Study of Lanreotide to Treat Polycystic Kidney Disease

NCT01616927 | Unknown Phase 3 DMC

• 2 other identifiers: DIPAK12011-005017-37
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 4

Brief Summary

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst formation in both kidneys, in most patients leading to end stage renal disease. It is the most common hereditary renal disease with a prevalence of approximately 1 in 1,000 persons. The majority of patients also have progressive cyst formation in the liver, leading to pain, gastrointestinal discomfort and sometimes the need for liver transplantation. At present there is no proven therapeutic intervention to slow the rate of disease progression in human ADPKD. The development of renoprotective treatments that are well tolerated, is therefore of major importance. In this respect, somatostatin analogues are promising for especially polycystic liver disease, but also for the renal phenotype. However, the studies that have been performed thus far with these agents, were underpowered and of too short duration to reach a definitive conclusion on the potential reno- and hepatoprotective efficacy of somatostatin analogues. Therefore, the present study is designed as a randomised clinical trial with sufficient duration of follow-up to investigate whether the somatostatin analogue Lanreotide slows progression of polycystic kidney and liver disease in ADPKD-patients. To this end, 300 ADPKD patients, aged 18-60years, with an eGFR 30-60 ml/min/1.73 m2) will be randomized 1:1 to standard care or monthly subcutaneous lanreotide injections on top off standard care. These 300 subjects will go through 15 study visits in 3 years and 1 follow up visit. During these visits, questionnaires will be filled in, physical examinations will be performed, blood will be drawn and urine collected. After study completion, rate of renal function decline in lanreotide treated subjects will be compared to that of subject who received standard care.

Conditions

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Keywords

ADPKD; lanreotide; polycystic kidney; polycystic liver

Outcome Measures

Primary Outcomes (1)

• Change in renal function

  Change in renal function in Lanreotide versus not treated patients, as assessed as slope through all eGFR measurements taken at study visits during the treatment phase of the trial (n=10), with the value obtained at month 3 as first eGFR value for slope analysis.

  serial eGFR measurements from month 3 until end of treatment visit (month 30)

Secondary Outcomes (6)

• change in renal volume

  baseline and 3 months after end of treatment (follow-up; month 33)

• change in liver volume

  Baseline and end of treatment (month 30)

• change in quality of life

  baseline-end of treatment (month 30)

• tolerance

  baseline-end of treatment(month 30)

• change in renal function

  baseline and 3 months after end of treatment (follow-up; month 33)

Study Arms (2)

standard care

NO INTERVENTION

Subjects in this arm will receive standard care

Lanreotide

EXPERIMENTAL

Drug: Lanreotide

Interventions

Lanreotide DRUG

Lanreotide will be administered once every 4 weeks as a subcutaneous injection

Also known as: somatuline, lanreotide autogel

Lanreotide

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of ADPKD, based upon the modified Ravine criteria
• Age between 18 and 60 years.
• eGFR (MDRD) between 30 and 60 ml/min/1.73 m2.
• Providing informed consent.

You may not qualify if:

• Patients who, in the opinion of the study investigator may present a safety risk.
• Patients who are unlikely to adequately comply with the trial's procedures \[due for instance to medical conditions likely to require an extended interruption or discontinuation, history of substance abuse or noncompliance).
• a. Patients taking medications or having concomitant illnesses likely to confound endpoint assessments (e.g. nephrotoxic medications such as chronic NSAID, cyclosporine, lithium immunosuppressant use) b. Patients having concomitant illnesses likely to confound endpoint assessments (e.g. diabetes mellitus for which medication is needed and patients with proteinuria \> 1 g /24hr).
• Patients who underwent surgical or drainage interventions for cystic kidney disease the year before study-entry or are likely candidates for these procedures within 2 years of start of the study.
• Patients taking other experimental (i.e.,non approved by FDA/EMA or indication of ADPKD) therapies.
• Patients having used Lanreotide (or another somatostatin analogue) in the 3 months before study start.
• Patients with known intolerance for Lanreotide (or another somatostatin analogue).
• Unwillingness to comply with reproductive precautions. Women who are capable of becoming pregnant must be willing to comply with approved birth control from two-weeks prior to, and for 60 days after taking investigational product.
• Women, who are pregnant or breastfeeding.
• Patients, who suffer from cardiac arrhythmias, that are thought to be dangerous in combination with lanreotide administration.
• Patients, who ever suffered from symptomatic gallstones and did not undergo cholecystectomy.
• Patients, who have a medical history of pancreatitis.
• Patients, who have a medical history of infected liver cysts.
• In addition:
• Patients, who underwent liver cyst drainage or surgery in the year before, can enter the study, but will not be assessed for change in liver volume.

Sponsors & Collaborators

• University Medical Center Groningen: lead
• Leiden University Medical Center: collaborator
• Erasmus Medical Center: collaborator
• Radboud University Medical Center: collaborator

Study Sites (4)

University Medical Center Groningen

Groningen, Netherlands

Location

Leiden University Medical Center

Leiden, Netherlands

Location

Radboud University Medical Center

Nijmegen, Netherlands

Location

Erasmus Medisch Centrum

Rotterdam, Netherlands

Location

Related Publications (6)

• Meijer E, Drenth JP, d'Agnolo H, Casteleijn NF, de Fijter JW, Gevers TJ, Kappert P, Peters DJ, Salih M, Soonawala D, Spithoven EM, Torres VE, Visser FW, Wetzels JF, Zietse R, Gansevoort RT; DIPAK Consortium. Rationale and design of the DIPAK 1 study: a randomized controlled clinical trial assessing the efficacy of lanreotide to Halt disease progression in autosomal dominant polycystic kidney disease. Am J Kidney Dis. 2014 Mar;63(3):446-55. doi: 10.1053/j.ajkd.2013.10.011. Epub 2013 Dec 15.

  PMID: 24342522 BACKGROUND

• Lantinga MA, D'Agnolo HM, Casteleijn NF, de Fijter JW, Meijer E, Messchendorp AL, Peters DJ, Salih M, Spithoven EM, Soonawala D, Visser FW, Wetzels JF, Zietse R, Drenth JP, Gansevoort RT; DIPAK Consortium. Hepatic Cyst Infection During Use of the Somatostatin Analog Lanreotide in Autosomal Dominant Polycystic Kidney Disease: An Interim Analysis of the Randomized Open-Label Multicenter DIPAK-1 Study. Drug Saf. 2017 Feb;40(2):153-167. doi: 10.1007/s40264-016-0486-x.

  PMID: 27995519 RESULT

• 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

• Aapkes SE, de Haas RJ, Bernts LHP, Blijdorp CJ, Dekker SEI, van Gastel MDA, Meijer E, Veldman A, Drenth JPH, Gansevoort RT; DIPAK consortium. Incident Gallstones During Somatostatin Analog Treatment are Associated with Acute Biliary Complications Especially After Discontinuation. Drugs R D. 2021 Jun;21(2):179-188. doi: 10.1007/s40268-021-00342-7. Epub 2021 Mar 29.

  PMID: 33779943 DERIVED

• van Aerts RMM, Kievit W, D'Agnolo HMA, Blijdorp CJ, Casteleijn NF, Dekker SEI, de Fijter JW, van Gastel M, Gevers TJ, van de Laarschot LFM, Lantinga MA, Losekoot M, Meijer E, Messchendorp AL, Neijenhuis MK, Pena MJ, Peters DJM, Salih M, Soonawala D, Spithoven EM, Visser FW, Wetzels JF, Zietse R, Gansevoort RT, Drenth JPH; DIPAK-1 Investigators. Lanreotide Reduces Liver Growth In Patients With Autosomal Dominant Polycystic Liver and Kidney Disease. Gastroenterology. 2019 Aug;157(2):481-491.e7. doi: 10.1053/j.gastro.2019.04.018. Epub 2019 Apr 22.

  PMID: 31022403 DERIVED

• Meijer E, Visser FW, van Aerts RMM, Blijdorp CJ, Casteleijn NF, D'Agnolo HMA, Dekker SEI, Drenth JPH, de Fijter JW, van Gastel MDA, Gevers TJ, Lantinga MA, Losekoot M, Messchendorp AL, Neijenhuis MK, Pena MJ, Peters DJM, Salih M, Soonawala D, Spithoven EM, Wetzels JF, Zietse R, Gansevoort RT; DIPAK-1 Investigators. Effect of Lanreotide on Kidney Function in Patients With Autosomal Dominant Polycystic Kidney Disease: The DIPAK 1 Randomized Clinical Trial. JAMA. 2018 Nov 20;320(19):2010-2019. doi: 10.1001/jama.2018.15870.

  PMID: 30422235 DERIVED

Related Links

• General description of the DIPAK consortium, including the DIPAK intervention study

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant; Polycystic Kidney Diseases; Polycystic liver disease

Interventions

lanreotide

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

Study Officials

• Ron Gansevoort, MD, PhD

  University Medical Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor in Nephrology

Study Record Dates

• First Submitted: June 6, 2012
• First Posted: June 12, 2012
• Study Start: June 1, 2012
• Primary Completion: August 1, 2017
• Study Completion: December 1, 2017
• Last Updated: May 23, 2017

Record last verified: 2017-05

Locations

NL (4)