A Prospective, Randomized, Parallel, Double-blind, Active Controlled Pilot Study Comparing the Effect of Amorphous Calcium Carbonate (ACC) Versus Placebo on Functional Outcome and Radiographic Healing Time of Distal Radius Fractures
A Prospective, Randomized, Parallel, Double-blind, Active Controlled Pilot Study Comparing the Effect of Amorphous Calcium Carbonate (ACC) Versus Placebo on Functional Outcome and Radiographic Healing Time of Distal Radius Fractures
Amorphical has a strong basis to believe that the Amorphous Calcium Carbonate (ACC) product has an effect on active mineralization during bone remodelling hence, it has a potential to accelerate fracture healing process. The active mineralization can most probably be attributed to the mineral component of this substance.
The distal radius fracture was chosen as the model to test the effects of ACC treatment because it includes both trabecular and cortical bone, is accessible for radiographs, has little soft tissue that can distort the radiograph, and is amenable to multiple functional endpoints.
Primary objective:
To assess the efficacy of treatment with calcium from ACC compared to placebo on radiographic healing time in subjects with distal radius fractures.
Secondary objectives:
Eligible subjects will be treated as follows:
Fifty (50) subjects will be randomly assigned to one of two groups (N=25). Subjects in the treatment group will receive amorphous calcium carbonate (ACC) and those in the active control group will receive placebo. Both formulations will be supplemented with vitamin D.
Safety parameters will be evaluated throughout the trial.
Subjects admitting to Barzilai medical center hand clinic following a new distal radius fracture will be routinely evaluated. Subjects who were initially treated according to current practice of fracture management, (i.e.; radiographic evaluation and fracture fixation by splint in plaster of Paris), who are not candidates for surgery and who are aimed for non-invasive treatment, will be considered candidates for the trial and be invited to the clinical research center (CRC) for screening.
Screening (Day -7) - Subjects will sign an informed consent form (ICF). Chemistry and hematology tests will be performed: sodium, potassium, hemoglobin, sedimentation rate, leukocytes calcium (total, albumin-corrected), phosphate, alkaline phosphatase, creatinine, and albumin. Also, serum parathyroid hormone (PTH), 25-hydroxyvitamin D, and thyroid-stimulating hormone (TSH) will be tested. Urinary excretion of calcium and creatinine will be measured. General health will be examined by medical history and physical examinations. Eligible subjects, complying with all inclusion criteria and none of the exclusion criteria will be enrolled to the study.
Subjects will be informed by phone or on site whether they are eligible to enter the study.
Visit 1 - 1 week from fracture - (Day 0 (-7/+1)) - Eligible subjects will be invited to the CRC. A fixture device will be applied to the cast to ensure consistence imaging. X-ray will be performed to exclude loss of reduction. Subjects will randomly receive packs of tablets (a total of 180 tablets, 42 day supply + 12 spare tablets), either tablets containing 200 mg elemental calcium from ACC or placebo (300 mg StarLac (starch cellulose and lactose blend)). Subjects who will arrive prior to day 0 will be instructed to begin the treatment exactly 7 days from the fracture event. Subjects will be instructed to take 4 tablets a day for the first 6 weeks (days 0-42), 2 tablets in the morning and 2 tablets in the evening, after a meal (i.e., the study group will consume a total of 800mg elemental calcium per day). To minimize the risks for calcium related side effects, subjects who take calcium regularly, will be instructed to discontinue their calcium supplements intake throughout the trial.
Visit 2 - 4 weeks from fracture - (Day 21±1) - Pre-dose serum calcium concentrations will be measured. The cast will be removed and controlled entero posterior and lateral x-ray will be taken. Functional assessment (pain-free grip and force plate) measurement and questionnaires (VAS, DASH) will be performed. The wrist will be fixed using an adjustable brace. Subjects will be asked about any side effects or adverse events (AEs) that may have occurred. Subjects will complete the TSQM questionnaire with the representative of the CRC.
Visit 3 - 7 weeks from fracture - (Day 42±1) - Pre-dose serum calcium concentration and urinary calcium and creatinine concentrations will be measured. Controlled entero posterior and lateral x-ray will be taken without the brace. Functional assessment (pain-free grip and force plate) measurement and questionnaires (VAS, DASH) will be performed. Subjects will receive additional packs of capsules, (a total of 180 capsules, 42 day supply + 12 spare capsules) with the same formulation received in day 0: either tablets containing 200 mg elemental calcium from ACC or placebo (300 mg StarLac (starch cellulose and lactose blend)). Subjects will be instructed to take 4 tablets a day for the next 6 weeks (days 42-84) 2 tablets in the morning and 2 tablets in the evening, after a meal (i.e., the study group will consume a total of 800mg elemental calcium per day). To minimize the risks for calcium related side effects, subjects who take calcium regularly, will be instructed to discontinue their calcium supplements intake throughout the trial. Subjects who did not show radiographic healing in the x-ray will be invited for an additional radiographic assessment on day 56.
Visit 4 - 9 weeks from fracture - (Day 56±1)* - Controlled entero posterior and lateral x-ray will be taken without the brace. Functional assessment (pain-free grip and force plate) measurement and questionnaires (VAS, DASH) will be performed. Subjects will be asked about any side effects or AEs that may have occurred. Subjects that did not show radiographic healing in the x-ray will be invited for an additional radiographic assessment on day 70.
Visit 5 - 11 weeks from fracture - (Day 70±1)* - Controlled entero posterior and lateral x-ray will be taken without the brace. Functional assessment (pain-free grip and force plate) measurement and questionnaires (VAS, DASH) will be performed. Subjects will be asked about any side effects or AEs that may have occurred.
Visit 6 - 13 weeks from fracture - (Day 84±1) - Pre-dose serum calcium and 25-hydroxyvitamin D concentration and urinary calcium and creatinine concentrations will be measured. Controlled entero posterior and lateral x-ray will be taken. Functional assessment (pain-free grip and force plate) measurement and questionnaires (VAS, DASH) will be performed. Subjects will be asked about any side effects or AEs that may have occurred. Subjects will complete the TSQM questionnaire with the representative of the CRC. The subjects will be instructed to discontinue the study treatment administration. Subjects that discontinued their regularly calcium supplementation at the beginning of the study will be instructed to continue their regular dose intake.
Visit 7 - 24 weeks from fracture - (Day 161±1) - Serum calcium concentration and urinary calcium and creatinine concentrations will be measured. Functional assessment (pain-free grip and force plate) measurement and questionnaires (VAS, DASH) will be performed. Subjects will be asked about any side effects or AEs that may have occurred.
* Only for subjects that did not show radiographic healing on x-ray performed on previous visit.
Inclusion Criteria:
Exclusion Criteria: