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The Effect of Chymosin on the Intestinal Absorption of Calcium

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Aarhus
ClinicalTrials.gov Identifier:
NCT01370941
First received: April 27, 2011
Last updated: March 20, 2012
Last verified: March 2012
History of Changes
  Purpose

An adequate calcium intake is important for bone turnover and the risk of developing osteoporosis. Yet many studies have documented that supplementation with calcium tablets are often associated with a poor compliance, therefore it is important to explore ways to better calcium influx.

Calcium consumed through dairy products must first be cleaved from the molecules which it is bound to before it can be absorbed. Chymosin is an enzyme which cleaves the protein binding between some amino acids in κ-casein. The reaction occurs after ingestion of milk and causes a process whereby the time the milk is staying gastrointestinal tract is extended, this can lead to enhanced uptake of calcium.

When the body's calcium balance is in equilibrium excretion in urine (24 h) in roughly the size of the intake, whereby a measurement of circadian urine excretion of calcium can determine the amount of calcium absorbed from the intestine.

The investigators want to clarify whether the addition of chymosin to milk increases calcium absorption. Secondary to explore issues of significance for this effect, including vitamin D status and amount of daily calcium intake and whether a change in calcium absorption has immediate effects on bone turnover (measured as plasma osteocalcin, bone specific alkaline phosphatase (BSAP), and the renal excretion of cross-linked N-terminal telopeptide of type 1 collagen (NTx/Cr) ratio) and on the parathyroid function (measured as PTH). Finally we will explore relations between bone mineral density (BMD) and the measured parameters (in terms of P-PTH, P-25OHD, P-1,25(OH)2D, P-osteocalcin, P-BSAP, and U-NTx/Cr).


Condition Intervention Phase
Osteoporosis
Osteopenia
 Dietary Supplement: Drug A Chymosin
Dietary Supplement: Drug B: Placebo
 Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: The Effect of Chymosin on the Intestinal Absorption of Calcium: A Randomized Controlled Cross-over Trial

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Aarhus:

Primary Outcome Measures:
  • The effect of the intervention on the 24 hours urine excretion of calcium corrected for creatinine [ Time Frame: Two time two days over an eighteen days period ] [ Designated as safety issue: No ]
    The effect of the intervention on the 24 hours urine excretion of calcium corrected for creatinine


Secondary Outcome Measures:
  • The effect of plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels on the amount of calcium absorbed and the potential impact of chymosin [ Time Frame: Two time two days over an eighteen days period ] [ Designated as safety issue: No ]
    Vitamin D: The importance of plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D on the amount of calcium absorbed and the potential impact of chymosin.

  • The immediate biological effects of the intervention on P-PTH, and bone turnover (P-osteocalcin, P-BSAP, U-NTX) [ Time Frame: Two time two days over an eighteen days period ] [ Designated as safety issue: No ]
    The immediate biological effects of the intervention on parathyroid function (PTH) and bone turnover (P-osteocalcin, plasma bone specific alkaline phosphatase, and the renal excretion of cross-linked N-terminal telopeptide of type 1 collagen (NTx/Cr) ratio).

  • Relations between bone mineral density (BMD) and the measured parameters (P-25OHD, P-1,25(OH)2D), P-PTH, P-osteocalcin, P-BSAP, U-NTx/Cr) [ Time Frame: Will be measured one time at one of the two time two days over an eighteen days period ] [ Designated as safety issue: No ]
    To explore relations between bone mineral density (BMD) and the measured parameters (P-25OHD, P-1,25(OH)2D), P-PTH, P-osteocalcin, P-BSAP, U-NTx/Cr).


Enrollment: 125
Study Start Date: April 2011
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Drug A: Chymosin
A: 5 drops of Chymosin is added to ½ a liter of milk. This is to be consumed during breakfast.
 Dietary Supplement: Drug A Chymosin
Five drops of chymosin is added to ½ a liter of milk. This is to be consumed during breakfast.
Other Name: Chy-max plus IMCU200
Placebo Comparator: Drug B: Placebo
B: 5 drops of placebo (water) is added to ½ a liter of milk. This is to be consumed during breakfast.
 Dietary Supplement: Drug B: Placebo
B: Five drops of placebo (water) is added to ½ a liter of milk. This is to be consumed during breakfast.
Other Name: Water

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   25 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • A stable daily intake of calcium on estimated 500-1200 mg, of which dairy products are minimum 500 mg
  • Speak and read Danish.
  • Written consent after verbal and written information

Exclusion Criteria:

  • Known lactose intolerance / milk allergy
  • Use of calcium supplements in tablet or powder
  • Intake of vitamin D supplements exceeding 10 micro grams/day
  • A habitual dietary calcium intake exceeding 1200 mg/day
  • Impaired renal function (plasma creatinine >150 micro mol/L)
  • Impaired liver function (plasma ALT >200 U/L, alkaline phosphatase >400 U/L).
  • Previous or present malignancies(including metastases).
  • sarcoidosis or second granulomatous disease which has caused hypercalcaemia
  • Pregnancy, breastfeeding
  • Postmenopausal women
  • Disease or treatment with drugs known to affect calcium homeostasis, including diuretics, osteoporosis agents, lithium, steroids, etc..
  • Pledged due to chronic alcoholism.
  • Severe medical or social problems which makes it unlikely that the participant can complete the survey
  • Lack of willingness / desire to participate
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01370941

Locations
Denmark
Ward 900, Osteporosis clinic, Aarhus University Hospital, THG
Aarhus, Jutland, Denmark, 8000
Sponsors and Collaborators
University of Aarhus
Investigators
Principal Investigator: Leif Mosekilde, Professor Aarhus University Hospital, THG
  More Information

No publications provided

Responsible Party: University of Aarhus
ClinicalTrials.gov Identifier: NCT01370941     History of Changes
Other Study ID Numbers: Chymo-01, 20110007
Study First Received: April 27, 2011
Last Updated: March 20, 2012
Health Authority: Denmark: Ethics Committee

Keywords provided by University of Aarhus:
Chymosin
24H urine calcium excretion
Calcium absorption
Intestinal Absorption of Calcium

Additional relevant MeSH terms:
Bone Diseases, Metabolic
Osteoporosis
Bone Diseases
Musculoskeletal Diseases

ClinicalTrials.gov processed this record on June 13, 2013