Chronic Kidney Disease, Endothelial Dysfunction, Hypertension, Inflammation
Conditions
Keywords
Chronic Kidney Disease, Endothelial dysfunction, Inflammation, Hypertension, paricalcitol, Blood pressure, Vitamin D, Glomerular filtration rate
Brief summary
The study is about possible protective effects of paricalcitol (Zemplar) upon inflammation, blood pressure and kidney function. Kidney Inflammation occurs when white blood cells become abnormally stimulated and accumulate in the kidney and cause damage to the kidney. The purpose of this study is to determine if paricalcitol helps improve kidney injury, blood pressure control and kidney function in patients with chronic kidney disease. The study will last about 7 weeks and involves about 8 visits to the medical center.
Detailed description
We hypothesize that use of paricalcitol in patients with chronic kidney disease will lead to improvement in oxidative stress, inflammation, endothelial function and subsequently ambulatory blood pressures and glomerular filtration rate. We will pursue our hypothesis by the three specific aims: Aim 1: To compare oxidative stress markers in patients treated with paricalcitol before and after the study. Aim 2: To measure endothelial function by flow mediated dilation in patients with chronic kidney disease before and after paricalcitol. Aim 3: To measure actigraphy guided ambulatory blood pressure and GFR in the absence of changes in anti-hypertensive medications in patients with chronic kidney disease. The study will be double blind randomized pilot trial in 24 patients with chronic kidney disease with 1:1:1 allocation to paricalcitol 1 microgram: paricalcitol 2 microgram: Placebo.
Interventions
DRUGparicalcitol
1 mcg or 2 mcg for 4 weeks.
DRUGPlacebo
Placebo
Sponsors
Abbott
Indiana University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with chronic kidney disease with estimated GFR of 30 mL/minute or more. * Patients receiving stable dose of ACE inhibitor or Angiotensin receptor blockers for at least one month. * Patients not currently hypertensive more than 180/110 mmHg by clinic blood pressure. * Hemoglobulin A1C\< 11%
Exclusion criteria
* Patients taking vitamin D analogs * Calcium\> 10 mg/dL * Phosphorus\>6 mg/dL * Patients with anticipated need of dialysis in the next 6 weeks * Patients unstable in the opinion of the investigator * Patients who have emergent need for starting IV iron * Patients who will be started on statins within the next 6 weeks * Patients currently taking PDE5 inhibitors * Patients allergic to radiocontrast, Zemplar or who can not take nitroglycerin * Patients known to be HIV positive * Patients who can not give informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Anti-Inflammatory Effects of Paricalcitol | 6 weeks | change in hsCRP level from baseline to 4 weeks |
| Endothelial Protectant Effects of Paricalcitol | 6 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Effect of Paricalcitol on Hypertension | 6 weeks |
| Effect of Paricalcitol on Kidney Function | 6 weeks |
Countries
United States
Participant flow
Recruitment details
169 patients screened from renal speciality clinics from November 2006 to June 2007
Participants by arm
| Arm | Count |
|---|---|
| 1 1 mcg paricalcitol | 8 |
| 2 2 mcg paricalcitol | 8 |
| 3 Placebo | 8 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | 2 | 3 | 1 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0.0 Participants |
| Age, Categorical >=65 years | 6 Participants | 3 Participants | 7 Participants | 16.0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 5 Participants | 1 Participants | 8.0 Participants |
| Age Continuous | 67.5 years STANDARD_DEVIATION 9.1 | 68.4 years STANDARD_DEVIATION 12.4 | 72.6 years STANDARD_DEVIATION 9.1 | 68.4 years STANDARD_DEVIATION 10.3 |
| Region of Enrollment United States | 8 participants | 8 participants | 8 participants | 24.0 participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 2 Participants | 4.0 Participants |
| Sex: Female, Male Male | 6 Participants | 8 Participants | 6 Participants | 20.0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | — / — | — / — | — / — |
| serious Total, serious adverse events | — / — | — / — | — / — |
Outcome results
Primary
Anti-Inflammatory Effects of Paricalcitol
change in hsCRP level from baseline to 4 weeks
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 1 | Anti-Inflammatory Effects of Paricalcitol | .8 micrograms |
| 2 | Anti-Inflammatory Effects of Paricalcitol | .5 micrograms |
| 3 | Anti-Inflammatory Effects of Paricalcitol | 1.5 micrograms |
Primary
Endothelial Protectant Effects of Paricalcitol
Time frame: 6 weeks
Secondary
Effect of Paricalcitol on Hypertension
Time frame: 6 weeks
Secondary
Effect of Paricalcitol on Kidney Function
Time frame: 6 weeks