Clinical trial NCT01393808: Salt Intake and Antiproteinuric Effect of Paricalcitol in Type 2 Diabetes
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes
Keywords: Type 2 diabetes
Paricalcitol
Proteinuria
Sodium intake
Lead sponsor: Mario Negri Institute for Pharmacological Research
Sponsor class: OTHER
Collaborators: name: Abbott
First posted: 2011-07-13
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Changes in urinary albumin excretion from baseline at 4 month.
timeFrame: At baseline and 1,2,3 and 4 month.
Secondary outcomes:
measure: Ambulatory and 24-hour blood pressure profile.
timeFrame: At 1 month.
measure: Ambulatory and 24-hour blood pressure profile.
timeFrame: At 2 month.
measure: Ambulatory and 24-hour blood pressure profile.
timeFrame: At 3 month.
measure: Ambulatory and 24-hour blood pressure profile.
timeFrame: At 4 month.
Other outcomes:
Locations:
city: Brembate
country: Italy
facility: ASL of Ponte San Pietro - Diabetologic Unit
state: Bergamo
city: Ranica
country: Italy
facility: Clinical Research Center fo Rare Diseases Aldo and Cele Daccò
state: Bergamo
city: Romano di Lombardia
country: Italy
facility: Azienda Ospedaliera di Treviglio e Caravaggio - Unit of Diabetology and Metabolic Diseases
state: BG
city: Seriate
country: Italy
facility: Azienda Ospedaliera Bolognini - Unità di Medicina
state: BG
city: Treviglio
country: Italy
facility: Azienda Ospedaliera di Treviglio e Caravaggio - Unit of Diabetology and Metabolic Diseases
state: BG
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti di Bergamo
Study officials:
References:
citation: Prabhu RA, Saraf K. Vitamin D in diabetic nephropathy. J Postgrad Med. 2018 Jan-Mar;64(1):5-6. doi: 10.4103/jpgm.JPGM_311_17. No abstract available.
citation: Parvanova A, Trillini M, Podesta MA, Iliev IP, Ruggiero B, Abbate M, Perna A, Peraro F, Diadei O, Rubis N, Gaspari F, Carrara F, Stucchi N, Belviso A, Bossi AC, Trevisan R, Remuzzi G, de Borst M, Ruggenenti P; PROCEED Study Organization and the Scientific Writing Academy (SWA) 2016. Moderate salt restriction with or without paricalcitol in type 2 diabetes and losartan-resistant macroalbuminuria (PROCEED): a randomised, double-blind, placebo-controlled, crossover trial. Lancet Diabetes Endocrinol. 2018 Jan;6(1):27-40. doi: 10.1016/S2213-8587(17)30359-5. Epub 2017 Nov 2.