Salt Intake and Antiproteinuric Effect of Paricalcitol in Type 2 Diabetes (PROCEED)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Mario Negri Institute for Pharmacological Research
Sponsor:
Collaborator:
Abbott
Information provided by (Responsible Party):
Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier:
NCT01393808
First received: July 12, 2011
Last updated: March 6, 2014
Last verified: March 2014
  Purpose

Proteinuria is an independent risk factor for cardiovascular morbidity and mortality and for renal disease progression. More proteinuria is associated with faster progression, whereas treatments that reduce proteinuria are renoprotective in both diabetic and non diabetic chronic kidney disease. Of note, lower the residual proteinuria achieved by treatment slower is the disease progression in the long term. On the basis of the above findings, proteinuria has become a target of renoprotective therapy.

Among different antihypertensive medications, those that inhibit the Renin Angiotensin System, such as angiotensin converting enzyme (ACE)inhibitors and angiotensin receptor blockers (ARBs), are those that at comparable blood pressure control, more effectively reduce proteinuria and slow renal disease progression. Thus they have become the key component of renoprotective therapy in patients with proteinuric chronic kidney disease. Observational studies found that their effectiveness, however, is limited or even fully blunted in patients who eat large amount of salt.

Experimental evidence indicates a renoprotective role of the vitamin D system in chronic renal disease. A recent randomized, controlled trial, add-on therapy with selective Vitamin D receptor activator paricalcitol showed an additive antiproteinuric effect in subjects with type 2 diabetes and chronic kidney disease on background Renin-angiotensin-system inhibitor therapy. This effect, however, was largely restricted to subjects with daily sodium intake exceeding 12 grams and was negligible in those with lower sodium intake. Thus, treatment with paricalcitol appears to be effective in particular in those patients who do not appreciably benefit of renin angiotensin system (RAS) inhibitors therapy because of high salt intake. Thus, whether the antiproteinuric effect of paricalcitol is modified by concomitant salt intake in patients with chronic kidney disease (CKD) on background RAS inhibitors therapy, is worth investigating.

The broad aim of this study is to evaluate the interaction between paricalcitol therapy and sodium intake in type 2 diabetes patients with proteinuric kidney disease on stable background RAS inhibitor therapy.


Condition Intervention Phase
Type 2 Diabetes
Drug: Paricalcitol
Other: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Prospective, Randomized, Cross-over, Double-blind, Placebo-controlled Study to Assess the Antiproteinuric Effect of Selective Vitamin d Receptor Activation by Paricalcitol in Type 2 Diabetes Patients on Low or High Sodium Diet and Stable Ras Inhibitor Therapy

Resource links provided by NLM:


Further study details as provided by Mario Negri Institute for Pharmacological Research:

Primary Outcome Measures:
  • Changes in urinary albumin excretion from baseline at 4 month. [ Time Frame: At baseline and 1,2,3 and 4 month. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Ambulatory and 24-hour blood pressure profile. [ Time Frame: At 1 month. ] [ Designated as safety issue: No ]
  • Ambulatory and 24-hour blood pressure profile. [ Time Frame: At 2 month. ] [ Designated as safety issue: No ]
  • Ambulatory and 24-hour blood pressure profile. [ Time Frame: At 3 month. ] [ Designated as safety issue: No ]
  • Ambulatory and 24-hour blood pressure profile. [ Time Frame: At 4 month. ] [ Designated as safety issue: No ]

Estimated Enrollment: 112
Study Start Date: September 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Paricalcitol Drug: Paricalcitol
1-month Paricalcitol 2mcg/day
Placebo Comparator: placebo Other: placebo
1-month Placebo Treatment

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female patients;
  • Age > 18 years;
  • Type 2 diabetes patients on low or high sodium diet and stable RAS inhibitor therapy with the following conditions:

Urinary albumin excretion (UAE) rate >300mg/24 hours (200 mcg/min); Serum creatinine <2 mg/dL, PTH ≥ 20 mEq/L and <110 mEq/L; Calcium and phosphorus levels < 9.5 mg/dl and < 5mg/dl, respectively; Controlled BP (systolic/diastolic <140/90 mmHg) while on stable RAS inhibitor therapy;

- Written informed consent.

Exclusion Criteria:

  • Previous Vitamin D or Vitamin D analogs therapy (within 3 months prior to the study entry);
  • Evidence of toxicity to Vitamin D;
  • History of kidney stones;
  • Poorly controlled Diabetes: Hb1Ac > 12%;
  • Therapy with calcitonin, bisphosphonates, cinacalcet, glucocorticoids, immunosuppressive drugs or other drug that may affect calcium or bone metabolism;
  • Cancer and any severe systemic disease or clinical condition that may jeopardize data interpretation or completion of the study;
  • Any clinically relevant conditions that might affect study participation and/or study results;
  • Any contraindication to be exposed to Paricalcitol;
  • Pregnancy or lactating;
  • Women of childbearing potential without following a scientifically accepted form of contraception;
  • Legal incapacity.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01393808

Contacts
Contact: Piero Ruggenenti, MD 0039 035 45351 piero.ruggenenti@marionegri.it

Locations
Italy
ASL of Ponte San Pietro - Diabetologic Unit Recruiting
Brembate, Bergamo, Italy, 24030
Contact: Antonio Belviso, MD    0039/035/603449      
Clinical Research Center fo Rare Diseases Aldo and Cele Daccò Recruiting
Ranica, Bergamo, Italy, 24020
Contact: Piero Ruggenenti, MD    0039 035 453531    piero.ruggenenti@marionegri.it   
Sub-Investigator: Matias Trillini, MD         
Principal Investigator: Norberto Perico, MD         
Azienda Ospedaliera di Treviglio e Caravaggio - Unit of Diabetology and Metabolic Diseases Recruiting
Romano di Lombardia, BG, Italy
Contact: Antonio Bossi, MD         
Principal Investigator: Antonio Bossi, MD         
Sub-Investigator: Ilian Iliev, MD         
Azienda Ospedaliera Bolognini - Unità di Medicina Recruiting
Seriate, BG, Italy
Contact: Ruggero Mangili, MD         
Principal Investigator: Ruggero Mangili, MD         
Azienda Ospedaliera di Treviglio e Caravaggio - Unit of Diabetology and Metabolic Diseases Recruiting
Treviglio, BG, Italy
Contact: Antonio Bossi, MD         
Principal Investigator: Antonio Bossi, MD         
Sub-Investigator: Anelija Parvanova Ilieva, MD         
Azienda Ospedaliera Ospedali Riuniti di Bergamo Recruiting
Bergamo, Italy
Contact: Roberto Trevisan, MD         
Principal Investigator: Roberto Trevisan, MD         
Sponsors and Collaborators
Mario Negri Institute for Pharmacological Research
Abbott
  More Information

No publications provided

Responsible Party: Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier: NCT01393808     History of Changes
Other Study ID Numbers: PROCEED, 2011-001713-14
Study First Received: July 12, 2011
Last Updated: March 6, 2014
Health Authority: Italy: Ministry of Health

Keywords provided by Mario Negri Institute for Pharmacological Research:
Type 2 diabetes
Paricalcitol
Proteinuria
Sodium intake

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Ergocalciferols
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on September 16, 2014