ValoRization of Dairy Sidestreams to Fight Calcium dEficits iN Postmenopausal Women (RENEW)

ValoRization of Dairy Sidestreams to Fight Calcium dEficits iN Postmenopausal Women - A Randomized Controlled Double-blinded Intervention Trial

The primary objective of this study is to investigate the effects of 12-months supplementation with calcium-enriched permeate, taken alone or in conjunction with inulin, on changes in markers of bone formation and resorption and in bone mass density (BMD) in apparently healthy postmenopausal women compared with calcium-carbonate or maltodextrin supplementation.

Study Overview

• Status: Completed
• Conditions: Osteoporosis, Postmenopausal
• Intervention / Treatment: Dietary supplement: Maltodextrin; Dietary supplement: Calcium-carbonate; Dietary supplement: Calcium-enriched permeate; Dietary supplement: Calcium-enriched permeate with Inulin

Detailed Description

The study will include an information visit, a randomization visit, a month 3 visit and a final visit at month 12. Besides, two visits at month 6 and 9 for dispensing of trial products. Outcome parameters will be measured using blood samples obtained at the randomization visit, the month 3 visit and at the final visit at month 12. Outcome parameters will moreover be analyzed based on DXA scan obtained at the randomization visit and at the final visit at 12 months.

• Study Type: Interventional
• Enrollment (Actual): 420
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Køge, Denmark, 4600
    • Zealand University Hospital
  • Frederiksberg
    • Copenhagen, Frederiksberg, Denmark
      • Copenhagen University, Department of Nutrition, Exercise and Sports, Section for Clinical and Preventive Nutrition

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Subject is between 45 years and 65 years of age by the time of inclusion.
• Subject has been menopausal for at least 1 year, defined as 12 months after last bleeding and up to 10 years.
• Subject is Caucasian.
• Has a BMI below 35.0.
• Holder of a computer.
• Has a sufficient vitamin D status (plasma 25OHD concentration > 50 nmol/L).
• Subject is willing and able to provide written informed consent prior to participation.

Exclusion Criteria:

• Subject taking supplements or medicine that affects calcium and bone metabolism e.g. diuretics or hormone replacement therapy evaluated by the investigator.
• Intake of antibiotics in the last 3 months before enrollment.
• Subject with an osteoporosis diagnosis or history of osteoporotic fractures.
• Presence of renal, gastrointestinal, hepatic or endocrinological diseases.
• Subject with any serious illness or history of cancer within the past 5 years (except adequately-treated localized basal cell skin cancer or in situ uterine cervical cancer).
• Known or suspected abuse of alcohol or recreational drugs.
• Known milk allergy.
• Known or suspected hypersensitivity to trial products or related products.
• Blood donation except from the donation in this study.
• Subject where it is not possible to obtain sufficient data.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Product with placebo (no calcium supplementation).; Maltodextrin with 0 mg calcium in capsules and sachets consumed orally daily for one year.	Dietary supplement: Maltodextrin; Three capsules are to be consumed with one sachet dissolved in 200 ml. of water for breakfast and later for dinner resulting in a total of six capsules and two sachets via oral consumption daily.
Active Comparator: Product with calcium-carbonate; 800 mg calcium as calcium-carbonate in capsules and sachets consumed orally daily for one year.	Dietary supplement: Calcium-carbonate; Three capsules are to be consumed with one sachet dissolved in 200 ml. of water for breakfast and later for dinner resulting in a total of six capsules and two sachets via oral consumption daily.
Experimental: Product with calcium-enriched permeate "Capolac"; 800 mg of calcium from calcium-enriched permeate in capsules and sachets consumed orally daily for one year.	Dietary supplement: Calcium-enriched permeate; Three capsules are to be consumed with one sachet dissolved in 200 ml. of water for breakfast and later for dinner resulting in a total of six capsules and two sachets via oral consumption daily.; Other Names: Capolac
Experimental: Product with calcium-enriched permeate "Capolac" and Inulin; 800 mg of calcium from calcium-enriched permeate and 12 g inulin in capsules and sachets consumed orally daily for one year.	Dietary supplement: Calcium-enriched permeate with Inulin; Three capsules are to be consumed with one sachet dissolved in 200 ml. of water for breakfast and later for dinner resulting in a total of six capsules and two sachets via oral consumption daily.; Other Names: Capolac Inulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in bone turnover marker CTX.	Changes in fasting blood samples of bone turnover marker CTX attained at randomization, 3 months visit and 12 months visit (final visit)	1 year
The change in bone turnover marker P1NP.	Changes in fasting blood samples of bone turnover marker (P1NP) attained at randomization, 3 months visit and 12 months visit (final visit)	1 year
The change in loss of bone mineral density.	Changes in DXA scan results of BMD (femur) and BMD (lumbar spine) attained at randomization and 12 months visit (final visit)	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in blood parameters of iPTH	Changes in fasting blood samples of iPTH attained at randomization and 12 months visit (final visit)	1 year
Changes in blood parameters of Vitamin D	Changes in fasting blood samples of vitamin D attained at randomization and 12 months visit (final visit)	1 year
Changes in blood parameters of total calcium	Changes in fasting blood samples of total calcium attained at randomization and 12 months visit (final visit)	1 year
Changes in blood parameters of phosphate	Changes in fasting blood samples of phosphate attained at randomization and 12 months visit (final visit)	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in BMI	Changes in BMI from randomization to 12 months visit (final visit)	1 year
Changes in physical activity	Changes in physical activity level attained by IPAQ from randomization to 12 months visit (final visit)	1 year
Changes in habitual dietary intake	Changes in habitual dietary intake attained by Myfood24 7-day recording from randomization to 12 months visit (final visit)	1 year
Changes in fecal pH	Changes in fecal pH from randomization to 12 months visit (final visit)	1 year
Changes in gut microbiome	Changes in microbial taxonomy and microbial gene content measured via sequencing of DNA extracted from fecal samples from randomization to 12 months visit (final visit)	1 year
Changes in urinary metabolites	Changes in urine metabolites from randomization to 12 months visit (final visit) by NMR spectroscopy to detect and quantify about 50 metabolites including creatinine, amines, amino acids, alcohols, carboxylic acids including short-chain fatty acids, keto acids, purine, pyridine and pyrimidine derivatives, sugars and derivatives.	1 year
Changes in fecal metabolites	Changes in fecal metabolites from randomization to 12 months visit (final visit) by NMR spectroscopy to detect and quantify about 50 metabolites including creatine, creatinine, amines, amino acids, carboxylic acids including short-chain fatty acids, keto acids, nucleotides and derivatives.	1 year

Collaborators and Investigators

• Sponsor: University of Copenhagen
• Collaborators: Zealand University Hospital
• Investigators: Principal Investigator: Mette F Hitz, Doctor, Zealand University Hospital, Køge

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2021
• Primary Completion (Actual): July 4, 2023
• Study Completion (Actual): July 4, 2023

Study Registration Dates

• First Submitted: March 30, 2021
• First Submitted That Met QC Criteria: April 7, 2021
• First Posted (Actual): April 8, 2021

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: October 5, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis; Osteoporosis, Postmenopausal; 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: M236

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The results will be analyzed and attempted published in international journals regardsless of whether the study leads to positive, negative or inconclusive results. The study protocol will be registered and made publicly avalailable at www.clinicaltrials.gov.

Drug and device information, study documents

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