Vitamin D Repletion in Primary Hyperparathyroidism

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Randomized Controlled Trial of Vitamin D Repletion Regimens in Primary Hyperparathyroidism

Conditions
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Primary Hyperparathyroidism, Vitamin D Deficiency

Intervention / Treatment
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* Drug: 10,000 IU Vitamin D3
* Other: Placebo
* Dietary Supplement: Vitamin D


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Areal Bone Mineral Density of the Lumbar Spine | Measured by dual-energy x-ray absorptiometry (DEXA) scan | 6 months | 
| Trabecular Bone Density at the Forearm | Measured by high resolution peripheral quantitative computed tomography | 6 months | 
| Change in Urinary Calcium Level | This is designed to measure how the study treatment will affect urinary calcium level over time. | 1 month, 3 months, 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endocrinology, Metabolic Bone Disease, Primary Hyperparathyroidism, PHPT, Vitamin D Deficiency, Bone Mineral Density, Hyper-calcemia