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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02527668
Recruitment Status : Completed
First Posted : August 19, 2015
Last Update Posted : April 30, 2019
Sponsor:
Collaborators:
University of Zurich
Tufts University
Information provided by (Responsible Party):
DSM Nutritional Products, Inc.

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.

Condition or disease Intervention/treatment Phase
Osteopenia/Osteoporosis Dietary Supplement: Calcifediol Dietary Supplement: Vitamin D3 Other: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: To Test the Effect of Calcifediol Hy.D Supplementation on Muscle Function and Bone Quality in Younger Postmenopausal Women With Osteopenia: a Double-blind Randomized Placebo-controlled Trial
Actual Study Start Date : September 2015
Actual Primary Completion Date : September 2018
Actual Study Completion Date : December 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Calcifediol Hy.D (25-hydroxyvitamin D)
20 μg Calcifediol Hy.D (25-hydroxyvitamin D) (one capsule) per day for 6 months
Dietary Supplement: Calcifediol
One capsule orally of Calcifediol (20 µg) per day with a meal for a duration of 6 months
Other Name: 25-hydroxyvitamin D (Hy.D)

Active Comparator: Vitamin D3 (cholecalciferol)
3200 IU Vitamin D3 (cholecalciferol) (one capsule) per day for 6 months
Dietary Supplement: Vitamin D3
One capsule orally of Cholecalciferol (3200 IU) per day with a meal for a duration of 6 months
Other Name: Cholecalciferol

Placebo Comparator: Placebo
1 Placebo capsule per day for 6 months
Other: Placebo
One capsule orally of a Placebo capsule per day with a meal for a duration of 6 months




Primary Outcome Measures :
  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) [ Time Frame: Baseline, 3 months, 6 months ]
    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.


Secondary Outcome Measures :
  1. Gait speed measurement (8-meter walk) [ Time Frame: Baseline, 3 months, 6 months ]
  2. Knee flexion and extension strength test [ Time Frame: Baseline, 3 months, 6 months ]
  3. Repeated sit-to-stand test (reaction time) [ Time Frame: Baseline, 3 months, 6 months ]
  4. Systolic and diastolic blood pressure [ Time Frame: Baseline, 3 months, 6 months ]
  5. Timed up and go test (functional mobility) [ Time Frame: Baseline, 3 months, 6 months ]

Other Outcome Measures:
  1. Bone mineral density (DXA) [ Time Frame: Baseline and 6 months ]
    spine, hip (both sides at baseline, side with lowest total femur BMD only at follow-up), radius

  2. Muscle mass (DXA) [ Time Frame: Baseline and 6 months ]
    Upper and lower extremity, body composition

  3. Bone quality (Xtreme CT): [ Time Frame: Baseline and 6 months ]
    Tibia (funding is pending), radius (funding is pending)

  4. Cognition (MoCa test score) [ Time Frame: Baseline and 6 months ]
    MoCa: Montreal Cognitive Assessment

  5. Quality of life questionnaire [ Time Frame: Baseline, 3 months, 6 months ]
    EuroQol country specific TTM Index

  6. Upper extremity test (grip strength) [ Time Frame: Baseline, 3 months, 6 months ]
  7. Cardiovascular fitness (6-minute walking test) [ Time Frame: Baseline, 3 months, 6 months ]
  8. Cardio vascular risk marker (NT-BNP) [ Time Frame: Baseline, 3 months, 6 months ]
  9. Bone marker: P1NP [ Time Frame: Baseline, 3 months, 6 months ]
  10. Bone marker: Osteocalcin [ Time Frame: Baseline, 3 months, 6 months ]
  11. Bone marker: Sclerostin [ Time Frame: Baseline, 3 months, 6 months ]
  12. Muscle marker: myostatin [ Time Frame: Baseline, 3 months, 6 months ]
  13. Safety: Serum calcium adjusted for albumin [ Time Frame: Screening, 3 months, 6 months ]
  14. Safety: Serum creatinine [ Time Frame: Screening, 3 months, 6 months ]
  15. Safety: Urinary calcium/creatinine Ratio [ Time Frame: Screening, 3 months, 6 months ]
  16. Safety: Blood pressure [ Time Frame: Screening, 3 months, 6 months ]
  17. Safety: Pulse rate [ Time Frame: Screening, 3 months, 6 months ]
  18. Ancillary studies: Analysis of expression of the vitamin D receptor (VDR) in skeletal muscle [ Time Frame: Baseline, 6 months ]
    18 of 50 participants in active group I, active group II and control will be enrolled in the muscle biopsy ancillary study. The muscle biopsies (about 0.2 g) will be taken from mid-thigh at baseline and at 6 months follow-up. Biopsies will be taken at the Zurich site, frozen and send to the Tufts University Boston, USA for analysis. Analysis: Expression of the vitamin D receptor (VDR) in skeletal muscle

  19. Ancillary studies: Analysis of total cross-sectional area (CSA) of muscle fibers [ Time Frame: Baseline, 6 months ]
    18 of 50 participants in active group I, active group II and control will be enrolled in the muscle biopsy ancillary study. The muscle biopsies (about 0.2 g) will be taken from mid-thigh at baseline and at 6 months follow-up. Biopsies will be taken at the Zurich site, frozen and send to the Tufts University Boston, USA for analysis. Analysis: Total cross-sectional area (CSA) of muscle fibers

  20. Ancillary studies: Dried blood spot [ Time Frame: Baseline, 3 months ]
    Among all 150 participants, we compare 25(OH)D content in arterial finger tip blood and venous blood at baseline and at 3 months



Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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
  • 25(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

Exclusion Criteria:

  • 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.
  • Individual is unlikely to adhere to the study procedures, to keep appointments, or is planning to relocate during the study.
  • Individuals who are planning a stay in a "sunny" location (e.g. winter sun resort) for more than one month during the course of the study
  • Medication which has an effect on 25-hydroxyvitamin D level (e.g. certain anticonvulsants (e.g. Phenobarbital, Carbamazepin, Phenytoin))
  • M. Paget (Ostitis deformans)
  • Inflammatory arthritis (e.g. rheumatoid arthritis, Reiter syndrome, psoriasis arthritis)
  • Participation in a study in the last 6 months, except for studies without drug-application, or any influence of the study-medication can be excluded

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02527668


Locations
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Switzerland
Center on Aging and Mobility, Klinik für Geriatrie, UniversitätsSpital Zürich
Zurich, Switzerland, 8091
Sponsors and Collaborators
DSM Nutritional Products, Inc.
University of Zurich
Tufts University
Investigators
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Principal Investigator: Heike Bischoff-Ferrari, Prof, Dr.PH Center on Aging and Mobility, Klinik für Geriatrie, UniversitätsSpital Zürich
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Responsible Party: DSM Nutritional Products, Inc.
ClinicalTrials.gov Identifier: NCT02527668    
Other Study ID Numbers: 2013-11-25-HyD-O
000000198 ( Other Identifier: SNCTP No. )
First Posted: August 19, 2015    Key Record Dates
Last Update Posted: April 30, 2019
Last Verified: April 2019
Additional relevant MeSH terms:
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Osteoporosis
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Metabolic Diseases
Vitamin D
Cholecalciferol
Calcifediol
Hydroxycholecalciferols
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Calcium-Regulating Hormones and Agents