Chronic Kidney Disease
Conditions
Keywords
paricalcitol, chronic kidney disease, cardiac hypertrophy
Brief summary
The purpose of this study is to test the hypothesis that selective vitamin D receptor activation reduces left ventricular hypertrophy and ameliorates inflammation and atherosclerosis in stage 3 -5 chronic kidney disease.
Detailed description
Cardiovascular disease is the leading cause of mortality and morbidity in patients with chronic kidney disease. According to a previous study, only 15.6% of the patients beginning dialysis therapy had a normal echocardiogram, with left ventricular hypertrophy, left ventricular dilatation and systolic dysfunction occurring in 40.7%, 28% and 15.6% of patients, respectively. In addition, these patients are at an accelerated risk of developing atherosclerosis. The Kidney Disease Outcome Quality Initiative guideline recently raised concerns of a high prevalence of vitamin D deficiency in chronic kidney disease patients not yet requiring dialysis treatment. In addition, very recent data suggested that vitamin D deficiency is an important predictor of mortality in end-stage renal disease patients. Furthermore, hemodialysis patients treated with paricalcitol, a selective vitamin D receptor activator, showed a significantly lower risk of cardiovascular death than those not receiving vitamin D therapy. A number of studies also showed positive benefit of vitamin D receptor activator treatment on regression of left ventricular hypertrophy in dialysis patients. However, there is so far no data in patients with stage 3 and 4 chronic kidney disease where a high prevalence of vitamin D deficiency and cardiac hypertrophy has been reported.
Interventions
DRUGparicalcitol
oral paricalcitol capsule 1 microgram once daily if iPTH \<500pg/mL or 2 microgram once daily if iPTH \>=500pg/mL. Thereafter, dose titration in 1 microgram decrement will be done based on safety reasons (that is, for low PTH or high calcium and phosphorus level). The duration of treatment will be for 1 year.
Sponsors
Abbott
The University of Hong Kong
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patient with stage 3 -5 chronic kidney disease (that is, eGFR \< 60 ml/min per 1.73m2) diagnosed for more than 2 months and not expected to start dialysis within the next 12 months, and * Patient with screening echocardiography showing evidence of left ventricular hypertrophy * Patient has not received vitamin D therapy in the previous 4 weeks * For entry into the Treatment Phase, the subject must have: * screening iPTH \>= 55 pg/ml or 5.8pmol/L (determined by the Nichols second-generation assay or similar assay) * serum calcium \< 10.2 mg/dL (2.55 mmol/L) * serum phosphorus =\< 5.2mg/dL (1.68mmol/L) * Ca\*P product \< 54 mg2/dL2 (4.36mmol2/L2) * If female, subject is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), or is of childbearing potential and practicing birth control measures. * Patients who provide informed consent for the study
Exclusion criteria
* Patient with a history of an allergic reaction or significant sensitivity to vitamin D or vitamin D related compounds. * Patient with history of renal stones * Patient with current malignancy * Patients with clinically significant gastrointestinal disease or liver disease * Patient with acute renal failure in the recent three months * Patient with a history of drug or alcohol abuse within six months prior to the screening phase * Patient is known to be human immunodeficiency virus (HIV) positive. * Patient with evidence of poor compliance with diet and medication. * Patient currently receiving medications that may affect calcium, phosphorus metabolism such as calcitonin, cinacalcet, bisphophonates or vitamin D compounds (other than study drug), or other drugs that may affect calcium or bone metabolism, other than females on stable estrogen and/or progestin therapy. * Patients with active granulomatous disease * Patient with pregnancy * Patients currently receiving glucocorticoid steroid or other immunosuppressive treatment or had been administered glucocorticoid or other immunosuppressive treatment for more than 14 days within recent 6 months. * Patients with contraindication for MRI examination
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in left ventricular mass index determined by MRI | 1 year |
Secondary
| Measure | Time frame |
|---|---|
| Change in left atrial and ventricular volumes, systolic and diastolic function, carotid intima-media thickness, flow mediated dilation, pulse wave velocity, serum inflammatory and cardiac biomarkers, intact PTH, 24-hour urine protein and renal function | 1 year |
Countries
Hong Kong
Outcome results
None listed