To Test the Effect of Calcifediol Hy.D Supplementation on Muscle Function and Bone Quality in Younger Postmenopausal Women With Osteopenia

NCT02527668 | Completed Phase 2

• 2 other identifiers: 2013-11-25-HyD-O000000198
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Young postmenopausal women with osteopenia / or women with osteoporosis and a FRAX score below pharmacologic treatment indication have limited treatment options in the prevention of osteoporosis/treatment of osteopenia. Further, there is a concern about long-term side effects of bisphosphonate treatment among young postmenopausal women, and hormone replacement therapy has been controversial. In a pilot study 20 microgram Calcifediol Hy.D improved several muscle related function in this target population within 4 months of treatment, which can help to prevent falls and associated bone fractures. Thus the main aim of this study is to test whether Calcifediol Hy.D at a daily dose of 20 μg / day improves muscle function (lower extremity test battery) compared with (1) placebo and compared with (2) 3200 Vitamin D3 IU per day, at 3 and 6 month follow-up. As a secondary and exploratory objective of this study, the investigators will compare the beforementioned doses on muscle strength and the quality of the bones, beside muscle mass, body composition and systolic and diastolic blood pressure measurements.

Conditions

Osteopenia/Osteoporosis

Outcome Measures

Primary Outcomes (1)

• Overall assessment of the "lower extremity function" test battery (difference in proportion of those who improved or maintained function compared to those who declined in function by treatment group)

  The "lower extremity function" test battery consists of: 8-meter walk test, repeated sit-to-stand test and knee flexion and extension strength test). A repeated measures analysis across all four test battery components simultaneously documenting the difference in proportion of those who improved or maintained function compared to those who declined in function by treatment group (comprised endpoint on lower extremity function) will be performed. Calcifediol Hy.D will be compared with (1) placebo and compared with (2) 3200 Vitamin D3 IU per day -for the time points baseline 3 and 6 months. Outcomes of the individual tests are subject to the secondary outcome measures.

  Baseline, 3 months, 6 months

Secondary Outcomes (5)

• Gait speed measurement (8-meter walk)

  Baseline, 3 months, 6 months

• Knee flexion and extension strength test

  Baseline, 3 months, 6 months

• Repeated sit-to-stand test (reaction time)

  Baseline, 3 months, 6 months

• Systolic and diastolic blood pressure

  Baseline, 3 months, 6 months

• Timed up and go test (functional mobility)

  Baseline, 3 months, 6 months

Other Outcomes (20)

• Bone mineral density (DXA)

  Baseline and 6 months

• Muscle mass (DXA)

  Baseline and 6 months

• Bone quality (Xtreme CT):

  Baseline and 6 months

Study Arms (3)

Calcifediol Hy.D (25-hydroxyvitamin D)

EXPERIMENTAL

20 μg Calcifediol Hy.D (25-hydroxyvitamin D) (one capsule) per day for 6 months

Dietary Supplement: Calcifediol

Vitamin D3 (cholecalciferol)

ACTIVE COMPARATOR

3200 IU Vitamin D3 (cholecalciferol) (one capsule) per day for 6 months

Dietary Supplement: Vitamin D3

Placebo

PLACEBO COMPARATOR

1 Placebo capsule per day for 6 months

Other: Placebo

Interventions

Calcifediol DIETARY_SUPPLEMENT

One capsule orally of Calcifediol (20 µg) per day with a meal for a duration of 6 months

Also known as: 25-hydroxyvitamin D (Hy.D)

Calcifediol Hy.D (25-hydroxyvitamin D)

Vitamin D3 DIETARY_SUPPLEMENT

One capsule orally of Cholecalciferol (3200 IU) per day with a meal for a duration of 6 months

Also known as: Cholecalciferol

Vitamin D3 (cholecalciferol)

Placebo OTHER

One capsule orally of a Placebo capsule per day with a meal for a duration of 6 months

Placebo

Eligibility Criteria

• Age: 50 Years - 70 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women age 50 to 70
• Post-menopausal (defined as: at least 1 year after the last menstrual period)
• community-dwelling and ambulatory without help
• with documented osteopenia (BMD by DEXA t-score: \< -1.0 and \> -2.5 at the spine or hip) in the 6 months prior to enrolment or with documented osteoporosis (BMD by DEXA t-score: ≤ -2.5 at the spine or hip) and a FRAX score (online calculation tool of absolute 10 year fracture risk) below the Swiss age-dependent indication threshold for pharmacologic treatment for the 10-year risk of major osteoporotic fractures - at the screening visit and including DEXA (in the 6 months prior to enrolment) as part of the calculation
• body mass index \> 18.5 and \< 30 kg/m2
• (OH)D level \< 24 µg/l (\< 60 nmol/l)
• understands German in reading and writing plus able to read, understand, and complete questionnaires and tests
• willingness to limit additional vitamin D3 intake to 800 IU per day
• willingness to limit calcium supplement intake to 500 mg/day
• willingness to stop active vitamin D metabolites
• participant understands the study procedures, alternative treatments available and risks involved with the study and voluntarily agrees to participate by giving a written informed consent
• participant meets the routine clinical laboratory safety screening tests performed at screening visit
• participant is able and willing to perform all study tests, attend all required office visits, and provide blood and urine samples
• participant is able to swallow the study medication

You may not qualify if:

• Consumption of more than 1'000 IU vitamin D on any day in the 4 weeks prior to enrollment.
• Elevated serum calcium \> 2.60 mmol/l adjusted for albumin if albumin ≤ 35 or ≥ 45g/l
• estimated creatinine clearance \< 30 ml/min (Cockcroft and Gault = 140 - age(yr)\*weight(kg)/ serum Cr(mmol/l))×(1.04 for women)
• severe visual or hearing impairment
• malabsorption syndrome (celiac diseases, inflammatory bowel disease).
• Pathologic fracture (excl. fractures due to osteoporosis) in the last year
• Fracture due to osteoporosis in the last 10 years
• Chemo therapy / Radiation due to cancer in the last year
• Treatment which has an effect on calcium metabolism (e.g. PTH, calcitonin, chronic cortisone intake \> 5mg/day for more than 4 weeks in the last 12 months (except for inhalation and sporadic infiltration))
• Current treatment with a bisphosphonate
• For participants of the ancillary study "Muscle Biopsy" only: Treatment which has an effect on blood coagulation (e.g. factor X inhibitor, thrombin inhibitor, NSAR, low-molecular heparin, inhibitor for platelet aggregation, vitamin K antagonist) and/or abnormal blood coagulation status .
• Unwilling or unable to take study medication
• Diseases with a risk of recurrent falling (e.g. Parkinson's disease/syndrome, Hemiplegia after stroke, symptomatic stenosis of the spinal canal, polyneuropathy, epilepsy, recurring vertigo, recurring syncope)
• History of or current diseases that may enhance serum calcium: sarcoidosis, lymphoma, primary hyperparathyroidism
• Individual that heavily consumes alcohol containing products defined as greater than (\>) 3 drinks (beer, wine, or distilled spirits) of alcoholic beverages per day.

Sponsors & Collaborators

• DSM Nutritional Products, Inc.: lead
• University of Zurich: collaborator
• Tufts University: collaborator

Study Sites (1)

Center on Aging and Mobility, Klinik für Geriatrie, UniversitätsSpital Zürich

Zurich, 8091, Switzerland

Location

Related Publications (2)

• Bischoff-Ferrari HA, Dawson-Hughes B, Orav JE, Ceglia L, Egli A, Kistler-Fischbacher M, Wieczorek M, de Godoi Rezende Costa Molino C. Effect of calcifediol and cholecalciferol on muscle function in postmenopausal women: a randomized controlled trial. Osteoporos Int. 2025 Jun;36(6):1007-1018. doi: 10.1007/s00198-025-07456-7. Epub 2025 Apr 9.

  PMID: 40205202 DERIVED

• Ceglia L, Rivas DA, Schlogl M, Fielding GB, Egli A, Bischoff-Ferrari HA, Dawson-Hughes B. Effect of vitamin D3 vs. calcifediol on VDR concentration and fiber size in skeletal muscle. J Bone Miner Metab. 2023 Jan;41(1):41-51. doi: 10.1007/s00774-022-01374-y. Epub 2022 Nov 16.

  PMID: 36385193 DERIVED

MeSH Terms

Conditions

Bone Diseases, Metabolic

Interventions

Calcifediol; 25-hydroxyvitamin D; Cholecalciferol

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Hydroxycholecalciferols; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Heike Bischoff-Ferrari, Prof, Dr.PH

  Center on Aging and Mobility, Klinik für Geriatrie, UniversitätsSpital Zürich

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2015
• First Posted: August 19, 2015
• Study Start: September 1, 2015
• Primary Completion: September 1, 2018
• Study Completion: December 1, 2018
• Last Updated: April 30, 2019

Record last verified: 2019-04

Locations

CH (1)