NCT01370941

Brief Summary

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
125

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Apr 2011

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2011

Completed
26 days until next milestone

First Submitted

Initial submission to the registry

April 27, 2011

Completed
1 month until next milestone

First Posted

Study publicly available on registry

June 10, 2011

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2012

Completed
Last Updated

March 21, 2012

Status Verified

March 1, 2012

Enrollment Period

11 months

First QC Date

April 27, 2011

Last Update Submit

March 20, 2012

Conditions

OsteoporosisOsteopenia

Keywords

Chymosin24H urine calcium excretionCalcium absorptionIntestinal Absorption of Calcium

Outcome Measures

Primary Outcomes (1)

  • The effect of the intervention on the 24 hours urine excretion of calcium corrected for creatinine

    The effect of the intervention on the 24 hours urine excretion of calcium corrected for creatinine

    Two time two days over an eighteen days period

Secondary Outcomes (3)

  • 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

    Two time two days over an eighteen days period

  • The immediate biological effects of the intervention on P-PTH, and bone turnover (P-osteocalcin, P-BSAP, U-NTX)

    Two time two days over an eighteen days period

  • 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)

    Will be measured one time at one of the two time two days over an eighteen days period

Study Arms (2)

Drug A: Chymosin

ACTIVE COMPARATOR

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

Drug B: Placebo

PLACEBO COMPARATOR

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

Interventions

Drug A ChymosinDIETARY_SUPPLEMENT

Five drops of chymosin is added to ½ a liter of milk. This is to be consumed during breakfast.

Also known as: Chy-max plus IMCU200
Drug A: Chymosin
Drug B: PlaceboDIETARY_SUPPLEMENT

B: Five drops of placebo (water) is added to ½ a liter of milk. This is to be consumed during breakfast.

Also known as: Water
Drug B: Placebo

Eligibility Criteria

Age25 Years - 40 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Ward 900, Osteporosis clinic, Aarhus University Hospital, THG

Aarhus, Jutland, 8000, Denmark

Location

Related Publications (1)

  • Moller UK, Jensen LT, Mosekilde L, Rejnmark L. Effects of adding chymosin to milk on calcium homeostasis: a randomized, double-blind, cross-over study. Calcif Tissue Int. 2015 Feb;96(2):105-12. doi: 10.1007/s00223-014-9942-8. Epub 2014 Dec 18.

    PMID: 25515208DERIVED

MeSH Terms

Conditions

OsteoporosisBone Diseases, Metabolic

Interventions

Water

Condition Hierarchy (Ancestors)

Bone DiseasesMusculoskeletal DiseasesMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

HydroxidesAlkaliesInorganic ChemicalsAnionsIonsElectrolytesOxidesOxygen Compounds

Study Officials

  • Leif Mosekilde, Professor

    Aarhus University Hospital, THG

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 27, 2011

First Posted

June 10, 2011

Study Start

April 1, 2011

Primary Completion

March 1, 2012

Study Completion

March 1, 2012

Last Updated

March 21, 2012

Record last verified: 2012-03

Locations

DK(1)