Sirolimus In Autosomal Dominant Polycystic Kidney Disease And Severe Renal Insufficiency

NCT01223755 | Terminated Phase 2

• 2 other identifiers: SIRENA-II2007-005047-21
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

The general aim of this study in adult patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) and severe renal insufficiency is to assess the safety and the efficacy of sirolimus (SRL) in slowing renal function decline as compared to conventional therapy.

Conditions

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Keywords

Autosomal dominant polycystic kidney disease; Sirolimus; Renal insufficiency

Outcome Measures

Primary Outcomes (4)

• Glomerular Filtration Rate (GFR)

  To compare changes over baseline of GFR (delta GFR) measured by plasma iohexol clearance in SRL and conventional treatment ADPKD patients.

  At baseline.

• Glomerular Filtration Rate (GFR)

  To compare changes over baseline of GFR (delta GFR) measured by plasma iohexol clearance in SRL and conventional treatment ADPKD patients.

  At 12th month .

• Glomerular Filtration Rate (GFR)

  To compare changes over baseline of GFR (delta GFR) measured by plasma iohexol clearance in SRL and conventional treatment ADPKD patients.

  After six months from baseline.

• Glomerular Filtration Rate (GFR)

  To compare changes over baseline of GFR (delta GFR) measured by plasma iohexol clearance in SRL and conventional treatment ADPKD patients.

  Every 12 months.

Secondary Outcomes (6)

• Liver volume parameters.

  At baseline.

• Renal volume parameters.

  At baseline.

• Liver volume parameters.

  At 12 month.

• Liver volume parameters.

  At 36 month.

• Renal volume parameters.

  At 12 month.

Study Arms (2)

Sirolimus

EXPERIMENTAL

Drug: Sirolimus

conventional therapy

ACTIVE COMPARATOR

Drug: conventional therapy

Interventions

Sirolimus DRUG

Patients will be given SRL for one year starting at the oral daily dose of 3 mg, with periodical whole blood level measurements. The daily dose will be adjusted to keep SRL concentration within 5-10 ng/ml. Drug levels will be assessed at day 7 after starting treatment and every two weeks for the first month. Subsequently SRL concentrations will be monitored at monthly intervals (or at least 5 days after drug dose adjustments) until the end of the treatment period.

Also known as: Rapamune

Sirolimus

conventional therapy DRUG

Conventional treatment relates usually to the administration of antihypertensive drugs for patients with high blood pressure. Thus, for the present study, no major change in antihypertensive treatment should be introduced throughout the whole study period unless deemed clinically necessary (the reasons of the changes should be, however, clearly explained in the CRF). Only small changes in the doses of the ongoing treatments are recommended in order to maintain the same level of blood pressure control (target systolic/diastolic blood pressure \<130/80 mmHg). This approach is aimed to minimize the confounding effect of any change in concomitant treatments on some efficacy variables (such as urinary protein excretion rate).

conventional therapy

Eligibility Criteria

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

You may qualify if:

• Age \> 18 years
• Clinical and ultrasound diagnosis of ADPKD
• GFR 40-15 ml/min/1.73 m2 (estimated by the 4 variable MDRD equation)
• Urinary protein excretion rate \< 0.5 g/ 24 hrs
• Written informed consent

You may not qualify if:

• Diabetes
• Urinary protein excretion rate \>0.5 g/ 24 hrs or abnormal urinalysis suggestive of concomitant, clinically significant glomerular disease
• Urinary tract lithiasis, infection or obstruction
• Cancer
• Psychiatric disorders and any condition that might prevent full comprehension of the purposes and risks of the study
• Pregnancy, lactation or child bearing potential and ineffective contraception (estrogen therapy in post menopausal women should not be stopped)

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead

Study Sites (1)

Mario Negri Institute - Clinical Research Center for Rare Diseases

Ranica, Bergamo, 24020, Italy

Location

Related Publications (2)

• St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.

  PMID: 39356039 DERIVED

• Ruggenenti P, Gentile G, Perico N, Perna A, Barcella L, Trillini M, Cortinovis M, Ferrer Siles CP, Reyes Loaeza JA, Aparicio MC, Fasolini G, Gaspari F, Martinetti D, Carrara F, Rubis N, Prandini S, Caroli A, Sharma K, Antiga L, Remuzzi A, Remuzzi G; SIRENA 2 Study Group. Effect of Sirolimus on Disease Progression in Patients with Autosomal Dominant Polycystic Kidney Disease and CKD Stages 3b-4. Clin J Am Soc Nephrol. 2016 May 6;11(5):785-794. doi: 10.2215/CJN.09900915. Epub 2016 Feb 22.

  PMID: 26912555 DERIVED

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant; Renal Insufficiency

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Polycystic Kidney Diseases; Kidney Diseases, Cystic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ciliopathies; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2010
• First Posted: October 19, 2010
• Study Start: September 1, 2010
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: February 25, 2013

Record last verified: 2013-02

Locations

IT (1)