Dose-dependent Effects of Vitamin D on Bone Health

NCT01900860 | Completed DMC

• 1 other identifier: 20130101
• Study Type: interventional
• Target: 311
• Locations: 1 country
• Sites: 1

Brief Summary

We propose to conduct a randomized double blind trial of three doses of vitamin D, 400, 4000, and 10,000 International Units (IU) per day, to assess the effect on bone density and architecture as assessed by high resolution peripheral quantitative tomography (HR-pQCT) measurements at the radius and distal tibia, and standard Dual X-ray absorptiometry (DXA). Other measures of bone and calcium metabolism will be assessed. The trial will last as long as three years. Approximately 300 healthy men and women, aged 50-70 years of age, will be recruited, and randomly assigned to one of the three doses of vitamin D. Other outcome variables assessed include quality of life, depression, muscle strength and balance.

Conditions

Age-Related Osteoporosis

Keywords

Vitamin D; Bone quality; Bone density; calcium metabolism; High resolution peripheral quantitative computed tomography; Dual X-ray absorptiometry; Quality of life

Outcome Measures

Primary Outcomes (2)

• Total Bone Mineral Density (Tt.BMD) at the distal radius and tibia, as measured by High Resolution peripheral Quantitative Tomography (HR-pQCT)

  Unlike the measurement of bone density by DXA (a secondary outcome, see below), which estimates bone density based on assumptions of the depth of a 2-dimensional image of bone, HR-pQCT measurement of Tt.BMD provides a true volume based density measurement. HR-pQCT also provides a much higher resolution image of the region of interest than the image derived from a DXA measurement. Units of this measurement are milligrams hydroxyapatite per cubic centimetre (mg HA/cm3). The analysis will examine change in Tt.BMD at distal radius and tibia from baseline to measurements at 6, 12, 24, and 36 months.

  Participants will be followed from baseline up to 36 months

• Bone strength, as estimated by Finite Element Analysis of High Resolution peripheral Quantitative Computed Tomography (HR-pQCT) measurements at the distal radius and tibia

  HR-pQCT scans provide the ability to measure a true volumetric density of the bone region of interest and to study microarchitecture of both trabecular and cortical bone, from which an assessment of strength by Finite Element Analysis (FEA) can be determined: briefly, a 3-dimensional computer model of bone can be constructed from the HR-pQCT data, and subjected to strength testing. FEA software (FAIM, version 6.0, Numerics88 Solutions, Calgary, Canada) is used to estimate failure load (N) based on 2 % of the elements exceeding 7,000 μstrain. The analysis examines change from baseline measured at 6, 12, 24, and 36 months.

  Participants will be followed from baseline up to 36 months

Secondary Outcomes (9)

• Cortical bone density (Ct.BMD) of bone as measured by HR-pQCT

  From baseline to 36 months - measured at 0, 6, 12, 24, and 36 months.

• Cortical Porosity (Ct.Po) of bone as measured by HR-pQCT

  From baseline to 36 months - measured at 0, 6, 12, 24, and 36 months.

• Trabecular bone density (Tb.BMD) of bone as measured by HR-pQCT

  From baseline to 36 months - measured at 0, 6, 12, 24, and 36 months.

• Trabecular number (Tb.N) as measured by HR-pQCT

  From baseline to 36 months - measured at 0, 6, 12, 24, and 36 months.

• Bone Mineral Density as measured by Dual X-ray Absorptiometry

  Participants will be followed from baseline up to 36 months

Other Outcomes (3)

• Safety: changes in parameters of calcium metabolism

  Participants will be followed from baseline up to 36 months

• Safety: Parameters of glucose metabolism

  Participants will be followed from baseline up to 36 months

• Safety: Peripheral Vascular Calcification, as assessed by HR-pQCT at the distal radius and tibia

  Participants imaging studies will be followed from baseline up to 36 months

Study Arms (3)

vitamin D 10,000 IU

ACTIVE COMPARATOR

Subjects in this arm receive 10,000 IU Vitamin D p.o. (as 5 drops of a blinded vitamin D solution) per day. Duration: 3 years

Dietary Supplement: Vitamin D

Vitamin D 4000 IU

ACTIVE COMPARATOR

Subjects in this arm receive 4,000 IU Vitamin D p.o. (as 5 drops of a blinded vitamin D solution) per day. Duration: 3 years

Dietary Supplement: Vitamin D

Vitamin D 400 IU

ACTIVE COMPARATOR

Subjects in this arm receive 400 IU Vitamin D p.o. (as 5 drops of a blinded vitamin D solution) per day. Duration: 3 years

Dietary Supplement: Vitamin D

Interventions

Vitamin D DIETARY_SUPPLEMENT

Three different doses of vitamin D will be administered in a double-blinded fashion. The three doses are 400, 4000, or 10,000 IU/day

Also known as: Vitamin D3, Cholecalciferol

Vitamin D 400 IU; Vitamin D 4000 IU; vitamin D 10,000 IU

Eligibility Criteria

• Age: 55 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy women and men between 55 and 70 years of age; women will be at least 5 years post-menopause. Presence of a chronic illness does not exclude participation if the condition is stable and managed by a physician.
• Baseline lumbar spine and total hip bone mineral density (BMD) T-score above 2.5 as assessed using dual x-ray absorptiometry (DXA).

You may not qualify if:

• A serum 25-\[OH\] vitamin D (25OHD) of \<30 nmol/L (\<12 ng/mL) or \>125 nmol/L (50 ng/mL).
• Hypercalcemia (serum calcium \>2.55 mmol/L), hypocalcemia (serum calcium \<2.10 mmol/L) or eGFR \<30 mL/min.
• Surgical cure of Primary Hyperparathyroidism within the last year.
• Active kidney stone disease (recurrent stones, recent kidney stone \[within last 2 years\])
• Known hypersensitivity or allergy to Vitamin D
• Serum creatinine, AST, ALT, PTH, calcium, or alkaline phosphatase greater than 1.5 times the upper limit of normal at the screening visit
• High 10-year risk for osteoporotic fracture, as defined by the Canadian Association of Radiologists/Osteoporosis Canada calculator, or the World Health Organization's FRAX calculator.
• DXA T-score below or equal to -2.5 SD.
• Have taken bone active osteoporosis prescription drugs in the past 2 years (bisphosphonates) or 1 year (other osteoporosis prescription therapies).
• Any medical condition that would prevent participation in a clinical trial for a full three years.
• Medications such as prednisone \>2.5 mg daily (or equivalent); other bone active medications such as tamoxifen or aromatase inhibitors for breast cancer, or androgen deprivation therapy of prostate cancer.
• Disorders known to affect vitamin D metabolism such as sarcoidosis or renal failure or malabsorption disorders (e.g. pancreatic insufficiency or celiac disease).
• Regular (monthly or more frequent) use of tanning salons.

Sponsors & Collaborators

• University of Calgary: lead
• Pure North S'Energy Foundation: collaborator

Study Sites (1)

The University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

Related Publications (5)

• Burt LA, Gaudet S, Kan M, Rose MS, Billington EO, Boyd SK, Hanley DA. Methods and procedures for: A randomized double-blind study investigating dose-dependent longitudinal effects of vitamin D supplementation on bone health. Contemp Clin Trials. 2018 Apr;67:68-73. doi: 10.1016/j.cct.2018.02.009. Epub 2018 Feb 20.

  PMID: 29471124 BACKGROUND

• Burt LA, Billington EO, Rose MS, Kremer R, Hanley DA, Boyd SK. Adverse Effects of High-Dose Vitamin D Supplementation on Volumetric Bone Density Are Greater in Females than Males. J Bone Miner Res. 2020 Dec;35(12):2404-2414. doi: 10.1002/jbmr.4152. Epub 2020 Sep 16.

  PMID: 32777104 DERIVED

• Billington EO, Burt LA, Plett R, Rose MS, Boyd SK, Hanley DA. Effect of high-dose vitamin D supplementation on peripheral arterial calcification: secondary analysis of a randomized controlled trial. Osteoporos Int. 2020 Nov;31(11):2141-2150. doi: 10.1007/s00198-020-05500-2. Epub 2020 Jun 15.

  PMID: 32556518 DERIVED

• Billington EO, Burt LA, Rose MS, Davison EM, Gaudet S, Kan M, Boyd SK, Hanley DA. Safety of High-Dose Vitamin D Supplementation: Secondary Analysis of a Randomized Controlled Trial. J Clin Endocrinol Metab. 2020 Apr 1;105(4):dgz212. doi: 10.1210/clinem/dgz212.

  PMID: 31746327 DERIVED

• Burt LA, Billington EO, Rose MS, Raymond DA, Hanley DA, Boyd SK. Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength: A Randomized Clinical Trial. JAMA. 2019 Aug 27;322(8):736-745. doi: 10.1001/jama.2019.11889.

  PMID: 31454046 DERIVED

MeSH Terms

Conditions

Osteoporosis

Interventions

Vitamin D; Cholecalciferol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• David A Hanley, MD, FRCPC

  The University of Calgary

  PRINCIPAL INVESTIGATOR

• Steven K Boyd, PhD

  The University of Calgary

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Emeritus, Department of Medicine

Study Record Dates

• First Submitted: July 2, 2013
• First Posted: July 17, 2013
• Study Start: August 1, 2013
• Primary Completion: December 7, 2017
• Study Completion: December 31, 2017
• Last Updated: April 17, 2019

Record last verified: 2019-04

Locations

CA (1)