Salt Intake and Antiproteinuric Effect of Paricalcitol in Type 2 Diabetes

NCT01393808 | Completed Phase 2

• 2 other identifiers: PROCEED2011-001713-14
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 6

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.

Conditions

Type 2 Diabetes

Keywords

Type 2 diabetes; Paricalcitol; Proteinuria; Sodium intake

Outcome Measures

Primary Outcomes (1)

• Changes in urinary albumin excretion from baseline at 4 month.

  At baseline and 1,2,3 and 4 month.

Secondary Outcomes (4)

• Ambulatory and 24-hour blood pressure profile.

  At 1 month.

• Ambulatory and 24-hour blood pressure profile.

  At 2 month.

• Ambulatory and 24-hour blood pressure profile.

  At 3 month.

• Ambulatory and 24-hour blood pressure profile.

  At 4 month.

Study Arms (2)

Paricalcitol

EXPERIMENTAL

Drug: Paricalcitol

placebo

PLACEBO COMPARATOR

Other: placebo

Interventions

Paricalcitol DRUG

1-month Paricalcitol 2mcg/day

Paricalcitol

placebo OTHER

1-month Placebo Treatment

placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead
• Abbott: collaborator

Study Sites (6)

Azienda Ospedaliera Ospedali Riuniti di Bergamo

Bergamo, Bergamo, Italy

Location

ASL of Ponte San Pietro - Diabetologic Unit

Brembate, Bergamo, 24030, Italy

Location

Clinical Research Center fo Rare Diseases Aldo and Cele Daccò

Ranica, Bergamo, 24020, Italy

Location

Azienda Ospedaliera di Treviglio e Caravaggio - Unit of Diabetology and Metabolic Diseases

Romano di Lombardia, BG, Italy

Location

Azienda Ospedaliera Bolognini - Unità di Medicina

Seriate, BG, Italy

Location

Azienda Ospedaliera di Treviglio e Caravaggio - Unit of Diabetology and Metabolic Diseases

Treviglio, BG, Italy

Location

Related Publications (3)

• Hodson EM, Cooper TE. Altered dietary salt intake for preventing diabetic kidney disease and its progression. Cochrane Database Syst Rev. 2023 Jan 16;1(1):CD006763. doi: 10.1002/14651858.CD006763.pub3.

  PMID: 36645291 DERIVED

• 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.

  PMID: 29386411 DERIVED

• 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.

  PMID: 29104158 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Proteinuria

Interventions

paricalcitol

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2011
• First Posted: July 13, 2011
• Study Start: September 1, 2011
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: March 3, 2017

Record last verified: 2017-03

Locations

IT (6)