Clinical trial NCT04739592: A Study of Alendronate Sodium Vitamin D3 Tablets on Knee Osteoarthritis
Official title: The Effect of Alendronate Sodium Vitamin D3 Tablets on Knee Joint Structure and Knee Osteoarthritis Pain: A Multi-center, Randomized, Double-blind, Controlled Study.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Knee Osteoarthritis
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: CSPC Ouyi Pharmaceutical Co., Ltd.
First posted: 2021-02-04
Enrollment: 60
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the effect of alendronate sodium vitamin D3 tablets compared with placebo on the improvement of joint structure and joint pain in participants with knee osteoarthritis. The treatment period of this study is one year and followed-up period is 2 years. The results of knee joint MRI will be evaluated by using the WORMS score.

Detailed description: This is a multi-center, randomized, double-blind, placebo-controlled study This study is planned to commence after obtaining Ethics Committee approval. participants will be randomised to a one-year course of alendronate sodium vitamin D3 tablets or placebo. 1:1 double blinded randomisation will be undertaken. This study plans to enroll 60 participants and will be carried out in three domestic centers (Peking Union Medical College Hospital, Zhongshan Hospital and The Third Affiliated Hospital of Southern Medical University) with a follow-up period of 2 years.

As the main goal of this exploratory study is to evaluate the effect of alendronate sodium vitamin D3 tablets compared with placebo on the improvement of joint structure and joint pain in participants with knee osteoarthritis. The primary outcome measure is WORMS score of knee joint MRI at 6 months and 12 months.

Eligibility criteria: Inclusion Criteria:

1. Patients with significant knee pain (pain score≥40mm on the 100mmVAS scale);
2. Male or female patients, between 50-75 years old;
3. MRI suggests bone marrow edema-like lesions;
4. Knee osteoarthritis (in accordance with the diagnostic criteria of American College of Rheumatology (ACR) and Chinese Orthopaedic Association);
5. Kellgren-Lawrence gradingⅠorⅡin X-ray;

Exclusion Criteria:

1. Other forms of active arthritis (such as rheumatoid arthritis or other inflammatory arthritis);
2. Taken non-steroidal anti-inflammatory drugs and central analgesics (such as opioids) within two weeks；
3. Liver function ALT or AST is 1.5 times the upper limit of normal； creatinine clearance \<35ml/min；
4. Pregnancy or suckling;
5. Serious heart disease, endocrine, digestive, mental, nervous system diseases or cancer;
6. Active ulcers and a history of upper gastrointestinal bleeding;
7. Esophageal motility disorders, such as esophageal tardiness or stenosis;
8. Renal dysfunction or osteomalacia;
9. Tobacco addiction (mean 10 cigarettes per day or more) or/and alcohol addiction (mean 50ml per day or more);
10. Fresh fracture in the last six months;
11. Serious illnesses and life expectancy\<2 years;
12. Allergic to study drugs;
13. Used any study drug or device within 30 days before randomization or within the drug half-life (whichever is longer);
14. Failure to take medication as required;
15. Replacement surgery in the near future;
16. Contraindications to MRI scans (e.g. implanted pacemakers, metal sutures, shrapnel or iron filings in the eyes, claustrophobia, knees too large to use coils);
17. Sensitive to or unsuitable for X-ray exposure (e.g. aplastic anemia, etc);
18. Poor dental health or dental surgery in the near future.

Primary outcomes:
measure: WORMS score of knee joint MRI
timeFrame: The sixth month
measure: WORMS score of knee joint MRI
timeFrame: The 12th month
Secondary outcomes:
measure: WORMS score of knee joint MRI
timeFrame: The 24th month
measure: Pain intensity and symptom record
timeFrame: The second week
measure: Pain intensity and symptom record
timeFrame: The 4th week
measure: Pain intensity and symptom record
timeFrame: The 8th week
measure: Pain intensity and symptom record
timeFrame: The 12th week
measure: Quality of life (the MOS item short from health survey,SF-36 )
timeFrame: The third month
measure: Quality of life (the MOS item short from health survey,SF-36 )
timeFrame: The sixth month
measure: Quality of life (the MOS item short from health survey,SF-36 )
timeFrame: The 12th month
measure: bone density (lumbar spine, hip joint and knee joint)
timeFrame: The 12th month
measure: bone density (lumbar spine, hip joint and knee joint)
timeFrame: The 24th month
measure: Risk of knee replacement
timeFrame: The 12th month
measure: Risk of knee replacement
timeFrame: The 24th month
measure: Kellgren & Lawrence(KL) grading Score
timeFrame: The 12th month
measure: Kellgren & Lawrence(KL) grading Score
timeFrame: The 24th month
measure: Serum IL-6, TNF-a, erythrocyte sedimentation rate, C-reactive protein
timeFrame: The third month
measure: Serum IL-6, TNF-a, erythrocyte sedimentation rate, C-reactive protein
timeFrame: The sixth month
measure: Serum IL-6, TNF-a, erythrocyte sedimentation rate, C-reactive protein
timeFrame: The 12th month
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Southern Medical University
city: Shanghai
country: China
facility: Zhongshan Hospital
Study officials:
References:
citation: Peng HM, Weng XS, Li Y, Feng B, Qian W, Cai DZ, Zhao C, Yao ZJ, Yang Y, Zhang C, Wan S. Effect of alendronate sodium plus vitamin D3 tablets on knee joint structure and osteoarthritis pain: a multi-center, randomized, double-blind, placebo-controlled study protocol. BMC Musculoskelet Disord. 2022 Jun 17;23(1):584. doi: 10.1186/s12891-022-05521-4.