The Effectiveness of Vitamin D Supplementation in Patients With End-stage Knee Osteoarthritis

NCT ID: NCT05981534

Last Updated: 2024-03-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-17
• Study Completion Date: 2025-11-30

Brief Summary

Osteoarthritis (OA) knee is one of the commonest chronic degenerative conditions. It causes disability in elderlies due to pain and stiffness. The prevalence of radiologic knee osteoarthritis increases in proportion to age, reaching an astounding 64.1% for patients who are over 60 years of age. In 2021, there were over 26,000 patients on the Hospital Authority (HA) waiting list for knee total knee replacement (TKR) and with only 4300 TKRs performed, the nominal waiting time for TKR was almost 89 months.

Low vitamin D can adversely affect cartilage thickness and study suggested that low serum vitamin D is associated with increased radiographic knee OA progression. A systematic review concluded that vitamin D supplements can improve pain and function in patients with knee OA.

Vitamin D has long been recognized for its effect on musculoskeletal health and increasing attention has been focused for its effect on muscle function. Vitamin D have a direct effect on muscle hypertrophy by acting on specific vitamin D receptors (VDRs) on myocytes, and sufficient levels of vitamin D in patients have been found to correlate with an increase in the size, number, and strength of muscle fibres. Vitamin D also seems to exert beneficial effects by its interplay with myokines such as myostatin and irisin.

One study also showed that muscle nuclear VDR was increased by 30% and augmented muscle fibre size by 10% in elderly females (mean age of 78 years) taking vitamin D orally at a rate of 100 µg/day (4000 IU/day) for 4 months.

This will be a double-blinded RCT investigating the effect of vitamin D supplements or knee muscle strength, physical function, pain symptoms and, sarcopenia status. The study will be a follow-up study with assessment at baseline, 3- ,6-and 12-months post vitamin D intervention.

Detailed Description

Osteoarthritis (OA) knee is one of the common chronic degenerative conditions. It causes disability in elders, leading to pain and stiffness. The prevalence of radiologic knee osteoarthritis and symptomatic knee OA were 37.4% and 12.1% among adults over 60 years of age.

Often, patients with end-stage knee OA often adopt a sedentary lifestyle to avoid joint pain and stiffness. This can have an adverse effect on muscle function both locally around the knees as well as on generalized muscle health. Ageing and inactivity leads to a progressive loss of muscle mass and strength until an abnormally low level, termed "sarcopenia". Sarcopenic elderlies are more likely to develop deterioration of functional outcomes and higher mortality resulting in socioeconomic and healthcare burdens. In contrast, our previous study investigating the prevalence of sarcopenia in end-stage OA showed that 32.8% of severe knee OA patients also suffered sarcopenia, and these patients showed a slower recovery after undergoing TKR.

Vitamin D has long been recognized for its effect on musculoskeletal health, and increasing attention has been focused on its effect on muscle function. Vitamin D directly affects muscle hypertrophy by acting on specific vitamin D receptors (VDRs) in myocytes, and sufficient vitamin D levels in patients have been found to correlate with an increase in the size, number, and strength of muscle fibers. In the Chinese population aged over 65, 30.6% of the population studied presented with vitamin D deficiency (25(OH)D <20 ng/mL). A systematic review concluded that vitamin D supplements can improve pain and function in patients with knee OA. Moreover, patients with end stage OA knees will have more pain, leading to decreased mobility, a higher risk of sarcopenia, and vitamin D insufficiency that would warrant attention.

56 patients with end-stage knee OA scheduled for TKR will be recruited from the Li Ka Shing Orthopaedic Specialist clinic at the Prince of Wales Hospital (PWH) Hong Kong.

Oral and written consents will be obtained from individuals who agree to participate in the study.

The recruitment period will last for 12 months and the whole project period is 2 years in total. Basic demographics, sarcopenia assessment and Outcome Measurement Questionnaires will be carried out. The patients will be advised to avoid taking supplements and keep a record of medication intake throughout the study period.

We will use 4000 IU/day, for 6 months adapted from previous study. All study tablets including the placebo will be manufactured according to Good Manufacturing Practice (GMP) guidelines for quality assurance.

Assessments including quadriceps and hamstring muscle strength, handgrip strength, 6-meter timed walking gait test, chair stand test, muscle mass using Dual Energy X-ray Absorptiometry and questionnaires will be conducted.

Conditions

Vitamin D Deficiency; Sarcopenia; Knee Osteoarthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Intervention group

The intervention group will receive vitamin D supplement for 6 months

Group Type: EXPERIMENTAL

Vitamin D

Intervention Type: DRUG

4000IU/day vitamin D supplement will be used for 6 months

Control group

The control group will receive placebo for 6 months

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo will be used for 6 months

Interventions

Vitamin D

4000IU/day vitamin D supplement will be used for 6 months

Intervention Type: DRUG

Placebo

Placebo will be used for 6 months

Intervention Type: DRUG

Other Intervention Names

SODX Co., Ltd, Osaka, Japan; SODX Co., Ltd, Osaka, Japan

Eligibility Criteria

Inclusion Criteria

• Male and female patients aged over 50 with end-stage knee OA
• Patient are on the waiting list for TKR at Prince of Wales Hospital
• Walk unaided for 6 meters
• Able to comply with the assessments and has given oral and written consent
• Patients with vitamin D insufficiency and deficiency at the baseline measurement (25(OH)D <30 ng/mL)

Exclusion Criteria

• Patients with connective tissue disorders or myositis condition
• History of any Hip & Knee surgery
• Patients with malnutrition were assessed by Mini-Nutritional assessment.
• Patients with acute immobility (i.e., post-hip fracture or post-acute hospital admission)
• Patient scheduled for TKR within six months
• Patients already taking vitamin D supplements
• Patients with a known contraindication to vitamin D treatment (such as allergy)
• Patients who have renal impairment with glomerular filtration rate (eGFR) < 30 ml/minute

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Prof. Tim-Yun Michael ONG

Clinical Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael Tim-Yun ONG

Role: PRINCIPAL_INVESTIGATOR

Chinese University of Hong Kong

Locations

Prince of Wales Hospital

Hong Kong, , Hong Kong

Site Status: RECRUITING

Countries

Hong Kong

Central Contacts

Michael Tim-Yun ONG, MSc

Role: CONTACT

michael.ong@cuhk.edu.hk

26364171

26364171 ONG, MSc

Role: CONTACT

michael.ong@cuhk.edu.hk

26364171

Facility Contacts

Michael Tim-Yun ONG

Role: primary

michael.ong@cuhk.edu.hk

26364171

References

Wang QW, Ong MT, Man GC, Yeung YM, He X, Choi BC, Ng JP, Mok DK, Lam TP, Yung PS. The effectiveness of vitamin D supplementation in patients with end-stage knee osteoarthritis: Study protocol for a double-blinded, randomized controlled trial. PLoS One. 2024 Oct 21;19(10):e0309610. doi: 10.1371/journal.pone.0309610. eCollection 2024.

Reference Type: DERIVED

PMID: 39432457 (View on PubMed)

Other Identifiers

2022.252

Identifier Type: -

Identifier Source: org_study_id