Vitamin D Repletion in Primary Hyperparathyroidism

• Sponsor: Columbia University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01306656
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 9
• Location: 1
• Arms: 2
• Actual Duration (Months): 64.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study will look at the effect of 2 treatment regimens that contain vitamin D in a six-month treatment trial of patients with PHPT who are vitamin D deficient. Patients will be assigned randomly to one of 2 regimens, and will be followed with tests of their blood, urine and bones. This study should provide important information on the effect of vitamin D therapy in patients with PHPT. In addition, data from this study will guide physicians as to how best to treat their patients who have PHPT and vitamin D deficiency.

Condition or Disease	Intervention/Treatment	Phase
Primary Hyperparathyroidism; Vitamin D Deficiency	Drug: 10,000 IU Vitamin D3; Other: Placebo; Dietary Supplement: Vitamin D	Phase 4

Detailed Description

Primary hyperparathyroidism (PHPT) is a common disease in which the parathyroid glands produce excessive amounts of parathyroid hormone (PTH), which regulates calcium levels. In primary hyperparathyroidism, high levels of PTH remove too much calcium from bones and deposit the excess calcium in the blood, which is then filtered into the urine by the kidneys. Bone health is threatened by the excess calcium loss which weakens the structure of the bones.

Many patients with primary hyperparathyroidism also have low vitamin D (25OHD) levels which is thought to further impair bone health. Recent medical guidelines recommend treating patients with primary hyperparathyroidism who have low vitamin D levels with oral vitamin D but the optimal vitamin D dose and rate of repletion is unclear. It is, therefore, important to determine if replenishing Vitamin D will improve bone health in primary hyperparathyroidism, and if so, to assess the impact of the rate of vitamin D repletion.

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Active arm: Month 1: 20,000 IU vitamin D3 once a week, plus daily multivitamin with 400 IU vitamin D. Months 2-6: 10,000 IU vitamin D3 once a week, plus daily multivitamin with 400 IU vitamin D. Placebo arm: Month 1: Placebo once a week plus daily multivitamin with 400 IU vitamin D. Months 2-6: Placebo every week plus daily multivitamin with 400 IU vitamin D.Active arm:Month 1: 20,000 IU vitamin D3 once a week, plus daily multivitamin with 400 IU vitamin D. Months 2-6: 10,000 IU vitamin D3 once a week, plus daily multivitamin with 400 IU vitamin D.Placebo arm:Month 1: Placebo once a week plus daily multivitamin with 400 IU vitamin D. Months 2-6: Placebo every week plus daily multivitamin with 400 IU vitamin D.
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: Patient, investigator and study team will be blinded to study arm ramdomization.
• Primary Purpose: Treatment
• Official Title: Randomized Controlled Trial of Vitamin D Repletion Regimens in Primary Hyperparathyroidism
• Actual Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Feb 1, 2017
• Actual Study Completion Date: Feb 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 10,000 IU Vitamin D3 plus a multivitamin with 400 IU vitamin D	Drug: 10,000 IU Vitamin D3; Month 1: 20,000 IU vitamin D3 once a week Months 2-6: 10,000 IU vitamin D3 once a week; Other Names: Cholecalciferol-D3 ; Dietary Supplement: Vitamin D; Daily multivitamin with 400 IU vitamin D.; Other Names: cholecalciferol
Placebo Comparator: Group 2 Placebo plus a multivitamin with 400 IU vitamin D	Other: Placebo; Month 1: Placebo once a week Months 2-6: Placebo once a week; Other Names: Placebo pill ; Dietary Supplement: Vitamin D; Daily multivitamin with 400 IU vitamin D.; Other Names: cholecalciferol

Outcome Measures

Primary Outcome Measures

1. Serum Parathyroid Hormone (PTH) Level [6 months]

   This is designed to measure how many participants will achieve PTH > 65 pg/mL.

Secondary Outcome Measures

1. Areal Bone Mineral Density of the Lumbar Spine [6 months]

   Measured by dual-energy x-ray absorptiometry (DEXA) scan

2. Trabecular Bone Density at the Forearm [6 months]

   Measured by high resolution peripheral quantitative computed tomography

3. Change in Urinary Calcium Level [1 month, 3 months, 6 months]

   This is designed to measure how the study treatment will affect urinary calcium level over time.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosed PHPT, defined by an elevated serum calcium level (we will not study normocalcemic PHPT) with elevated or inappropriately normal PTH levels.

• Vitamin D3 less than 30 ng/ml

Exclusion Criteria:

• Patients with familial hyperparathyroid syndromes

• Current or past use of the following medications: bisphosphonate within past 2 years, use of lithium or thiazide diuretics, current use of cinacalcet, use of aluminum containing medications, cimetidine, colestipol, or orlistat

• Malignancy, except cured basal or squamous cell skin carcinoma or other cured cancers that are at least five years free from recurrence

• History or current diagnosis of certain medical diseases (including sarcoidosis, active infectious granulomatous disease, HIV/AIDS, chronic kidney disease (serum creatinine > 1.5 mg/dL), liver disease; GI diseases known to affect calcium metabolism; secondary hyperparathyroidism);

• We will also exclude patients with calcium above 11.5 mg/dL, urine calcium above 350 mg/day, and active nephrolithiasis because vitamin D repletion could potentially exacerbate hypercalcemia or hypercalciuria

• Other exclusions include protected individuals (institutionalized), prisoners, and any other prospective participant who might not be able to give voluntary informed consent.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Columbia University Medical Center	New York	New York	United States	10032

Sponsors and Collaborators

• Columbia University
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Shonni J Silverberg, MD, Columbia University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 2, 2015

More Information

Publications

None provided.

• Responsible Party: Shonni J. Silverberg, Professor of Medicine, Columbia University
• ClinicalTrials.gov Identifier: NCT01306656
• Other Study ID Numbers: AAAF1797; R01DK084986-05
• First Posted: Mar 2, 2011
• Last Update Posted: Apr 16, 2019
• Last Verified: Mar 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Shonni J. Silverberg, Professor of Medicine, Columbia University: Endocrinology; Metabolic Bone Disease; Primary Hyperparathyroidism; PHPT; Vitamin D Deficiency; Bone Mineral Density; Hyper-calcemia
• Additional relevant MeSH terms: Vitamin D Deficiency; Hyperparathyroidism; Hyperparathyroidism, Primary; Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins

Study Results

Participant Flow

Arm/Group Title	10,000 IU Vitamin D3 + Multivitamin	Placebo + Multivitamin
Arm/Group Description	10,000 IU Vitamin D3 plus a multivitamin with 400 IU vitamin D 10,000 IU Vitamin D3: Month 1: 20,000 IU vitamin D3 once a week Months 2-6: 10,000 IU vitamin D3 once a week Vitamin D: Daily multivitamin with 400 IU vitamin D.	Placebo plus a multivitamin with 400 IU vitamin D Placebo: Month 1: Placebo once a week Months 2-6: Placebo once a week Vitamin D: Daily multivitamin with 400 IU vitamin D.
Period Title: Overall Study
STARTED	7	2
COMPLETED	6	2
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	10,000 IU Vitamin D3 + Multivitamin	Placebo + Multivitamin	Total
Arm/Group Description	10,000 IU Vitamin D3 plus a multivitamin with 400 IU vitamin D 10,000 IU Vitamin D3: Month 1: 20,000 IU vitamin D3 once a week Months 2-6: 10,000 IU vitamin D3 once a week Vitamin D: Daily multivitamin with 400 IU vitamin D.	Placebo plus a multivitamin with 400 IU vitamin D Placebo: Month 1: Placebo once a week Months 2-6: Placebo once a week Vitamin D: Daily multivitamin with 400 IU vitamin D.	Total of all reporting groups
Overall Participants	7	2	9
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	3 42.9%	1 50%	4 44.4%
>=65 years	4 57.1%	1 50%	5 55.6%
Sex: Female, Male (Count of Participants)
Female	6 85.7%	2 100%	8 88.9%
Male	1 14.3%	0 0%	1 11.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 100%	2 100%	9 100%
Not Hispanic or Latino	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	7 100%	2 100%	9 100%

Outcome Measures

1. Primary Outcome

Title	Serum Parathyroid Hormone (PTH) Level
Description	This is designed to measure how many participants will achieve PTH > 65 pg/mL.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Study enrollment did not reach the required number of subjects; the analysis results would not have been reliable or have enough statistical power. Therefore, samples were not processed and data was not available for analysis.

Arm/Group Title	10,000 IU Vitamin D3 + Multivitamin	Placebo + Multivitamin
Arm/Group Description	10,000 IU Vitamin D3 plus a multivitamin with 400 IU vitamin D 10,000 IU Vitamin D3: Month 1: 20,000 IU vitamin D3 once a week Months 2-6: 10,000 IU vitamin D3 once a week Vitamin D: Daily multivitamin with 400 IU vitamin D.	Placebo plus a multivitamin with 400 IU vitamin D Placebo: Month 1: Placebo once a week Months 2-6: Placebo once a week Vitamin D: Daily multivitamin with 400 IU vitamin D.
Measure Participants	0	0

2. Secondary Outcome

Title	Areal Bone Mineral Density of the Lumbar Spine
Description	Measured by dual-energy x-ray absorptiometry (DEXA) scan
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Study enrollment did not reach the required number of subjects; the analysis results are not reliable or have enough statistical power.

Arm/Group Title	10,000 IU Vitamin D3 + Multivitamin	Placebo + Multivitamin
Arm/Group Description	10,000 IU Vitamin D3 plus a multivitamin with 400 IU vitamin D 10,000 IU Vitamin D3: Month 1: 20,000 IU vitamin D3 once a week Months 2-6: 10,000 IU vitamin D3 once a week Vitamin D: Daily multivitamin with 400 IU vitamin D.	Placebo plus a multivitamin with 400 IU vitamin D Placebo: Month 1: Placebo once a week Months 2-6: Placebo once a week Vitamin D: Daily multivitamin with 400 IU vitamin D.
Measure Participants	6	2
Mean (Standard Deviation) [percentage of change]	-.98777 (1.662643)	1.442861 (4.376592)

3. Secondary Outcome

Title	Trabecular Bone Density at the Forearm
Description	Measured by high resolution peripheral quantitative computed tomography
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Study enrollment did not reach the required number of subjects; the analysis results are not reliable nor have enough statistical power.

Arm/Group Title	Group 1	Group 2
Arm/Group Description	10,000 IU Vitamin D3 plus a multivitamin with 400 IU vitamin D 10,000 IU Vitamin D3: Month 1: 20,000 IU vitamin D3 once a week Months 2-6: 10,000 IU vitamin D3 once a week Vitamin D: Daily multivitamin with 400 IU vitamin D.	Placebo plus a multivitamin with 400 IU vitamin D Placebo: Month 1: Placebo once a week Months 2-6: Placebo once a week Vitamin D: Daily multivitamin with 400 IU vitamin D.
Measure Participants	5	2
Mean (Standard Deviation) [percentage of change]	-1.00345 (3.912386)	-2.59816 (0.583978)

4. Secondary Outcome

Title	Change in Urinary Calcium Level
Description	This is designed to measure how the study treatment will affect urinary calcium level over time.
Time Frame	1 month, 3 months, 6 months

Outcome Measure Data

Analysis Population Description

Data is provided for 6 out of the 7 participants in Group 1 due to that 1 participant became lost to follow-up and did not complete lab testing at Month 3 and 6.

Arm/Group Title	10,000 IU Vitamin D3 + Multivitamin	Placebo + Multivitamin
Arm/Group Description	10,000 IU Vitamin D3 plus a multivitamin with 400 IU vitamin D 10,000 IU Vitamin D3: Month 1: 20,000 IU vitamin D3 once a week Months 2-6: 10,000 IU vitamin D3 once a week Vitamin D: Daily multivitamin with 400 IU vitamin D.	Placebo plus a multivitamin with 400 IU vitamin D Placebo: Month 1: Placebo once a week Months 2-6: Placebo once a week Vitamin D: Daily multivitamin with 400 IU vitamin D.
Measure Participants	6	2
1-month	182.67	154
3-month	172.67	115.5
6-month	195.17	50.5

Adverse Events

Time Frame	6 months
Adverse Event Reporting Description	Definitions do not differ from those of the ClinicalTrials.gov definitions.
Arm/Group Title	Group 1		Group 2
Arm/Group Description	10,000 IU Vitamin D3 plus a multivitamin with 400 IU vitamin D 10,000 IU Vitamin D3: Month 1: 20,000 IU vitamin D3 once a week Months 2-6: 10,000 IU vitamin D3 once a week Vitamin D: Daily multivitamin with 400 IU vitamin D.		Placebo plus a multivitamin with 400 IU vitamin D Placebo: Month 1: Placebo once a week Months 2-6: Placebo once a week Vitamin D: Daily multivitamin with 400 IU vitamin D.
All Cause Mortality
	Group 1		Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/2 (0%)
Serious Adverse Events
	Group 1		Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Group 1		Group 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/7 (14.3%)		1/2 (50%)
Gastrointestinal disorders
Constipation	1/7 (14.3%)	1	0/2 (0%)	0
Renal and urinary disorders
Infection	0/7 (0%)	0	1/2 (50%)	1
Kidney Stones	1/7 (14.3%)	1	0/2 (0%)	0

Limitations/Caveats

Study enrollment did not reach the required number of subjects; the analysis results would not have been reliable or have enough statistical power. Therefore, samples were not processed and data was not analyzed.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.