final week (week 0 and 12).]

      Serum concentration of Cartilage Oligomeric Matrix Protein (COMP) as a biomarker for the severity of knee OA.

    Secondary Outcome Measures

    1. Serum 25(OH)D Concentration Difference [Initial and final week (week 0 and 12).]

      Serum 25(OH)D Concentration as vitamin D deficiency status

    2. Body Mass Index [Once, on week-0]

      Body mass index, calculated by measuring subject's height and weight

    3. Kellgren-Lawrence Knee OA Grade [Once, on week-0]

      Radiological knee OA grading system

    4. Mean Physical Activity [Every 2 weeks (from week-0 until week-12)]

      Physical activities performed by subjects using their energy related to work and daily leisure time. Measured using Basic Health Research (Riskesdas) 2007 Questionnaire

    5. Mean Sun Exposure Frequency [Every 2 weeks (from week-0 until week-12)]

      Ultraviolet B (UVB) exposure between 7-11 am for ≥ 30 minutes with exposure at least to the face and palms

    6. Mean Vitamin D Consumption [Every 4 weeks (from week-0 until week-12)]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    60 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Patients with knee pain due to OA who meet clinical and radiological criteria according to Kellgren-Lawrence grade at least 1 month with knee pain of at least 5 measured using the WOMAC pain index

    • Body mass index ≤27 kg/m2

    • Do not have any systemic inflammatory diseases or other systemic diseases from history taking and physical examination

    • Do not have any other OA in other joints according to physical examination

    • Did not do any heavy physical activity or strenuous exercise for at least 1 month (last month)

    Exclusion Criteria:

    • Grade 4 Kellgren-Lawrence

    • WOMAC pain score >15

    • Serum 25(OH)D >125 nmol/L

    • Calcium serum >10.5 mg/dl

    • Diagnosed with rheumatoid or psoriatic arthritis, lupus or cancer, heart or kidney disorders, vitamin D hypersensitivity.

    • Knee trauma, including injury to the ligament or meniscus before the study

    • Consuming drugs that contain Magnesium (Antacids), Digitalis (Digoxin), Barbiturates or other anti-convulsants for a long time, which will interact with Vitamin D

    • Currently undergoing vitamin D therapy for the last 30 days

    • Use of other supplements intended to have an effect on cartilage such as glucosamine and chondroitin sulphate

    • Undergo intra-articular therapy 3 months before the study

    • Consume oral corticosteroids

    • Senile dementia or other signs and symptoms of memory loss

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Public Health Service Clinic Reni Jaya South Tangerang Banten Indonesia 15417

    Sponsors and Collaborators

    • Syarif Hidayatullah State Islamic University Jakarta

    Investigators

    • Principal Investigator: Achmad Zaki, PhD, Faculty of Medicine Syarif Hidayatullah State Islamic University Jakarta

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Achmad Zaki, Doctor, Orthopedic Surgeon, Principal Investigator, Syarif Hidayatullah State Islamic University Jakarta
    ClinicalTrials.gov Identifier:
    NCT04405960
    Other Study ID Numbers:
    • 162/UN2.F10/PPM.00.02/2016
    First Posted:
    May 28, 2020
    Last Update Posted:
    May 28, 2020
    Last Verified:
    May 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Achmad Zaki, Doctor, Orthopedic Surgeon, Principal Investigator, Syarif Hidayatullah State Islamic University Jakarta
    Vitamin D
    Alfacalcidol
    Knee osteoarthritis pain
    Cartilage Oligomeric Matrix Protein
    Additional relevant MeSH terms:
    Osteoarthritis
    Osteoarthritis, Knee
    Alfacalcidol
    Hydroxycholecalciferols

    Study Results

    No Results Posted as of May 28, 2020