Hyperparathyroidism, Secondary
Conditions
Brief summary
Patients with kidney failure on dialysis can be successfully transplanted. However, many of them do not attain a normal kidney function and/or present a slow deterioration of kidney function after transplantation. As a consequence, they can develop an endocrine disorder called hyperparathyroidism, which can cause bone disease and a high risk of bone fractures. In spite of the known bone disease and hyperparathyroidism, there is no well defined treatment for these patients. Moreover, kidney transplant recipients present a higher mortality rate compared to the general population, and the principal cause of death is cardiovascular disease. Dialysis patients are known to have extensive cardiovascular calcifications and increased vascular stiffness, and these factors have been closely associated with cardiovascular mortality. The effect of vitamin D on bone health is well known in the general population. Many studies showed a reduction in fracture rate in post-menopausal women and older men receiving vitamin D and calcium supplements. Vitamin D analogues are also commonly used to treat hyperparathyroidism in dialysis patients. Finally, vitamin D has been suggested to have beneficial effects on the cardiovascular system and to reduce mortality in dialysis patients. Hectorol® is a vitamin D analog which has been demonstrated to effectively treat hyperparathyroidism in dialysis and pre-dialysis patients. The effects of vitamin D supplementation on bone disease, hyperparathyroidism and cardiovascular function in kidney transplant recipients have not been properly studied. Whether Hectorol® therapy helps reducing the severity of bone disease and improving vascular function in kidney transplant recipients is still unknown.
Detailed description
The investigators plan to study the cardiovascular and bone effects of Hectorol® in 100 kidney transplant recipients. The kidney transplant patients will be screened for kidney transplant dysfunction and hyperparathyroidism. The study medication will be given to 50 patients. The other 50 patients will continue to be treated with the actual standard of care at the transplant clinic. Subjects will be followed for 18 months and their laboratory values, bone density, vascular calcification and stiffness will be collected to see if there is an effect of Hectorol® compared to the actual standard of care.
Interventions
DRUGdoxercalciferol
The study drug dosage will be initiated according to baseline iPTH levels. For patients with iPTH\>300 pg/ml, oral Doxercalciferol will be given at 1 mcg/day; for patients with iPTH \<300 pg/ml, oral Doxercalciferol will be initiated at 0.5 mcg/day.
Sponsors
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Kidney transplant recipient \> 18 year/old with reduced and stable kidney function (estimated GFR 25-60 ml/min/1.73m2) * iPTH levels between 120 and 500 pg/ml * Stable immunosuppressive therapy (5-10 mg Prednisone/day, stable dosage of calcineurin inhibitors, or other immunosuppressive agents for at least 6 months)
Exclusion criteria
* Recent rejection episode (\< 3 months) * One of the following: baseline estimated GFR\>60 ml/min/1.73m2 or \<25 ml/min/1.73m2, albumin-corrected Ca\>9.5 mg/dl or serum phosphorus \>4.6 mg/dl. * Recipients of dual transplant organs with exception of kidney-pancreas * Patients already receiving treatment with Vitamin D analogues * Severe peripheral vascular disease or coronary artery disease * History of previous parathyroidectomy * Current alcohol or drug abuse * Pregnant or nursing woman or female of child-bearing age not receiving contraception * Other comorbidities that in the opinion of the investigators would reduce expected patient's survival and preclude study completion * Medications that could interfere with Hectorol® metabolism
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With 50% Reduction of Intact Parathyroid Hormone (iPTH) Levels | 18 months | Number of participants that have 50% reduction in iPTH levels (but not lower than 65 pg/ml) at 18 months |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled from July 2008 to February 2009
Pre-assignment details
Four of the 12 subjects that were consented were withdrawn because they did not meet inclusion criteria or met exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Doxercalciferol Stable kidney transplant recipients will receive Doxercalciferol. The drug dosage will be initiated according to baseline iPTH levels. For patients with iPTH\>300 pg/ml, oral Doxercalciferol will be given at 1 mcg/day; for patients with iPTH \<300 pg/ml, oral Doxercalciferol will be initiated at 0.5 mcg/day. | 4 |
| Control Stable kidney transplant recipients do not receive any drug | 4 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol terminated | 4 | 4 |
Baseline characteristics
| Characteristic | Doxercalciferol | Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 4 | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 |
Outcome results
Primary
Number of Subjects With 50% Reduction of Intact Parathyroid Hormone (iPTH) Levels
Number of participants that have 50% reduction in iPTH levels (but not lower than 65 pg/ml) at 18 months
Time frame: 18 months
Population: Data not analyzed due to study termination