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Cardiorenal SyndromePhase 4NCT01265615

Paricalcitol Versus Calcitriol for the Management of Renocardiac Syndrome in Renal Transplant Patients

A Phase 4 study testing Paricalcitol, Calcitriol and Cholecalciferol in people with Cardiorenal Syndrome and Chronic Allograft Nephropathy, run by Ural State Medical University at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 40 to 75 years, men only
What is being tested?
Paricalcitol, Calcitriol and Cholecalciferol
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
109 participants
Where
2 sitesin 2 countries
Study dates
Oct 2009to Sep 2010
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 75 years
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • Female
  • Acute illness
  • Life-threat competitive illness
  • Mental disorders
  • Endocrinologic diseases (including diabetes mellitus, hyperparathyroidism, and other thyroid disorders)
  • Need for dialyses
Show all 9Show fewer
  • Hypercalcemia
  • Concomitant use of hormone or cytokine medication
  • Participation to any drug-investigation during the previous 60 days as checked with VIP check

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Netherlands1 site

  • De Haar Research Foundation

    Rotterdam, South Holland, 3071PR

Other trials in Netherlands

Russia1 site

  • Ural Institute of Cardiology

    Yekaterinburg, 620144

Other trials in Russia

About this study

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

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.

Read the 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.

Being tested
Paricalcitol, Calcitriol, Cholecalciferol, Supplemental
Keywords
chronic allograft nephropathy, stem-progenitor cells, cardiorenal syndrome, calcitriol, paricalcitol, cholecalciferol, cardiac repair, renal repair
Medical subject headings
Cardio-Renal Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ParicalcitolDrug

    Also called Zemplar

    paricalcitol group (6-8 μg daily per os - orally - without special diet)

  • CalcitriolDrug

    Also called Rocaltrol

    calcitriol group (2-4 μg daily orally under with dietary restrictions of vitamin D)

  • CholecalciferolDrug

    Also called Fosamax

    cholecalciferol group (intake of cholecalciferol with recommended daily allowance equals 1200-2400 IU per day)

  • SupplementalDietary supplement

    Also called Diet, sun, multivitamin drugs, food

    intake of cholecalciferol in food and multivitamins, less than 400-900 IU per day

Study groups in NCT01265615
Study groupRoleWhat they receive
Paricalcitol treatmentActive comparator6-8 μg daily per os (orally) without special diet
Receives: Drug: Paricalcitol
Calcitriol treatmentActive comparator2-4 μg daily orally under with dietary restrictions of vitamin D
Receives: Drug: Calcitriol
CholecalciferolActive comparatoralendronate sodium/ cholecalciferol capsules with recommended daily allowance equals 1200-2400 IU per day
Receives: Drug: Cholecalciferol
SupplementalOtherintake of cholecalciferol in food and multivitamins, less than 400-900 IU per day
Receives: Dietary Supplement: Supplemental

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. CAD (Chronic Allograft Dysfunction) Degree

    Beyond 180 days, chronic allograft dysfunction (CAD) was characterized by mean Banff degree (revised 2005/2007 criteria) with the data of renal biopsy material. Renal tissue was recovered during routined biopsy. We assessed antibody-mediated rejection, borderline changes, T-cell-mediated rejection, interstitial fibrosis and tubular atropthy, and other changes. Grades:

    Grade I. Mild interstitial fibrosis and tubular atrophy (<25% of cortical area) II. Moderate (26-50%) III. Severe (>50%) (may include non-specific vascular and glomerular sclerosis)

    Measured: day 180 after Tx (transplantation)

Secondary outcomes (9)

  1. Heart Failure (HF)

    NYHA (New York Heart Association) functional class verified with veloergometry probe and by NYHA clinical classification NYHA Class Symptoms I No symptoms and no limitation in ordinary physical activity, e.g. shortness of breath when walking, climbing stairs etc.

    II Mild symptoms and slight limitation during ordinary activity. III Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20-100 m).

    Comfortable only at rest. IV Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients.

    Measured: on day 180 after Tx (transplantation)

  2. GFR (Glomerular Filtration Rate)

    Estimated glomerular filtration rate (eGFR) was calculated using the abbreviated form of the Modification of Diet in Renal Disease (MDRD) study equation: eGFR = exp (5.228 - 1.154 × ln (serum creatinine) - 0.203 × ln (age). Concerning of GFR with Tc99m DTPA renography was used for the complex analysis of renal function. Camera based GFR estimated from Tc99m DTPA renography was named Gates GFR.

    Measured: on day 180

  3. CAD (Chronic Allograft Dysfunction) Degree

    CAD degree measured by Banff score after routine renal biopsy (revised 2005/2007 criteria). We assessed antibody-mediated rejection, borderline changes, T-cell-mediated rejection, interstitial fibrosis and tubular atropthy, and other changes. Grades:

    Grade I. Mild interstitial fibrosis and tubular atrophy (<25% of cortical area) II. Moderate (26-50%) III. Severe (>50%) (may include non-specific vascular and glomerular sclerosis)

    Measured: on day 90

  4. Serum Creatinine

    After an overnight fast, plasma concentrations of hemoglobin, creatinine, cholesterol, glucose, total calcium, and phosphate were measured using an autoanalyzer as described by Adorini L. (2005)

    Measured: on day 180 after Tx

  5. Number of Circulating SP (Side Population) Stem-Progenitor Cells

    Renal cells and solid tissue were obtained from the normal portion of cortex obtained from surgically removed kidneys or by standart biopsy on day 180. Cytofluorimetric analysis and immunofluorescence were performed as described by Oliver J.A. (2004). Sorting and analysis of different cells was done on a FACS (fluorescent activated cell sorting) and by flow cytometry. Cells were analyzed with EPICS systems (Beckman Coulter). Quantification of mRNA expression was achieved using Assays-on-Demand gene expression kits and the ABI PRISM 7000 Sequence Detection System (Applied Biosystem).

    Measured: on day 180

  6. VDR (Vitamin D Receptor) Expression in Myocardium

    VDR content was determined by using an ELISA developed in this laboratory. The protein concentration of the homogenates was determined by the method of Bradford (1976), using BSA as a standard.

    Measured: on day 180

  7. VDR (Vitamin D Receptor) Expression in Kidney

    VDR content was determined by using an ELISA developed in this laboratory. The protein concentration of the homogenates was determined by the method of Bradford (1976), using BSA as a standard.

    Measured: on day 180

  8. Systolic Blood Pressure

    SBP measured by routine method

    Measured: on day 180

  9. Coronary Calcium Score

    Bone mineral density assessed by dual-energy X-ray absorptiometry (DXA) of the whole body, lumbar spine and hip was performed using Hologic scanners (QDR 1000W or QDR 2000). The total Agatston coronary calcium score (CCS) was measured as the sum of calcified plaque scores of all the coronary arteries. The amount of calcium present in the coronary arteries is scored according to the Agatson scale, as follows: 0 - no identifiable disease; 1 to 99 - mild disease; 100 to 399 - moderate disease; 400 or higher - severe disease.

    Measured: on day 180

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Dec 2010 (estimated)
  2. Study startOct 2009
  3. Primary completionApr 2010
  4. Study completionSep 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
109 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01265615
Sponsor's protocol ID
VDCRS03
Status last verified
May 2015
First submitted
22 Dec 2010
Last updated
9 Jun 2015
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 22839442

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Paricalcitol, Calcitriol and Cholecalciferol in people with Cardiorenal Syndrome and Chronic Allograft Nephropathy, run by Ural State Medical University at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Netherlands, Russia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Jun 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

CAD (Chronic Allograft Dysfunction) Degree (time frame: day 180 after Tx (transplantation)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01265615, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2015.

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