the Effectiveness of Vitamin D Supplementation on Sarcopenia in Patients With End-stage Knee Osteoarthritis

Sponsor

Chinese University of Hong Kong (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT05981534

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

3.3

Patients Per Site Per Month

Study Details

Study Description

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.

Ageing and inactivity leads to a progressive loss of muscle mass and strength until an abnormally low level, termed as "sarcopenia" (4). Sarcopenic elderlies are more likely to develop deterioration of functional outcomes and higher mortality resulting in socioeconomic and healthcare burdens.

Low vitamin D can adversely affect cartilage thickness and study suggested that low serum vitamin D is associated with increased radiographic knee OA progression (12). 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. It has been shown that elderly individuals with vitamin D deficiency are susceptible to sarcopenia and there are biological, clinical, and epidemiological evidence supporting the association between vitamin D and an increased risk of sarcopenia in older people (14). The 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 (14).

This will be a double-blinded RCT investigating the effect of vitamin D supplements, in addition to exercise, for sarcopenic patients with end-stage knee OA.The study will be a follow-up study with assessment at baseline, 4- and 6-months post vitamin D intervention, 2 months, and 6 months post TKR.

Condition or Disease	Intervention/Treatment	Phase
Vitamin D Deficiency Sarcopenia Knee Osteoarthritis	Drug: Vitamin D Drug: Placebo	N/A

Detailed Description

96 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 (22). This will allow for a full 4 months of vitamin D supplementation before both groups of patients undergoing a standardized physiotherapy program for 4 weeks (8 sessions), and to allow for any potential minor change of TKR date. The final assessments will be performed within 2 weeks, and TKR within 4 weeks after the completion of the physiotherapy program. All study tablets including the placebo will be manufactured according to Good Manufacturing Practice (GMP) guidelines for quality assurance.

Assessments including quadriceps 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

96 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

Double-blinded Randomized Controlled Trial Investigating the Effectiveness of Vitamin D Supplementation on Sarcopenia in Patients With End-stage Knee Osteoarthritis

Actual Study Start Date :

Jul 31, 2023

Anticipated Primary Completion Date :

Jun 30, 2025

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention group The intervention group will recieve vitamin D supplement for 16 weeks plus standardised 4 weeks prehab for TKR.	Drug: Vitamin D 4000IU/day vitamin D supplement will be used for 16 weeks plus standardised 4 weeks prehabilitation for TKR. Other Names: standardised prehabilitation
Placebo Comparator: Control group The control group will recieve placebo for 16 weeks plus standardised 4 weeks prehab for TKR.	Drug: Placebo Placebo will be used for 16 weeks plus standardised 4 weeks prehabilitation for TKR. Other Names: standardised prehabilitation

Arm

Intervention/Treatment

Experimental: Intervention group

The intervention group will recieve vitamin D supplement for 16 weeks plus standardised 4 weeks prehab for TKR.

Drug: Vitamin D

4000IU/day vitamin D supplement will be used for 16 weeks plus standardised 4 weeks prehabilitation for TKR.

Other Names:

standardised prehabilitation

Placebo Comparator: Control group

The control group will recieve placebo for 16 weeks plus standardised 4 weeks prehab for TKR.

Drug: Placebo

Placebo will be used for 16 weeks plus standardised 4 weeks prehabilitation for TKR.

Other Names:

standardised prehabilitation

Outcome Measures

Primary Outcome Measures

Quadriceps muscle strength assessment [Baseline, 4 months, 6 months, 2 months after TKA, 6 months after TKA]
Hand-held dynamometer microFET2 (Hoggan Scientific, Salt Lake City UT, USA) will be used to assess lower limb strength and power. Assessment of isometric muscle strength and power will be performed with the participants in a seated position to assess knee extensors and knee flexors. All tests will involve maximal voluntary isometric contractions. Both limbs will be assessed to record side-to-side difference. Two trials were recorded for each muscle group.
Handgrip strength [Baseline, 4 months, 6 months, 2 months after TKA, 6 months after TKA]
The handgrip dynamometer will be used to test for the patients' handgrip strength. The handgrip dynamometer is an instrument measuring patients' maximum isometric strength of the hand and forearm muscles. The handle of the dynamometer will be adjusted as the finger is at 90 o whilst the dynamometer is being held. The measurement will be repeated three times and the average calculated for the dominant hand (Hand dominance will be determined by observing the patient's writing hand when signing the informed consent).

Secondary Outcome Measures

Baseline, 4 months, 6 months, 2 months after TKA, 6 months after TKA [Baseline, 4 months, 6 months, 2 months after TKA, 6 months after TKA]
The 10-meter timed walking test is a well-established test to assess gait speed. However, due to space limitations and the exhaustive nature of the test for patients with OA, the 6-meter test has been documented to be a valid and reliable substitute. Patients will be asked to walk a straight line of 6 meters where the time taken to complete the distance will be measured. (<7.5 seconds is normal).
Chair stand test [Baseline, 4 months, 6 months, 2 months after TKA, 6 months after TKA]
The chair stand test is a reliable test for assessment for low limb strength in patients. Patients will be asked to sit on a solid chair with arms on shoulders and feet with shoulder width apart. They will be instructed to do 1-2 repetitions to become familiar with the test, and perform as many reputations as they can in 30 seconds.
Dual Energy X-ray Absorptiometry (DXA) [Baseline, 2 months after TKA]
The radiation for one session (20 minutes) for sarcopenia assessment is less than 25µSv, which is within the safe range. After every DXA scan, two copies will be printed that show the patients' body composition, bone mineral density, fat percentage, body mass index, and most importantly for this study, lean muscle mass.
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) [Baseline, 4 months, 6 months, 2 months after TKA, 6 months after TKA]
It is a questionnaire that measures a patient's pain, stiffness and physical function and can be summed up into a score out of 96. A high score indicates a more disabled participant .
Knee Society Score (KSS) [Baseline, 4 months, 6 months, 2 months after TKA, 6 months after TKA]
Assesses a patient's pain and functionality based on a series of questions interviewed by a clinician. The validated questionnaire combines the objective physician-derived component with a subjective patient-derived component which evaluates pain, functionality, satisfaction, and fulfilment of expectations. The results will be calculating the total score with 100 being the highest and 0 the lowest .
Short-Form 12 (SF-12) [Baseline, 4 months, 6 months, 2 months after TKA, 6 months after TKA]
12 questions to measure a patient's functional health and well-being from a patient's point of view. It is a reliable and validated measure that summarises the patients' physical and mental health
International Physical Activity Questionnaire (IPAQ) [Baseline, 4 months, 6 months, 2 months after TKA, 6 months after TKA]
Assesses and monitors a patient's physical activity and inactivity level. This instrument sums up a patient's activity level per week into three categories, Category 1 Inactivity, category 2 minimally active and category 3 HEPA active
Nutritional intake questionnaire [Baseline]
Evaluation of habitual dietary intake will be based on retrospective means of assessment for the past twelve months. A Food Frequency Questionnaire (FFQ) previously validated with data obtained in the Hong Kong Adult Dietary Survey in 1995 as described previously will be used(Appendix 7). Daily dietary intake of Vitamin D and calcium will be evaluated by the Food Processor Nutrition Analysis and Fitness software version 7.9 (Esha Research, Salem, USA), with incorporation of local food composition based on food composition table from China

Eligibility Criteria

Criteria

Ages Eligible for Study:

70 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

(1)Male and female patients aged over 70 with end-stage knee OA (2) Patient has been scheduled for TKR at Prince of Wales Hospital (3) Walk unaided for 6 metres (4) Able to comply with the assessments and has given oral and written consent (5) Patients with vitamin D insufficiency and deficiency at the baseline measurement (25(OH)D <30 ng/mL)

Exclusion Criteria:

(1) Patients with connective tissue disorders or myositis condition (2) History of any Hip & Knee surgery (3) Patients with malnutrition assessed by Mini-Nutritional assessment. (4) Patients with acute immobility (i.e., post hip fracture or post-acute hospital admission) (5) Patient scheduled for TKR within 6 months (6) Patients already taking vitamin D supplements (7) Patients with a known contraindication to vitamin D treatment (such as allergy) (8) Patients who have renal impairment with glomerular filtration rate (eGFR) < 30 ml/minute