title: 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.
abstract: BACKGROUND
  There are limited therapeutic options to slow the progression of autosomal dominant polycystic kidney disease (ADPKD). Recent clinical studies indicate that somatostatin analogues are promising for treating polycystic liver disease and potentially also for the kidney phenotype. We report on the design of the DIPAK 1 (Developing Interventions to Halt Progression of ADPKD 1) Study, which will examine the efficacy of the somatostatin analogue lanreotide on preservation of kidney function in ADPKD.
  
  
  METHODS
  The DIPAK 1 Study is an investigator-driven, randomized, multicenter, controlled, clinical trial.
  
  
  METHODS
  We plan to enroll 300 individuals with ADPKD and estimated glomerular filtration rate (eGFR) of 30-60 mL/min/1.73 m(2) who are aged 18-60 years.
  
  
  METHODS
  Patients will be randomly assigned (1:1) to standard care or lanreotide, 120 mg, subcutaneously every 28 days for 120 weeks, in addition to standard care.
  
  
  RESULTS
  Main study outcome is the slope through serial eGFR measurements starting at week 12 until end of treatment for lanreotide versus standard care. Secondary outcome parameters include change in eGFR from pretreatment versus 12 weeks after treatment cessation, change in kidney volume, change in liver volume, and change in quality of life.
  
  
  METHODS
  Blood and urine will be collected and questionnaires will be filled in following a fixed scheme. Magnetic resonance imaging will be performed for assessment of kidney and liver volume.
  
  
  RESULTS
  Assuming an average change in eGFR of 5.2 ± 4.3 (SD) mL/min/1.73 m(2) per year in untreated patients, 150 patients are needed in each group to detect a 30% reduction in the rate of kidney function loss between treatment groups with 80% power, 2-sided α = 0.05, and 20% protocol violators and/or dropouts.
  
  
  CONCLUSIONS
  The design is an open randomized controlled trial and measurement of our primary end point does not begin at randomization.
  
  
  CONCLUSIONS
  The DIPAK 1 Study will show whether subcutaneous administration of lanreotide every 4 weeks attenuates disease progression in patients with ADPKD.
authors.affiliation: Department of Nephrology, University Medical Center Groningen, University Hospital Groningen, Groningen, the Netherlands. Electronic address: esther.meijer@umcg.nl.
authors.forename: Esther
authors.initials: E
authors.lastname: Meijer
authors.affiliation: Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
authors.forename: Joost P H
authors.initials: JP
authors.lastname: Drenth
authors.affiliation: Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
authors.forename: Hedwig
authors.initials: H
authors.lastname: d'Agnolo
authors.affiliation: Department of Nephrology, University Medical Center Groningen, University Hospital Groningen, Groningen, the Netherlands.
authors.forename: Niek F
authors.initials: NF
authors.lastname: Casteleijn
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Johan W
authors.initials: JW
authors.lastname: de Fijter
authors.affiliation: Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
authors.forename: Tom J
authors.initials: TJ
authors.lastname: Gevers
authors.affiliation: Department of Radiology, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Kappert
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Dorien J M
authors.initials: DJ
authors.lastname: Peters
authors.affiliation: Department of Nephrology, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Salih
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Darius
authors.initials: D
authors.lastname: Soonawala
authors.affiliation: Department of Nephrology, University Medical Center Groningen, University Hospital Groningen, Groningen, the Netherlands.
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Spithoven
authors.affiliation: Department of Nephrology and Hypertension, Mayo Clinic, Rochester, MN.
authors.forename: Vicente E
authors.initials: VE
authors.lastname: Torres
authors.affiliation: Department of Nephrology, University Medical Center Groningen, University Hospital Groningen, Groningen, the Netherlands.
authors.forename: Folkert W
authors.initials: FW
authors.lastname: Visser
authors.affiliation: Department of Nephrology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
authors.forename: Jack F M
authors.initials: JF
authors.lastname: Wetzels
authors.affiliation: Department of Nephrology, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Robert
authors.initials: R
authors.lastname: Zietse
authors.affiliation: Department of Nephrology, University Medical Center Groningen, University Hospital Groningen, Groningen, the Netherlands.
authors.forename: Ron T
authors.initials: RT
authors.lastname: Gansevoort
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000627:therapeutic use*; D016891:Polycystic Kidney, Autosomal Dominant / Q000188:drug therapy* / Q000503:physiopathology; D011788:Quality of Life; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin
keywords: Polycystic kidney disease (PKD); cyst progression; disease trajectory; glomerular filtration rate (GFR); kidney volume; quality of life (QoL); renal disease; somatostatin analog