Trial record 5 of 700 for:    Open Studies | dietary calcium

A Study Comparing Amorphous Calcium Carbonate (ACC) Versus Crystalline Calcium CCS) in Hypoparathyroidism Patients (AMCS009)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified March 2013 by Amorphical Ltd.
Sponsor:
Information provided by (Responsible Party):
Amorphical Ltd.
ClinicalTrials.gov Identifier:
NCT01815021
First received: March 7, 2013
Last updated: March 19, 2013
Last verified: March 2013
  Purpose

Primary objective:

Phase I Proof of concept: treatment with smaller doses of elemental calcium from ACC compared to CCS can maintain target serum calcium (corrected for albumin) values (7.0-10.0 mg/dL).

Phase II To test the hypothesis that treatment with smaller doses of elemental calcium from ACC compared to CCS can maintain target serum calcium (corrected for albumin) values (7.0-10.0 mg/dL).

Secondary objectives:

Phase I

  • ACC dose selection - to confirm the conversion factor of ACC from CCS
  • To determine the effect of food on ACC absorption

Phase II

  • To test the hypothesis that treatment with smaller doses of elemental calcium from ACC compared to CCS will not cause an increase in hypercalciuria in patients with hypoparathyroidism
  • To test the hypothesis that smaller doses of elemental calcium from ACC can reduce the side effects related with high calcium consumption.

Amorphical has a strong basis to believe that the ACC product is better absorbed compared to the commercially available CCS products and therefore, can maintain desirable target albumin corrected calcium values in serum (CA) with smaller doses of elemental calcium from ACC. As results, the burden of taking high doses of calcium supplementation along with the side effects of the standard therapy (gastrointestinal discomfort and hypercalciuria) will be reduced.

Testing serum CA and urine calcium values in subjects with hypoparathyroidism may provide a straightforward method to test this hypothesis.

The study is designed to be conducted with extra precaution in order to avoid disturbing the fragile balance between CA levels in serum and calcium levels urine. The crossover design of phase II of the study allows a more accurate and reliable comparison of results attributable to the specific treatment within the same individual. In addition, the subjects will continue consuming all their routine medication throughout the trial. The subjects in the control arm will consume their routine calcium supplement doses thus, will be treated with a standard of care.


Condition Intervention Phase
Hypoparathyroidism
Dietary Supplement: amorphous calcium carbonate
Dietary Supplement: crystalline calcium supplements
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Two Phase, Adaptive Then Crossover Open-label, Study Comparing Amorphous Calcium Carbonate (ACC) Supplement Versus Commercially Available Crystalline Calcium Supplements (CCS) in the Management of Primary Hypoparathyroidism.

Resource links provided by NLM:


Further study details as provided by Amorphical Ltd.:

Primary Outcome Measures:
  • Calcium (albumin-corrected) serum level - composite value based on multiple measurements [ Time Frame: Blood tests will be performed for each subject in each CRC visit from day 0 and onward: Phase I: Day 0, 3, 7, 10, 14, 21, 28. Phase II: Day 0, 3, 7, 10, 14, 21, 35, 38, 42, 45, 49, 56, 70. ] [ Designated as safety issue: Yes ]

    The initial assessment of hypocal¬cemia is usually based on the measurement of serum total calcium corrected for albumin concentration. Normal CA values range from 8.5 to 10.2 mg/dL. In subjects with hypoparathyroidism, the desired target CA values are 7.0-10.0 mg/dL.

    The relationship between total serum calcium and albumin is defined by the following rule: the serum total calcium concentration falls by 0.8 mg/dL for every 1-g/dL fall in serum albumin concentration. This rule assumes that normal albumin equals 4.0 g/dL and normal calcium is 10.0 mg/dL.

    Calculation: Calcium (corrected, mmol/L) = Calcium (measured, mmol/L) + {(40 - albumin(g/L)) x 0.02}



Secondary Outcome Measures:
  • Urine calcium level - 24h urine collection [ Time Frame: Phase I: Termination of study (Day 28) ] [ Designated as safety issue: Yes ]

    For a 24-hour urine collection, all of the urine over a 24-hour time period must be collected. The urine sample must include the last urine, 24 hours after starting the collection.

    Urine calcium level > 300 mg/24 hours or > 4 mg/kg of weight/24 hours is considered as hypercalciuria.


  • Phosphorous serum level - composite value based on multiple measurements [ Time Frame: Blood tests will be performed for each subject in each CRC visit from day 0 and onward: Phase I: Day 0, 3, 7, 10, 14, 21, 28. Phase II: Day 0, 3, 7, 10, 14, 21, 35, 38, 42, 45, 49, 56, 70 ] [ Designated as safety issue: Yes ]
    The serum phosphorus test measures the amount of phosphate in the blood. Normal values range from 2.4 - 4.1 mg/dL

  • Urine calcium level - 24h urine collection [ Time Frame: Phase II: Day 35 ] [ Designated as safety issue: Yes ]

    For a 24-hour urine collection, all of the urine over a 24-hour time period must be collected. The urine sample must include the last urine, 24 hours after starting the collection.

    Urine calcium level > 300 mg/24 hours or > 4 mg/kg of weight/24 hours is considered as hypercalciuria.


  • Urine calcium level - 24h urine collection [ Time Frame: Phase II: termination of study (Day 70) ] [ Designated as safety issue: Yes ]

    For a 24-hour urine collection, all of the urine over a 24-hour time period must be collected. The urine sample must include the last urine, 24 hours after starting the collection.

    Urine calcium level > 300 mg/24 hours or > 4 mg/kg of weight/24 hours is considered as hypercalciuria.


  • Assessment of symptoms and signs related with hypocalcemia - composite value based on multiple measurements [ Time Frame: Phase I: Day 7, 14, 21, 28 Phase II: Day 7, 14, 21, 35, 42, 49, 56, 70 ] [ Designated as safety issue: No ]
    At each visit to the CRC, subjects will be asked to answer questions for the presence of symptoms and signs related with hypocalcemia (tetany, facial grimacing, paresthesias, muscle aches, arrhythmia, depression).

  • Urine creatinine level - 24h urine collection [ Time Frame: Phase I: Termination of study (Day 28) ] [ Designated as safety issue: Yes ]

    For a 24-hour urine collection, all of the urine over a 24-hour time period must be collected. The urine sample must include the last urine, 24 hours after starting the collection.

    A creatinine clearance test is done on a sample of urine collected over 24 hours. It is used to determine glomerular filtration rate, which helps to measure how well the kidney functions. The normal adult urine calcium/creatinine ratio is <220 mg/g


  • Urine creatinine level - 24h urine collection [ Time Frame: Phase II: Day 35 ] [ Designated as safety issue: Yes ]

    For a 24-hour urine collection, all of the urine over a 24-hour time period must be collected. The urine sample must include the last urine, 24 hours after starting the collection.

    A creatinine clearance test is done on a sample of urine collected over 24 hours. It is used to determine glomerular filtration rate, which helps to measure how well the kidney functions. The normal adult urine calcium/creatinine ratio is <220 mg/g


  • Urine creatinine level - 24h urine collection [ Time Frame: Phase II: termination of study (Day 70) ] [ Designated as safety issue: Yes ]

    For a 24-hour urine collection, all of the urine over a 24-hour time period must be collected. The urine sample must include the last urine, 24 hours after starting the collection.

    A creatinine clearance test is done on a sample of urine collected over 24 hours. It is used to determine glomerular filtration rate, which helps to measure how well the kidney functions. The normal adult urine calcium/creatinine ratio is <220 mg/g


  • Urine phosphorus level - 24h urine collection [ Time Frame: Phase I: Termination of study (Day 28) ] [ Designated as safety issue: Yes ]

    The phosphate urine test measures the amount of phosphate in a sample of urine collected over 24 hours (24-hour urine test). Phosphate is a charged ion that contains the mineral phosphorus.

    Results of a test to measure phosphate in urine are seldom useful on their own. They should always be interpreted along with the results of other tests. Calcium and phosphate levels are often measured at the same time.


  • Urine phosphorus level - 24h urine collection [ Time Frame: Phase II: Day 35 ] [ Designated as safety issue: Yes ]

    The phosphate urine test measures the amount of phosphate in a sample of urine collected over 24 hours (24-hour urine test). Phosphate is a charged ion that contains the mineral phosphorus.

    Results of a test to measure phosphate in urine are seldom useful on their own. They should always be interpreted along with the results of other tests. Calcium and phosphate levels are often measured at the same time.


  • Urine phosphorus level - 24h urine collection [ Time Frame: Phase II: termination of study (Day 70) ] [ Designated as safety issue: Yes ]

    The phosphate urine test measures the amount of phosphate in a sample of urine collected over 24 hours (24-hour urine test). Phosphate is a charged ion that contains the mineral phosphorus.

    Results of a test to measure phosphate in urine are seldom useful on their own. They should always be interpreted along with the results of other tests. Calcium and phosphate levels are often measured at the same time.



Estimated Enrollment: 20
Study Start Date: April 2013
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: amorphous calcium carbonate
50, 100 and 200 mg elemental calcium tablets, according to the doctor's decision
Dietary Supplement: amorphous calcium carbonate
Other Name: ACC
Active Comparator: crystalline calcium supplements
Tablets, according to the doctor's decision
Dietary Supplement: crystalline calcium supplements
Other Name: CCS

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Primary Hypoparathyroidism - low levels of intact PTH during hypocalcemia at diagnosis.
  • Subjects receiving calcium and vitamin D supplementation at least 1 year prior to the beginning of the study.
  • Subjects able to adhere to the visit schedule and protocol requirements and be available to complete the study.
  • Subjects who provide written informed consent to participate in the study.
  • Age: 18-80, inclusive.

Exclusion Criteria:

  • Calcium (albumin corrected) serum values below 7.0 mg/dL or above 10.0 mg/dL
  • Any known diseases affecting the absorption from the gastrointestinal tract:

    • Inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
    • Chronic diarrhea
  • Subjects with neuropsychiatric disease.
  • Subjects with impaired renal function (glomerular filtration rate, ≤40 mL/min)
  • Subjects with other severe chronic disease requiring long-term therapy.
  • Impaired liver function (Liver enzymes> x3 upper limit of normal).
  • Subjects with history or presence of kidney stones
  • Recurrent urinary tract infections
  • Subjects taking drugs which might affect calcium levels such as:

    • Fusid
    • Anticonvulsants
    • Carbonic anhydrase
    • Adrenocorticosteroids
  • Subjects who are non-cooperative or unwilling to sign consent form.
  • Pregnant or breast-feeding women.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01815021

Contacts
Contact: Michal Michal Daniely, Ph.D +972-(0)54-3001015 michald@amorphical.com

Locations
Israel
Rambam Health Care Campus Not yet recruiting
Haifa, Israel, 31096
Contact: Aliza Willaume    +97248541533    a_willaume@rambam.health.gov.il   
Contact: Marina Hefetz-Kustanovich    +97248541533    m_hefetz@rambam.health.gov.il   
Principal Investigator: Sophia Ish-Shalom, MD         
Sponsors and Collaborators
Amorphical Ltd.
Investigators
Principal Investigator: Sophia Ish-Shalom, MD
Study Director: Michal Daniely, Ph.d Amorphical Ltd.
  More Information

No publications provided

Responsible Party: Amorphical Ltd.
ClinicalTrials.gov Identifier: NCT01815021     History of Changes
Other Study ID Numbers: AMCS 009
Study First Received: March 7, 2013
Last Updated: March 19, 2013
Health Authority: Israel: Ministry of Health

Additional relevant MeSH terms:
Hypoparathyroidism
Parathyroid Diseases
Endocrine System Diseases
Calcium, Dietary
Calcium Carbonate
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antacids
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 29, 2014