A Study of Alendronate Sodium Vitamin D3 Tablets on Knee Osteoarthritis

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

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.

Study Overview

• Status: Recruiting
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Drug: alendronate sodium vitamin D3 tablets; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Huiming Peng; Phone Number: 13601276089; Email: penghuiming@139.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking Union Medical College Hospital
    • Contact: Huiming Peng; Phone Number: 1; Email: penghuiming@139.com
  • Guangzhou, China
    • Recruiting
    • The Third Affiliated Hospital of Southern Medical University
    • Contact: Chang Zhao; Email: zhaochang81@126.com
  • Shanghai, China
    • Recruiting
    • Zhongshan Hospital
    • Contact: Yi Yang; Email: dlyangyi@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: alendronate sodium vitamin D3 tablets; participants will receive alendronate sodium vitamin D3 tablets once per week for one year.	Drug: alendronate sodium vitamin D3 tablets; once per week for one year
PLACEBO_COMPARATOR: placebo; participants will receive a placebo tablet once per week for one year.	Drug: Placebo; once per week for one year

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: CSPC Ouyi Pharmaceutical Co., Ltd.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 7, 2021
• Primary Completion (ANTICIPATED): July 1, 2023
• Study Completion (ANTICIPATED): July 1, 2024

Study Registration Dates

• First Submitted: January 13, 2021
• First Submitted That Met QC Criteria: February 3, 2021
• First Posted (ACTUAL): February 4, 2021

Study Record Updates

• Last Update Posted (ACTUAL): April 22, 2022
• Last Update Submitted That Met QC Criteria: April 21, 2022
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Alendronate
• Other Study ID Numbers: Peking UMCH

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No