Clinical trial NCT04405960: Role of Alphacalcidol Supplement to Reduce Pain and COMP in Geriatric Knee Osteoarthritis Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Osteoarthritis, Knee
Aged
Keywords: Vitamin D
Alfacalcidol
Knee osteoarthritis pain
Cartilage Oligomeric Matrix Protein
Lead sponsor: Syarif Hidayatullah State Islamic University Jakarta
Sponsor class: OTHER
First posted: 2020-05-28
Enrollment: 146
Sex: ALL
Minimum age (years): 60
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: WOMAC Pain Score Difference
timeFrame: Initial and final week (week 0 and 12).
measure: Cartilage Oligomeric Matrix Protein Difference
timeFrame: Initial and final week (week 0 and 12).
Secondary outcomes:
measure: Serum 25(OH)D Concentration Difference
timeFrame: Initial and final week (week 0 and 12).
measure: Body Mass Index
timeFrame: Once, on week-0
measure: Kellgren-Lawrence Knee OA Grade
timeFrame: Once, on week-0
measure: Mean Physical Activity
timeFrame: Every 2 weeks (from week-0 until week-12)
measure: Mean Sun Exposure Frequency
timeFrame: Every 2 weeks (from week-0 until week-12)
measure: Mean Vitamin D Consumption
timeFrame: Every 4 weeks (from week-0 until week-12)
Other outcomes:
Locations:
city: South Tangerang
country: Indonesia
facility: Public Health Service Clinic Reni Jaya
state: Banten
Study officials:
affiliation: Faculty of Medicine Syarif Hidayatullah State Islamic University Jakarta
name: Achmad Zaki, PhD
role: PRINCIPAL_INVESTIGATOR
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