Primary Hyperparathyroidism (PHPT): Early Effect of Vitamin D
Primary hyperparathyroidism (PHPT) is a common disease that occurs in 1 in 10,000 people every year. In the presence of this condition, the parathyroid glands produce excessive amounts of parathyroid hormone (PTH), which regulates calcium levels. The high levels of parathyroid hormone remove too much calcium from bones, and then deposit the excess calcium in the blood, which is then filtered into the urine by the kidneys. Bone health is threatened by excess calcium loss which weakens bone structure. Other affected organs include the skeleton (calcium loss leads to a "weakening" of the skeleton), and the kidneys (high blood calcium can lead to kidney stones).
It is now evident that the majority of patients with even mild Primary Hyperparathyroidism are vitamin D deficient. In 2009, new international guidelines for the management of asymptomatic PHPT direct physicians to measure 25-hydroxyvitamin D (D3 or 25-OHD) in all patients, and to replete the reserve of vitamin D when the level is low (< 20 ng/ml). However, no recommendations for vitamin D repletion are given, because of limited data regarding the effects of vitamin D repletion, appropriate dosing and safety. Therefore, there is an urgent need for data upon which to base such recommendations, as well as are data on the effects of such treatment upon bones.
Subjects with low vitamin D3 levels will be selected for this trial. They will be given enough vitamin D3 to raise their low blood levels from a low to a normal range. The assessments in this study, including the quadruple label bone biopsy, will allow us to document the short term effects of administering vitamin D3 on changes in bone.
All participants enrolled in this trial will be vitamin D3 deficient. Participants will take an antibiotic (tetracycline) 4 times a day to mark the starting point from which bone changes will be assessed. After 3 days of tetracycline, a 12 week course of vitamin D3 or placebo will be initiated. Six of 7 participants will receive the study drug (active vitamin D3), while 1 in 7 will receive a placebo (sugar pill). Ten weeks later, another 3-day course of tetracycline will be given. At the end of 12 weeks, a bone biopsy will be done. A small piece of bone (about the size of a pencil eraser) will be removed from the hip (iliac crest). The bone will be analyzed to determine the effect of vitamin D3 on primary hyperparathyroidism.
There will be 4 study visits: Screening, Baseline, Week 8, and Week 12 when the bone biopsy will be performed.
Medical and Social History
Blood tests (drawn at the study center and local Quest Lab)
24-Hour urine collection for calcium and creatinine excretion
Abdominal X-ray (to assess for kidney stones)
Transiliac crest Bone Biopsy
|Primary Hyperparathyroidism Hypercalcemia Vitamin D Deficiency Osteoporosis Osteopenia||Dietary Supplement: Placebo Dietary Supplement: Vitamin D3||Phase 2 Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
|Official Title:||Early Effect of Vitamin D in Primary Hyperparathyroidism|
- Change in Bone Formation Rate (BFR) [ Time Frame: 12 Weeks ]A between group (vitamin D3 vs. placebo) comparison of BFR will be performed at three surfaces, cancellous, intra- and endo-cortical.
|Study Start Date:||May 2010|
|Study Completion Date:||January 2015|
|Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
|Experimental: 50,000 IU Vitamin D3||
Dietary Supplement: Vitamin D3
50,000 IU/week for 8 weeks
Subjects with D3 less than 30 ng/ml: 50,000 IU/week for 4 weeks.
Subjects with D3 25-OHD at or above 30 ng/ml: 50,000 IU/every 2 weeks for 4 weeks.
|Placebo Comparator: Placebo (inactive Vitamin D3)||
Dietary Supplement: Placebo
Subjects will receive placebo vitamin D3, 1 pill weekly for 12 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01329666
|United States, New York|
|Columbia University Medical Center|
|New York, New York, United States, 10032|
|Principal Investigator:||Shonni J. Silverberg, MD||Columbia University|