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

Esther Meijer, Joost P H Drenth, Hedwig D'Agnolo, Niek F. Casteleijn, Johan W. De Fijter, Tom J. Gevers, Peter Kappert, Dorien J M Peters, Mahdi Salih, Darius Soonawala, Edwin M. Spithoven, Vicente Torres, Folkert W. Visser, Jack F M Wetzels, Robert Zietse, Ron T. Gansevoort

Research output: Contribution to journalArticle

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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. Study Design The DIPAK 1 Study is an investigator-driven, randomized, multicenter, controlled, clinical trial. Setting & Participants We plan to enroll 300 individuals with ADPKD and estimated glomerular filtration rate (eGFR) of 30-60 mL/min/1.73 m2 who are aged 18-60 years. Intervention 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. Outcomes 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. Measurements 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 m2 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. Limitations 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.

Original languageEnglish (US)
Pages (from-to)446-455
Number of pages10
JournalAmerican Journal of Kidney Diseases
Volume63
Issue number3
DOIs
StatePublished - Mar 2014

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Autosomal Dominant Polycystic Kidney
Disease Progression
Glomerular Filtration Rate
Randomized Controlled Trials
Kidney
Somatostatin
Withholding Treatment
Liver
Random Allocation
Therapeutics
Quality of Life
Research Personnel
Magnetic Resonance Imaging
Outcome Assessment (Health Care)
lanreotide
Urine
Phenotype

Keywords

  • cyst progression
  • disease trajectory
  • glomerular filtration rate (GFR)
  • kidney volume
  • Polycystic kidney disease (PKD)
  • quality of life (QoL)
  • renal disease
  • somatostatin analog

ASJC Scopus subject areas

  • Nephrology

Cite this

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. / Meijer, Esther; Drenth, Joost P H; D'Agnolo, Hedwig; Casteleijn, Niek F.; De Fijter, Johan W.; Gevers, Tom J.; Kappert, Peter; Peters, Dorien J M; Salih, Mahdi; Soonawala, Darius; Spithoven, Edwin M.; Torres, Vicente; Visser, Folkert W.; Wetzels, Jack F M; Zietse, Robert; Gansevoort, Ron T.

In: American Journal of Kidney Diseases, Vol. 63, No. 3, 03.2014, p. 446-455.

Research output: Contribution to journalArticle

Meijer, E, Drenth, JPH, D'Agnolo, H, Casteleijn, NF, De Fijter, JW, Gevers, TJ, Kappert, P, Peters, DJM, Salih, M, Soonawala, D, Spithoven, EM, Torres, V, Visser, FW, Wetzels, JFM, Zietse, R & Gansevoort, RT 2014, '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', American Journal of Kidney Diseases, vol. 63, no. 3, pp. 446-455. https://doi.org/10.1053/j.ajkd.2013.10.011
Meijer, Esther ; Drenth, Joost P H ; D'Agnolo, Hedwig ; Casteleijn, Niek F. ; De Fijter, Johan W. ; Gevers, Tom J. ; Kappert, Peter ; Peters, Dorien J M ; Salih, Mahdi ; Soonawala, Darius ; Spithoven, Edwin M. ; Torres, Vicente ; Visser, Folkert W. ; Wetzels, Jack F M ; Zietse, Robert ; Gansevoort, Ron T. / 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. In: American Journal of Kidney Diseases. 2014 ; Vol. 63, No. 3. pp. 446-455.
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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. Study Design The DIPAK 1 Study is an investigator-driven, randomized, multicenter, controlled, clinical trial. Setting & Participants We plan to enroll 300 individuals with ADPKD and estimated glomerular filtration rate (eGFR) of 30-60 mL/min/1.73 m2 who are aged 18-60 years. Intervention 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. Outcomes 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. Measurements 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 m2 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. Limitations 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.",
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AU - Drenth, Joost P H

AU - D'Agnolo, Hedwig

AU - Casteleijn, Niek F.

AU - De Fijter, Johan W.

AU - Gevers, Tom J.

AU - Kappert, Peter

AU - Peters, Dorien J M

AU - Salih, Mahdi

AU - Soonawala, Darius

AU - Spithoven, Edwin M.

AU - Torres, Vicente

AU - Visser, Folkert W.

AU - Wetzels, Jack F M

AU - Zietse, Robert

AU - Gansevoort, Ron T.

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N2 - 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. Study Design The DIPAK 1 Study is an investigator-driven, randomized, multicenter, controlled, clinical trial. Setting & Participants We plan to enroll 300 individuals with ADPKD and estimated glomerular filtration rate (eGFR) of 30-60 mL/min/1.73 m2 who are aged 18-60 years. Intervention 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. Outcomes 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. Measurements 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 m2 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. Limitations 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.

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KW - disease trajectory

KW - glomerular filtration rate (GFR)

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KW - Polycystic kidney disease (PKD)

KW - quality of life (QoL)

KW - renal disease

KW - somatostatin analog

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