Vitamin D Deficiency
Conditions
Keywords
chronic kidney disease mineral and bone disorder, vitamin D2, parathyroid hormone
Brief summary
It is hypothesised that the efficacy and safety of Vitamin D2 soft capsule to treat the Chronic Kidney Disease Mineral and Bone Disease (CKD-MBD) are equal to 1,25(OH)2 Vitamin D3 (Rocaltrol) in the patients with CKD stage 3-5.
Detailed description
This study will enroll chronic kidney disease patients, stage 3 to 5, who have chronic kidney disease mineral and bone disease (CKD-MBD)as defined by Kidney Disease Improvement Global Outcome (KDIGO) Guidelines. Patients in one center will be randomized to receive oral Vitamin D2 soft capsule or Rocaltrol. A total of 200 patients will be enrolled, 100 in the Vitamin D2 group and 100 in the 1,25(OH)2 Vitamin D3 group. Outcomes will be assessed as proportion of patients achieving target blood levels on calcium, phosphorus, parathyroid hormone, and 25 hydroxyvitamin D. Other outcomes will also be assessed, which include secondary hyperparathyroidism (sHPT), vascular calcification, and cardiovascular diseases.
Interventions
DRUGVitamin D2
Treatment with Vit D2.
DRUG1,25(OH)2 Vit D3
Treatment with 1,25(OH)2 Vitamin D3(Rocaltrol).
Sponsors
Beijing Municipal Science & Technology Commission
Dongliang Zhang, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients with age between 18-75 years. * Patients with chronic kidney disease stage 3 to 5, and concurrent chronic kidney disease mineral and bone disorder.
Exclusion criteria
* Renal artery stenosis, inherent renal malformation, solitary kidney, or malignancy in urinary system. * New fracture in last 3 months. * Active system immunity diseases. * History of liver failure * History of intestinal malabsorption or chronic diarrhea * Treatment with phenobarbital, phenytoin, rifampicin, sucralfate, steroids, digoxin, or other medications that could affect vitamin D metabolism * Primary hyperparathyroidism * Treatment with cinacalcet or other calcimimetic within the past 6 months * Anticipated dialysis within 6 months after randomization * Have an unstable medical condition, defined as having been hospitalized within 30 days before screening, the expectation of recurrent hospital admissions or life expectancy of less than 6 months in the judgment of the investigator * Subject is currently enrolled in, or fewer than 30 days have passed since subject has completed another investigational device or drug study(s); or subject is receiving another investigational agent(s). * Current treatment with vitamin D 50,000 IU * Using glucocorticoid or immunosuppressive agents. * Acute renal dysfunction. * The expected live time is less than 2 years. * Pregnant or lactating woman. * Suffered from acute myocardial infraction, acute congestive heart failure, or stroke in last 6 months. * Patients whose concurrent illnesses, disability, or geographical residence would hamper attendance at required study visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Blood Levels of Calcium at the 24th Month of Following up. | 24 months | The blood levels of calcium at the 24th month of following up will be detected. |
| The Blood Levels of Phosphorus at the 24th Month of Following up. | 24 months | The blood levels of phosphorus at the 24th month of following up will be detected. |
| The Blood Levels of Intact Parathyroid Hormone at the 24th Month of Following up. | 24 months | The blood levels of intact parathyroid hormone (iPTH) at the 24th month of following up will be detected. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Blood 25(OH)Vitamin D Level. | 24 months | The levels of blood 25(OH)Vitamin D at the 24th month of following up. |
| The Incidence Rate of Secondary Hyperparathyroidism. | 24 months | Patients with the blood iPTH level higher than 300 pg/ml will be regard as sHPT. The incidence of sHPT during following up were recorded and compared between two groups. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vitamin D2 Patients will be treated by vitamin D2. Oral Vit D2 1.25mg(50,000 unit) once weekly as a start and maintain 1.25mg(50,000 unit) once monthly according to the blood 25(OH)vitamin D level.
Vitamin D2: Treatment with Vit D2. | 104 |
| 1,25(OH)2 Vitamin D3 Patients will be treated by 1,25(OH)2 Vitamin D3. Oral 1,25(OH)2 Vitamin D3(Rocaltrol) by 0.25 microgram once daily at start and regulate the dose according to the changes of blood levels of 25(OH)Vit D, calcium, phosphorus, and intact parathyroid hormone.
1,25(OH)2 Vit D3: Treatment with 1,25(OH)2 Vitamin D3(Rocaltrol). | 100 |
| Total | 204 |
Baseline characteristics
| Characteristic | Total | 1,25(OH)2 Vitamin D3 | Vitamin D2 |
|---|---|---|---|
| 25(OH)Vit D | 15.02 ng/ml STANDARD_DEVIATION 6.83 | 14.90 ng/ml STANDARD_DEVIATION 6.15 | 15.14 ng/ml STANDARD_DEVIATION 7.46 |
| Age, Continuous | 56.89 years STANDARD_DEVIATION 6.76 | 56.27 years STANDARD_DEVIATION 5.94 | 57.35 years STANDARD_DEVIATION 5.64 |
| Ca-baseline | 2.30 mmol/L STANDARD_DEVIATION 0.12 | 2.31 mmol/L STANDARD_DEVIATION 0.11 | 2.29 mmol/L STANDARD_DEVIATION 0.14 |
| iPTH-baseline | 98.2 ng/ml STANDARD_DEVIATION 100.1 | 89.5 ng/ml STANDARD_DEVIATION 75 | 109.7 ng/ml STANDARD_DEVIATION 127.8 |
| P-baseline | 1.14 mmol/L STANDARD_DEVIATION 0.22 | 1.14 mmol/L STANDARD_DEVIATION 0.21 | 1.15 mmol/L STANDARD_DEVIATION 0.24 |
| Region of Enrollment China | 204 participants | 100 participants | 104 participants |
| Sex: Female, Male Female | 64 Participants | 34 Participants | 30 Participants |
| Sex: Female, Male Male | 140 Participants | 66 Participants | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 104 | 8 / 100 |
| serious Total, serious adverse events | 13 / 104 | 10 / 100 |
Outcome results
Primary
The Blood Levels of Calcium at the 24th Month of Following up.
The blood levels of calcium at the 24th month of following up will be detected.
Time frame: 24 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D2 | The Blood Levels of Calcium at the 24th Month of Following up. | 2.31 mmol/L | Standard Deviation 0.14 |
| 1,25(OH)2 Vitamin D3 | The Blood Levels of Calcium at the 24th Month of Following up. | 2.33 mmol/L | Standard Deviation 0.14 |
Comparison: The blood levels of calcium at the 24th month of following up were compared to the levels of the baseline both in group Vitamin D2.p-value: 0.117t-test, 2 sided
Comparison: The blood levels of calcium at the 24th month of following up were compared to the levels of the baseline in group 1,25(OH)2 Vitamin D3.p-value: 0.309t-test, 2 sided
Comparison: The levels of blood calcium at the 24th month of following up were compared between two groups.p-value: 0.554t-test, 2 sided
Primary
The Blood Levels of Intact Parathyroid Hormone at the 24th Month of Following up.
The blood levels of intact parathyroid hormone (iPTH) at the 24th month of following up will be detected.
Time frame: 24 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D2 | The Blood Levels of Intact Parathyroid Hormone at the 24th Month of Following up. | 96.5 pg/ml | Standard Deviation 87.1 |
| 1,25(OH)2 Vitamin D3 | The Blood Levels of Intact Parathyroid Hormone at the 24th Month of Following up. | 108.1 pg/ml | Standard Deviation 134 |
Comparison: The levels of blood iPTH were compared between the 24th month and the baseline in group Vitamin D2.p-value: 0.179t-test, 2 sided
Comparison: The levels of blood iPTH were compared between the 24th month and the baseline group 1,25(OH)2 Vitamin D3, respectively.p-value: 0.106t-test, 2 sided
Comparison: The levels of blood iPTH at the 24th month of following up were compared between two groups.p-value: 0.463t-test, 2 sided
Primary
The Blood Levels of Phosphorus at the 24th Month of Following up.
The blood levels of phosphorus at the 24th month of following up will be detected.
Time frame: 24 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D2 | The Blood Levels of Phosphorus at the 24th Month of Following up. | 1.27 mmol/L | Standard Deviation 0.39 |
| 1,25(OH)2 Vitamin D3 | The Blood Levels of Phosphorus at the 24th Month of Following up. | 1.25 mmol/L | Standard Deviation 0.33 |
Comparison: The levels of blood phosphorus were compared between the 24th month of following up and the baseline in group Vitamin D2.p-value: <0.001t-test, 2 sided
Comparison: The levels of blood phosphorus were compared between the 24th month of following up and the baseline in group 1,25(OH)2 Vitamin D3, respectively.p-value: <0.001t-test, 2 sided
Comparison: The levels of blood phosphorus at the 24th month of following up were compared between two groups.p-value: 0.694t-test, 2 sided
Secondary
The Blood 25(OH)Vitamin D Level.
The levels of blood 25(OH)Vitamin D at the 24th month of following up.
Time frame: 24 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D2 | The Blood 25(OH)Vitamin D Level. | 37.31 ng/ml | Standard Deviation 10.49 |
| 1,25(OH)2 Vitamin D3 | The Blood 25(OH)Vitamin D Level. | 18.07 ng/ml | Standard Deviation 7.55 |
Comparison: The levels of blood 25(OH)Vitamin D were compared between the 24th month and the baseline in group 1,25(OH)2 Vitamin D3.p-value: <0.001t-test, 2 sided
Comparison: The levels of blood 25(OH)Vitamin D were compared between the 24th month and the baseline in group Vitamin D2.p-value: <0.001t-test, 2 sided
Comparison: The levels of blood 25(OH) Vitamin D at the 24th month of following up were compared between two groups.p-value: <0.001t-test, 2 sided
Secondary
The Incidence Rate of Secondary Hyperparathyroidism.
Patients with the blood iPTH level higher than 300 pg/ml will be regard as sHPT. The incidence of sHPT during following up were recorded and compared between two groups.
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vitamin D2 | The Incidence Rate of Secondary Hyperparathyroidism. | 14 participants |
| 1,25(OH)2 Vitamin D3 | The Incidence Rate of Secondary Hyperparathyroidism. | 15 participants |
p-value: 0.753Chi-squared