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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01393808
Recruitment Status : Completed
First Posted : July 13, 2011
Last Update Posted : March 3, 2017
Information provided by (Responsible Party):
Mario Negri Institute for Pharmacological Research

Brief Summary:

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 or disease Intervention/treatment Phase
Type 2 Diabetes Drug: Paricalcitol Other: placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 112 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : September 2011
Actual Primary Completion Date : July 2015
Actual Study Completion Date : July 2015

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Paricalcitol Drug: Paricalcitol
1-month Paricalcitol 2mcg/day

Placebo Comparator: placebo Other: placebo
1-month Placebo Treatment

Primary Outcome Measures :
  1. Changes in urinary albumin excretion from baseline at 4 month. [ Time Frame: At baseline and 1,2,3 and 4 month. ]

Secondary Outcome Measures :
  1. Ambulatory and 24-hour blood pressure profile. [ Time Frame: At 1 month. ]
  2. Ambulatory and 24-hour blood pressure profile. [ Time Frame: At 2 month. ]
  3. Ambulatory and 24-hour blood pressure profile. [ Time Frame: At 3 month. ]
  4. Ambulatory and 24-hour blood pressure profile. [ Time Frame: At 4 month. ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01393808

ASL of Ponte San Pietro - Diabetologic Unit
Brembate, Bergamo, Italy, 24030
Clinical Research Center fo Rare Diseases Aldo and Cele Daccò
Ranica, Bergamo, Italy, 24020
Azienda Ospedaliera di Treviglio e Caravaggio - Unit of Diabetology and Metabolic Diseases
Romano di Lombardia, BG, Italy
Azienda Ospedaliera Bolognini - Unità di Medicina
Seriate, BG, Italy
Azienda Ospedaliera di Treviglio e Caravaggio - Unit of Diabetology and Metabolic Diseases
Treviglio, BG, Italy
Azienda Ospedaliera Ospedali Riuniti di Bergamo
Bergamo, Italy
Sponsors and Collaborators
Mario Negri Institute for Pharmacological Research

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Mario Negri Institute for Pharmacological Research Identifier: NCT01393808     History of Changes
Other Study ID Numbers: PROCEED
2011-001713-14 ( EudraCT Number )
First Posted: July 13, 2011    Key Record Dates
Last Update Posted: March 3, 2017
Last Verified: March 2017

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

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