Renal Osteodystrophy
Conditions
Keywords
kidney, parathyroid hormone, vitamin d
Brief summary
The majority of patients with moderate to severe chronic kidney disease (CKD) (stages 3 and 4) develop secondary hyperparathyroidism (2°HPT), but the optimal therapy to control hyperparathyroidism in this group is unknown. The National Kidney Foundation presented guidelines in 2003 recommending vitamin D supplementation for vitamin D insufficient patients and active vitamin D therapy in patients with sufficient levels. These guidelines are based on opinion since there are no significant trials to determine if vitamin D supplementation is effective in this population. The active vitamin D metabolites doxercalciferol, paricalcitol, and calcitriol have been shown to effectively suppress parathyroid hormone (PTH), but have not been compared with vitamin D supplementation with a calciferol (ergocalciferol or cholecalciferol). Beyond hyperparathyroidism, small studies suggest vitamin D replacement in vitamin D insufficient non-CKD subjects result in improved pain, feeling of well being, blood pressure and strength. In this proposed study we wish to directly compare the effectiveness of cholecalciferol versus doxercalciferol in suppressing elevated PTH levels in subjects with CKD not on dialysis who have vitamin D insufficiency in a three month study. Secondary endpoints will be change in blood pressure.
Detailed description
Patients with CKD stage 3 were randomly allocated (by blinded group allocation) to either cholecalciferol (4000 U per day for one month then 2000 IU daily thereafter) or doxercalciferol (2.5 mcg po daily. Assessments for blood endpoints (primary end point PTH; secondary calcium, phosphorus) were done monthly. Other assessments (blood pressure) were done at baseline and at 3 months.
Interventions
DRUGdoxercalciferol
form of vitamin D that is already in active form.
DRUGCholecalciferol
from of vitamin D that requires cells in the body to make active
Sponsors
Indiana University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 82 Years
Healthy volunteers
No
Inclusion criteria
* age 18 years old or older, male or female * able to sign informed consent * CKD stage 3 (GFR 30-59 ml/min) or stage 4 (15-29 ml/min) * intact Parathyroid hormone level (iPTH) \> 100 pg/ml for stage 3 or iPTH \> 150 pg/ml for stage 4 * calcidiol levels ≤ 20 ng/ml * ability to ambulate without assistance
Exclusion criteria
* intact PTH \> 400 pg/ml * initial corrected Calcium \> 9.7 mg/dl * initial serum Phosphorous \> 5.0 mg/dl * initial standardized blood pressure of \> 160/100 * history of significant liver disease or cirrhosis * anticipated requirement for dialysis in 6 months * malabsorption, severe chronic diarrhea, or ileostomy * no calcimimetic or active vitamin D therapy 30 days prior to enrollment * use of digoxin, magnesium containing products, mineral oil, or cholestyramine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Reduction in PTH | 3 month | Percent reduction in PTH from baseline to 3 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Systolic Blood Pressure at 3 Months | 3 month | systolic blood pressure at 3 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Doxercalciferol, Active Vitamin D Doxercalciferol is an active Vitamin D readily usable by human body. | 25 |
| Cholecalciferol, Inactive Vitamin D Cholecalciferol is inactive Vitamin D and requires the kidneys to make it active. | 22 |
| Total | 47 |
Baseline characteristics
| Characteristic | Doxercalciferol, Active Vitamin D | Cholecalciferol, Inactive Vitamin D | Total |
|---|---|---|---|
| Age, Continuous | 65 years STANDARD_DEVIATION 10 | 62 years STANDARD_DEVIATION 10 | 63.5 years STANDARD_DEVIATION 10 |
| Region of Enrollment United States | 25 participants | 22 participants | 47 participants |
| Sex: Female, Male Female | 9 Participants | 12 Participants | 21 Participants |
| Sex: Female, Male Male | 16 Participants | 10 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 25 | 0 / 22 |
| serious Total, serious adverse events | 0 / 25 | 0 / 22 |
Outcome results
Primary
Percent Reduction in PTH
Percent reduction in PTH from baseline to 3 months
Time frame: 3 month
Population: The initial sample size was based on the published response to doxercalciferol versus placebo where a 46% reduction in PTH was observed over 6 months, with a 51% SD. The expected reduction in PTH with cholecalciferol was based on the best-case scenario decrease of 17.8% in PTH with ergocalciferol from our own clinic setting.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Doxercalciferol, Active Vitamin D | Percent Reduction in PTH | 27 % change in PTH baseline to 3 months | Standard Deviation 34 |
| Cholecalciferol, Inactive Vitamin D | Percent Reduction in PTH | 10 % change in PTH baseline to 3 months | Standard Deviation 31 |
Secondary
Systolic Blood Pressure at 3 Months
systolic blood pressure at 3 months
Time frame: 3 month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Doxercalciferol, Active Vitamin D | Systolic Blood Pressure at 3 Months | 120 mmHg | Standard Deviation 47 |
| Cholecalciferol, Inactive Vitamin D | Systolic Blood Pressure at 3 Months | 128 mmHg | Standard Deviation 33 |