To Evaluate the Efficacy and Safety of Amorphous Calcium Carbonate in RA Patient With Osteopenia or Osteoporosis

A Randomized, Double-blind, Active-controlled Study to Evaluate the Effects of Amorphous Calcium Carbonate in Rheumatoid Arthritis Patients With Osteopenia or Osteoporosis

DensityTM, an amorphous calcium carbonate (ACC) imported by Universal Integrated Corporation, is tried to demonstrate its efficacy and safety in rheumatoid arthritis patient with osteopenia or osteoporosis, compared to crystalized calcium carbonate (CCC).

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis; Osteopenia or Osteoporosis
• Intervention / Treatment: Dietary supplement: DENSITY™ (Amorphous calcium carbonate, ACC); Dietary supplement: Crystalized calcium carbonate (CCC)

Detailed Description

This is a randomized, double-blind, active-controlled study to evaluate the efficacy and safety of amorphous calcium carbonate in rheumatoid arthritis patients with osteopenia or osteoporosis, compared to crystalized calcium carbonate.

A total of 180 subjects will be enrolled into this study. Eligible subjects will be randomized to receive amorphous calcium carbonate (ACC group) or crystalized calcium carbonate (CCC group) with 1:1 allocation. Randomization will be stratified by the use of biologics. The study product, 2 tablets (400mg calcium element), will be taken twice daily approximately 30 minutes after breakfast and dinner during 12-month treatment period. Additional 600 IU vitamin D3 will be also received with investigational product after breakfast.

The study will consist of 7 clinical visits. Subjects will come to the clinics at Visit 1 (screening visit), Visit 2 (randomization, regimen start), Visit 3 to 6 (follow-up visits), and Visit 7 (post-treatment follow-up visits) according to the pre-defined schedule.

The DXA score, and BTM (P1NP, CTX) from fasting serum samples, and FRAX score will be collected. The treatment-emergent adverse events for safety endpoints will be also recorded.

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Der-Yuan Chen, Doctor; Phone Number: 2031 886-4-22052121; Email: dychen1957@gmail.com

Study Locations

• Taiwan
  • Taichung, Taiwan, 404327
    • Recruiting
    • China Medical University Hospital
    • Contact: Der-Yuan Chen, Doctor; Phone Number: 2031 886-4-22052121; Email: dychen1957@gmail.com
  • Taipei, Taiwan, 112201
    • Recruiting
    • Taipei Veterans General Hospital
    • Contact: Wei-Sheng Chen, Doctor; Phone Number: 3366 886-2-28712121; Email: weisheng0112@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men or women ≧45 years of age.
2. Diagnosis of rheumatoid arthritis according to 2010 American College of Rheumatology Guideline (ACR Guideline), with severe osteopenia or osteoporosis.
3. With a DAS28 (Disease Activity Score 28) score ranged from 2.6 to 5.1 at screening visit.
4. With a documented DXA score ≦-2.0 at the lumbar spine or total hip and without compression fracture within the 3 months prior to screening visit.
5. With a FRAX score at least medium risk (major osteoporotic fracture 10-19%, hip fracture 1-3%) at screening visit.
6. Willingness to limit additional vitamin D3 intake to 600 IU per day during the study period.
7. Ability to complete the entire procedure and to comply with study instructions.
8. Will provide completed and signed written informed consents.

Exclusion Criteria:

1. History of or current diseases that may interfere serum calcium, such as hypocalcemia, hypercalcemia, hyperparathyroidism, hypoparathyroidism, hyperthyroidism or hypothyroidism, or other metabolic bone disease, from any cause within 1 year prior to screening.
2. Chronic kidney disease with receiving peritoneal dialysis or hemodialysis
3. Known hypersensitivity to any component of the study product.
4. Current treatment with any anti-osteoporotic drug (i.e. bisphosphonates, Denosumab (Prolia), teriparatide (Forteo), Romosozumab (Evenity), Raloxifene (Evista), etc.).
5. Any previous or ongoing clinically significant illness that may interfere with the study conduct, as judged by the investigator.
6. Participation in any other investigational study within 30 days prior to receiving study medication.
7. Any condition that in the opinion of the investigator would jeopardize the evaluation of efficacy or safety.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: amorphous calcium carbonate (ACC group); oral use, 2 ACC tablets (1000 mg / tablet, 200 mg calcium element / tablet) twice daily given after breakfast and dinner.	Dietary supplement: DENSITY™ (Amorphous calcium carbonate, ACC); Dosage form: tablet; Dose(s): 1000 mg /tablet, comprising 500 mg amorphous calcium carbonate per tablet (calcium element 200mg); Dosing schedule: The usual dose for oral use is 2 ACC tablets (400 mg calcium element) twice daily given after breakfast and dinner.
Active Comparator: crystalized calcium carbonate (CCC group); oral use, 2 CCC tablets (1000 mg / tablet, 200 mg calcium element / tablet) twice daily given after breakfast and dinner.	Dietary supplement: Crystalized calcium carbonate (CCC); Dosage form: tablet; Dose(s): 1000 mg /tablet, comprising 500 mg crystalized calcium carbonate per tablet (calcium element 200mg); Dosing schedule: The usual dose for oral use is 2 CCC tablets (400 mg calcium element) twice daily given after breakfast and dinner.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline in bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA) in lumbar spine and total hip at Month 13	The BMD and the corresponding change from baseline will be summarized with descriptive statistics and the 95% CI by study groups. The difference in mean change from baseline in BMD between study groups will be analyzed by two sample t test. Additionally, the intra-group difference will be analyzed by paired t test.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage change from baseline in bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA) in lumbar spine and total hip at Month 13	The percentage change from baseline in BMD measured by DXA in lumbar spine and total hip at Month 13 will be summarized with descriptive statistics and the 95% CI by study groups. The difference in percentage change from baseline in BMD between study groups will be analyzed by two sample t test.	12 months
Responder number and rate in bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA) in lumbar spine and total hip at Month 13	The responder is defined as 20% reduction in DXA score from the baseline. The responder will be presented as count and percentage in frequency table, and the 95% exact (Clopper-Pearson) CI will be provided as well by study group. Fisher's exact test will be used for the comparison between study groups.	12 months
FRAX score (Fracture Risk Assessment Tool) change from baseline at Visit 1, 4, and 6	The FRAX score and the corresponding change from baseline at Visit 1, 4, and 6 will be summarized with descriptive statistics and the 95% CI by study groups. The difference in mean change from baseline in FRAX score between study groups will be analyzed by two sample t test. Additionally, the intra-group difference will be analyzed by paired t test.	12 months
Bone turnover markers (BTM) change from baseline level 5.1 P1NP (total procollagen type 1 N-terminal propeptide) 5.2 CTX (C-terminal telopeptide of type 1 collagen)	The bone turnover markers (BTM) includes P1NP (total procollagen type 1 N-terminal propeptide) and CTX (C-terminal telopeptide of type 1 collagen). For the bone turnover markers (BTM), the descriptive summary of original values and the change from baseline will be provided by study groups. Two sample t test will be used for the comparison of study groups in change from baseline be. Additionally, the intra-group comparison will be analyzed by paired t test.	12 months

Collaborators and Investigators

• Sponsor: China Medical University Hospital
• Investigators: Principal Investigator: Der-Yuan Chen, Doctor, Rheumatology and Immunology Center; Principal Investigator: Wei-Sheng Chen, Doctor, Division of Allergy, immunology and Rheumatology

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2022
• Primary Completion (Anticipated): January 31, 2024
• Study Completion (Anticipated): January 31, 2024

Study Registration Dates

• First Submitted: June 15, 2022
• First Submitted That Met QC Criteria: June 29, 2022
• First Posted (Actual): July 5, 2022

Study Record Updates

• Last Update Posted (Actual): July 5, 2022
• Last Update Submitted That Met QC Criteria: June 29, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Bone Diseases; Arthritis; Arthritis, Rheumatoid; Osteoporosis; Bone Diseases, Metabolic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Antacids; Calcium; Calcium, Dietary; Calcium Carbonate
• Other Study ID Numbers: CMUH111-REC2-014

Drug and device information, study documents

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