Clinical trial NCT01265615: Paricalcitol Versus Calcitriol for the Management of Renocardiac Syndrome in Renal Transplant Patients
Official title: Phase 4 Study of Paricalcitol and Calcitriol for Reparative Management of Chronic Allograft Dysfunction and Renocardiac Syndrome in Vitamin D Insufficient Renal Transplant Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cardiorenal Syndrome
Chronic Allograft Nephropathy
Keywords: chronic allograft nephropathy
stem-progenitor cells
cardiorenal syndrome
calcitriol
paricalcitol
cholecalciferol
cardiac repair
renal repair
Lead sponsor: Ural State Medical University
Sponsor class: OTHER
Collaborators: name: Ural Institute of Cardiology
name: De Haar Research Foundation
First posted: 2010-12-23
Enrollment: 109
Sex: MALE
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: We hypothesize that paricalcitol and calcitriol in dose-dependent manner are effective for the management of chronic allograft dysfunction (CAD), protection and repair of kidney and heart, management of chronic renocardiac syndrome (CRS). We assume that paricalcitol can have some advantages if compare with calcitriol or cholecalciferol due to absence of calcemic and phosphatemic complications alongside with great beneficial potential.

Detailed description: Paricalcitol and calcitriol are identically effective for the management of chronic allograft dysfunction (CAD), protection and repair of kidney and heart, management of chronic renocardiac syndrome (CRS). Vitamin D can reduce progression of CAD. Activation of VDR in proximal part of nephron leads to rapid non-genomic beneficial effects with urgent multilevel protection of the most functionally important portion of kidney. Rising expression of VDR in distal portions of nephron stimulates slows genomic effects with some local repair responses.

Hormone D may stimulate recruitment and activity of the different origin stem-progenitor cells (SPCs) with beneficial effects on different stages of regeneration by force of para- and autocrine activity. SPCs are revealing mostly in interstitium and among fibroblast-like cells. Vitamin D did not confirm efficacy as a tool for management of mesenchymal stem cells (MSCs) in human however it needs more research experimental evidences due to multifactorial influence on SPCs in human being including immunosuppressive and bone-marrow-related effects of cyclosporine in kidney transplant (Tx) patients. Paricalcitol and calcitriol can slow down migration and infiltration of MSC into interstitium and vessel wall. The side population of mature and SPCs (first of all, with bone-marrow and mesenchymal phenotype) is the most metabolically and functionally active portion of cells with high sensitivity to vitamin D receptor (VDR) activation that responsible for repair of tissue.

The most optimal scheme of treatment with vitamin D in patients with CAD and CRS is an administration of paricalcitol with dose 2-4 μg daily and supplemental intake of vitamin D including special diet, multivitamins, and others with optimal dose until 1800 international units (IU) but excluding insolation as a factor of skin carcinoma. High-dose medicinal intake of calcitriol (until 6 mcg and higher) showed relatively high efficacy but rather excessive level of complications mediated with mineral metabolism.

Paricalcitol and calcitriol may significantly improve contractility of myocardium and reduce cardiovascular risk, heart failure (HF) and hypertension with some beneficial effects on cardiorenal axis and renin-angiotensin-aldosterone system.

Eligibility criteria: Inclusion Criteria:

* Age 40-75
* Male
* History of chronic kidney disease and cardiorenal syndrome
* Written informed consent

Exclusion Criteria:

* Female
* Acute illness
* Life-threat competitive illness
* Mental disorders
* Endocrinologic diseases (including diabetes mellitus, hyperparathyroidism, and other thyroid disorders)
* Need for dialyses
* Hypercalcemia
* Concomitant use of hormone or cytokine medication
* Participation to any drug-investigation during the previous 60 days as checked with VIP check

Primary outcomes:
measure: CAD (Chronic Allograft Dysfunction) Degree
timeFrame: day 180 after Tx (transplantation)
Secondary outcomes:
measure: Heart Failure (HF)
timeFrame: on day 180 after Tx (transplantation)
measure: GFR (Glomerular Filtration Rate)
timeFrame: on day 180
measure: CAD (Chronic Allograft Dysfunction) Degree
timeFrame: on day 90
measure: Serum Creatinine
timeFrame: on day 180 after Tx
measure: Number of Circulating SP (Side Population) Stem-Progenitor Cells
timeFrame: on day 180
measure: VDR (Vitamin D Receptor) Expression in Myocardium
timeFrame: on day 180
measure: VDR (Vitamin D Receptor) Expression in Kidney
timeFrame: on day 180
measure: Systolic Blood Pressure
timeFrame: on day 180
measure: Coronary Calcium Score
timeFrame: on day 180
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: De Haar Research Foundation
state: South Holland
city: Yekaterinburg
country: Russian Federation
facility: Ural Institute of Cardiology
Study officials:
affiliation: Ural Institute of Cardiology
name: Alexander Kharlamov, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Ural State Medical University
name: Alexander Perrish, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kharlamov AN, Perrish AN, Gabiskii IaL, Ronne Kh, Ivanova EIu. [Vitamin D in the treatment of cardiorenal syndrome in patients with chronic nephropathy]. Kardiologiia. 2012;52(3):33-44. Russian.