A Study of Alendronate Sodium Vitamin D3 Tablets on Knee Osteoarthritis

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Effect of Alendronate Sodium Vitamin D3 Tablets on Knee Joint Structure and Knee Osteoarthritis Pain: A Multi-center, Randomized, Double-blind, Controlled Study.

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Drug: alendronate sodium vitamin D3 tablets
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with significant knee pain (pain score≥40mm on the 100mmVAS scale); Male or female patients, between 50-75 years old; MRI suggests bone marrow edema-like lesions; Knee osteoarthritis (in accordance with the diagnostic criteria of American College of Rheumatology (ACR) and Chinese Orthopaedic Association); Kellgren-Lawrence gradingⅠorⅡin X-ray; Exclusion Criteria: Other forms of active arthritis (such as rheumatoid arthritis or other inflammatory arthritis); Taken non-steroidal anti-inflammatory drugs and central analgesics (such as opioids) within two weeks； Liver function ALT or AST is 1.5 times the upper limit of normal； creatinine clearance <35ml/min； Pregnancy or suckling; Serious heart disease, endocrine, digestive, mental, nervous system diseases or cancer; Active ulcers and a history of upper gastrointestinal bleeding; Esophageal motility disorders, such as esophageal tardiness or stenosis; Renal dysfunction or osteomalacia; Tobacco addiction (mean 10 cigarettes per day or more) or/and alcohol addiction (mean 50ml per day or more); Fresh fracture in the last six months; Serious illnesses and life expectancy<2 years; Allergic to study drugs; Used any study drug or device within 30 days before randomization or within the drug half-life (whichever is longer); Failure to take medication as required; Replacement surgery in the near future; Contraindications to MRI scans (e.g. implanted pacemakers, metal sutures, shrapnel or iron filings in the eyes, claustrophobia, knees too large to use coils); Sensitive to or unsuitable for X-ray exposure (e.g. aplastic anemia, etc); Poor dental health or dental surgery in the near future.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: alendronate sodium vitamin D3 tablets<br>participants will receive alendronate sodium vitamin D3 tablets once per week for one year. | Drug: alendronate sodium vitamin D3 tablets<br>* once per week for one year<br>|
| Placebo Comparator: placebo<br>participants will receive a placebo tablet once per week for one year. | Drug: Placebo<br>* once per week for one year<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WORMS score of knee joint MRI | WORM score of participants at the sixth month after enrollment | The sixth month | 
| WORMS score of knee joint MRI | WORM score of participants at the 12th month after enrollment | The 12th month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WORMS score of knee joint MRI | WORM score of patients at the 24th month after enrollment | The 24th month | 
| Pain intensity and symptom record | Pain intensity and symptom record of patients at the second week after enrollment | The second week | 
| Pain intensity and symptom record | Pain intensity and symptom record of patients at the 4th week after enrollment | The 4th week | 
| Pain intensity and symptom record | Pain intensity and symptom record of patients at the 8th week after enrollment | The 8th week | 
| Pain intensity and symptom record | Pain intensity and symptom record of patients at the 12th week after enrollment | The 12th week | 
| Quality of life (the MOS item short from health survey,SF-36 ) | SF-36 scale of patients at the third month after enrollment | The third month | 
| Quality of life (the MOS item short from health survey,SF-36 ) | SF-36 scale of patients at the sixth month after enrollment. The score is calculated from eight dimensions, with the higher the final score the better | The sixth month | 
| Quality of life (the MOS item short from health survey,SF-36 ) | SF-36 scale of patients at the 12th month after enrollment. The score is calculated from eight dimensions, with the higher the final score the better | The 12th month | 
| bone density (lumbar spine, hip joint and knee joint) | bone density of patients at the 12th month after enrollment | The 12th month | 
| bone density (lumbar spine, hip joint and knee joint) | bone density of patients at the 24th month after enrollment | The 24th month | 
| Risk of knee replacement | Risk of knee replacement of patients at the 12th month after enrollment | The 12th month | 
| Risk of knee replacement | Risk of knee replacement of patients at the 24th month after enrollment | The 24th month | 
| Kellgren & Lawrence(KL) grading Score | KL-grading Score of patients at the 12th month after enrollment, 0 to Ⅳ, higher scores mean a worse outcome | The 12th month | 
| Kellgren & Lawrence(KL) grading Score | KL-grading Score of patients at the 12th month after enrollment, 0 to Ⅳ, higher scores mean a worse outcome | The 24th month | 
| Serum IL-6, TNF-a, erythrocyte sedimentation rate, C-reactive protein | Serum inflammatory factor of patients at the third month after enrollment, IL-6 and TNF-a were measured in pg/ml,erythrocyte sedimentation rate was measured in mm/h, C-reactive protein was measured in mg/dL. | The third month | 
| Serum IL-6, TNF-a, erythrocyte sedimentation rate, C-reactive protein | Serum inflammatory factor of patients at the sixth month after enrollment, IL-6 and TNF-a were measured in pg/ml,erythrocyte sedimentation rate was measured in mm/h, C-reactive protein was measured in mg/dL. | The sixth month | 
| Serum IL-6, TNF-a, erythrocyte sedimentation rate, C-reactive protein | Serum inflammatory factor of patients at the 12th month after enrollment, IL-6 and TNF-a were measured in pg/ml,erythrocyte sedimentation rate was measured in mm/h, C-reactive protein was measured in mg/dL. | The 12th month |