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

Osteoarthritis, Knee Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04405960
• Other study ID #: 162/UN2.F10/PPM.00.02/2016
• Status: Completed
• Phase: Phase 3
• Start date: July 1, 2017
• Est. completion date: December 31, 2017

Study information

• Verified date: May 2020
• Source: Syarif Hidayatullah State Islamic University Jakarta
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 146
• Est. completion date: December 31, 2017
• Est. primary completion date: September 30, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Aged
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

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.
• 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.

Locations

Country	Name	City	State
Indonesia	Public Health Service Clinic Reni Jaya	South Tangerang	Banten

Sponsors (1)

Lead Sponsor	Collaborator
Syarif Hidayatullah State Islamic University Jakarta

Country where clinical trial is conducted

Indonesia, 

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* Note: There are 34 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	WOMAC Pain Score Difference	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.	Initial and final week (week 0 and 12).
Primary	Cartilage Oligomeric Matrix Protein Difference	Serum concentration of Cartilage Oligomeric Matrix Protein (COMP) as a biomarker for the severity of knee OA.	Initial and final week (week 0 and 12).
Secondary	Serum 25(OH)D Concentration Difference	Serum 25(OH)D Concentration as vitamin D deficiency status	Initial and final week (week 0 and 12).
Secondary	Body Mass Index	Body mass index, calculated by measuring subject's height and weight	Once, on week-0
Secondary	Kellgren-Lawrence Knee OA Grade	Radiological knee OA grading system	Once, on week-0
Secondary	Mean Physical Activity	Physical activities performed by subjects using their energy related to work and daily leisure time. Measured using Basic Health Research (Riskesdas) 2007 Questionnaire	Every 2 weeks (from week-0 until week-12)
Secondary	Mean Sun Exposure Frequency	Ultraviolet B (UVB) exposure between 7-11 am for = 30 minutes with exposure at least to the face and palms	Every 2 weeks (from week-0 until week-12)
Secondary	Mean Vitamin D Consumption	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.	Every 4 weeks (from week-0 until week-12)

External Links

•   Indonesia Basic Health Research 2007
•   National Economy and Social Survey 2013