Pilot Study of Rapamycin as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD)

NCT00286156 | Completed Phase 1 Results DMC

• 1 other identifier: 7736
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a prospective, randomized, open-label, pilot clinical trial designed to compare the effects of an agent that has antiproliferative (1,2), antiangiogenesis (3),and tumor-progression blocking capabilities (4), namely, rapamycin (Rapamune®), in the treatment of autosomal-dominant polycystic kidney disease (ADPKD). Up to this time, only generic renal disease treatments for ADPKD have been in use, such as the treatment of hypertension, urinary tract infections, renal stones, renal call carcinomas, and replacement therapy with dialysis and/or renal transplantation. The fundamental aberrations in ADPKD are proliferation of cyst-forming tubuloepithelial cells, secretion of cytokine-rich fluid into those cysts, and progressive cyst expansion and release of inflammatory mediators that injure surrounding normal renal tissue. Consequently, therapy directed specifically at blocking the proliferation of tubuloepithelial cells and their tendency to malignant transformation, as well as impeding their blood supply, should have obvious merit. General Procedures: In Group I participants will have an iothalamate glomerular filtration rate (GFR) equal to or greater than 60 ml/min/1.73 m2, and in Group II participants will have a GFR less than 25-59 ml/min/1.73 m2. Both males and females with ADPKD who volunteer and qualify, will be randomly and prospectively assigned to treatment with rapamycin at either a high or low trough blood level or to standard care (each 1/3 of enrolled patients) for one year. The two treatment groups will receive rapamycin doses aimed at maintaining the 20- to 24-hour trough blood levels at either 2 to 5 ng/mL (low-dose), or greater than 5 to 8 ng/mL (high-dose). These trough levels are in the lower range of levels used when treating renal transplant recipients in whom trough levels are typically maintained between 5 and 15 ng/mL.

Conditions

Polycystic Kidney Diseases

Keywords

ADPKD

Outcome Measures

Primary Outcomes (1)

• Change in GFR From Baseline to 12 Months

  GFR (glomerular filtration rate) was measured by iothalamate. GFR is a key indicator of renal function.

  From baseline to 12 months

Secondary Outcomes (1)

• Change in Total Kidney Volume as Measured by 3D-CT From Baseline to 12 Months

  From baseline to 12 months

Study Arms (3)

1

EXPERIMENTAL

Arm 1 Rapamune dose 2-6mg aimed at maintaining trough levels 5-8 ng/ml

Drug: Rapamune

2

EXPERIMENTAL

Arm 2 Rapamune dose 2-6 mg aimed at maintaining trough levels of 2-5ng/ml

Drug: Rapamune

3

NO INTERVENTION

Standard Care

Interventions

Rapamune DRUG

Group 1- doses of Rapamune aimed at maintaining trough levels 5-8ng/ml Group 2 - doses of Rapamune aimed at maintaining trough levels 2-5ng/ml Group 3- Standard Care

Also known as: Rapamycin

1; 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ADPKD
• \> 18 y.o. GFR greater than or equal to 25. Willingness to be randomized to any treatment group Willingness to follow protocol requirements-frequent testing and follow-up required at Cleveland Clinic(Cleveland, OH) signed informed consent Willingness to use birth control(male and female)

You may not qualify if:

• Pregnancy
• post partum
• lactating
• system illness with renal involvement

Sponsors & Collaborators

• The Cleveland Clinic: lead
• Wyeth is now a wholly owned subsidiary of Pfizer: collaborator

Study Sites (1)

The Cleveland Clinic- main campus

Cleveland, Ohio, 44195, United States

Location

Related Publications (1)

• 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

MeSH Terms

Conditions

Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr William Braun Consultant Staff Nephrology, Cleveland Clinic
• Organization: Cleveland Clinic

braunw@ccf.org

216/444/6995

Study Officials

• William E. Braun, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2006
• First Posted: February 3, 2006
• Study Start: October 1, 2006
• Primary Completion: March 1, 2012
• Study Completion: December 1, 2014
• Last Updated: April 6, 2015
• Results First Posted: April 6, 2015

Record last verified: 2014-03

Locations

US (1)