Primary Hyperparathyroidism, Vitamin D Deficiency
Conditions
Keywords
Endocrinology, Metabolic Bone Disease, Primary Hyperparathyroidism, PHPT, Vitamin D Deficiency, Bone Mineral Density, Hyper-calcemia
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.
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.
Interventions
DRUG10,000 IU Vitamin D3
Month 1: 20,000 IU vitamin D3 once a week Months 2-6: 10,000 IU vitamin D3 once a week
OTHERPlacebo
Month 1: Placebo once a week Months 2-6: Placebo once a week
DIETARY_SUPPLEMENTVitamin D
Daily multivitamin with 400 IU vitamin D.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Columbia University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Patient, investigator and study team will be blinded to study arm ramdomization.
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Parathyroid Hormone (PTH) Level | 6 months | This is designed to measure how many participants will achieve PTH \> 65 pg/mL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Trabecular Bone Density at the Forearm | 6 months | Measured by high resolution peripheral quantitative computed tomography |
| 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. |
| Areal Bone Mineral Density of the Lumbar Spine | 6 months | Measured by dual-energy x-ray absorptiometry (DEXA) scan |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 10,000 IU Vitamin D3 + Multivitamin 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. | 7 |
| Placebo + Multivitamin 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. | 2 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | 10,000 IU Vitamin D3 + Multivitamin | Placebo + Multivitamin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 1 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 2 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 7 Participants | 2 Participants | 9 Participants |
| Sex: Female, Male Female | 6 Participants | 2 Participants | 8 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 2 |
| other Total, other adverse events | 1 / 7 | 1 / 2 |
| serious Total, serious adverse events | 0 / 7 | 0 / 2 |
Outcome results
Primary
Serum Parathyroid Hormone (PTH) Level
This is designed to measure how many participants will achieve PTH \> 65 pg/mL.
Time frame: 6 months
Population: 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.
Secondary
Areal Bone Mineral Density of the Lumbar Spine
Measured by dual-energy x-ray absorptiometry (DEXA) scan
Time frame: 6 months
Population: Study enrollment did not reach the required number of subjects; the analysis results are not reliable or have enough statistical power.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 10,000 IU Vitamin D3 + Multivitamin | Areal Bone Mineral Density of the Lumbar Spine | -.98777 percentage of change | Standard Deviation 1.662643 |
| Placebo + Multivitamin | Areal Bone Mineral Density of the Lumbar Spine | 1.442861 percentage of change | Standard Deviation 4.376592 |
Secondary
Change in Urinary Calcium Level
This is designed to measure how the study treatment will affect urinary calcium level over time.
Time frame: 1 month, 3 months, 6 months
Population: 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 | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 10,000 IU Vitamin D3 + Multivitamin | Change in Urinary Calcium Level | 1-month | 182.67 mg/day |
| 10,000 IU Vitamin D3 + Multivitamin | Change in Urinary Calcium Level | 3-month | 172.67 mg/day |
| 10,000 IU Vitamin D3 + Multivitamin | Change in Urinary Calcium Level | 6-month | 195.17 mg/day |
| Placebo + Multivitamin | Change in Urinary Calcium Level | 1-month | 154 mg/day |
| Placebo + Multivitamin | Change in Urinary Calcium Level | 3-month | 115.5 mg/day |
| Placebo + Multivitamin | Change in Urinary Calcium Level | 6-month | 50.5 mg/day |
Secondary
Trabecular Bone Density at the Forearm
Measured by high resolution peripheral quantitative computed tomography
Time frame: 6 months
Population: Study enrollment did not reach the required number of subjects; the analysis results are not reliable nor have enough statistical power.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 10,000 IU Vitamin D3 + Multivitamin | Trabecular Bone Density at the Forearm | -1.00345 percentage of change | Standard Deviation 3.912386 |
| Placebo + Multivitamin | Trabecular Bone Density at the Forearm | -2.59816 percentage of change | Standard Deviation 0.583978 |