Salt Intake and Antiproteinuric Effect of Paricalcitol in Type 2 Diabetes

Type 2 Diabetes Clinical Trial

— PROCEED  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01393808
• Other study ID #: PROCEED
• Secondary ID: 2011-001713-14
• Status: Completed
• Phase: Phase 2
• First received: July 12, 2011
• Last updated: March 2, 2017
• Start date: September 2011
• Est. completion date: July 2015

Study information

• Verified date: March 2017
• Source: Mario Negri Institute for Pharmacological Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 112
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Paricalcitol
1-month Paricalcitol 2mcg/day

Other:
• placebo
1-month Placebo Treatment

Locations

Country	Name	City	State
Italy	Azienda Ospedaliera Ospedali Riuniti di Bergamo	Bergamo
Italy	ASL of Ponte San Pietro - Diabetologic Unit	Brembate	Bergamo
Italy	Clinical Research Center fo Rare Diseases Aldo and Cele Daccò	Ranica	Bergamo
Italy	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

Sponsors (2)

Lead Sponsor	Collaborator
Mario Negri Institute for Pharmacological Research	Abbott

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in urinary albumin excretion from baseline at 4 month.		At baseline and 1,2,3 and 4 month.
Secondary	Ambulatory and 24-hour blood pressure profile.		At 1 month.
Secondary	Ambulatory and 24-hour blood pressure profile.		At 2 month.
Secondary	Ambulatory and 24-hour blood pressure profile.		At 3 month.
Secondary	Ambulatory and 24-hour blood pressure profile.		At 4 month.