Study of Lanreotide to Treat Polycystic Kidney Disease (DIPAK1)
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.
|Autosomal Dominant Polycystic Kidney Disease (ADPKD)||Drug: Lanreotide||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||The DIPAK 1 Study: A Randomised, Controlled Clinical Trial Assessing the Efficacy of Lanreotide to Halt Disease Progression in ADPKD|
- Change in renal function [ Time Frame: serial eGFR measurements from month 3 until end of treatment visit (month 30) ]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.
- change in renal volume [ Time Frame: baseline and 3 months after end of treatment (follow-up; month 33) ]to determine whether Lanreotide modifies ADPKD progression as measured by change in renal volume in the overall study population. Renal volume is measured at baseline, after 30 months of treatment and 3 months afterwards (follow-up visit).
- change in liver volume [ Time Frame: Baseline and end of treatment (month 30) ]to determine whether Lanreotide modifies ADPKD progression as measured by change in liver volume in the subset of ADPKD patients with moderate to severe polycystic liver disease, defined as a liver volume of >2000 ml. Liver volume is measured at baseline, at month 30 and 3 months afterwards (follow-up visit))
- change in quality of life [ Time Frame: baseline-end of treatment (month 30) ]to determine whether Lanreotide changes the quality of life (using specific questionnaires). These questionnaires will be filled in at baseline, after 3 months of treatment, after 1 year, after 2 years, at end of treatment (30 months) and at follow-up (3 months after end of treatment)
- tolerance [ Time Frame: baseline-end of treatment(month 30) ]to determine whether lanreotide is safe and well tolerated. This is assessed by investigating (severe)adverse events, vital signs, performing physical examination and clinical laboratory tests.
- change in renal function [ Time Frame: baseline and 3 months after end of treatment (follow-up; month 33) ]change in renal function in Lanreotide versus not treated patients, as assessed as change in eGFR from baseline versus eGFR obtained 3 months after cessation of treatment.
- Incidence of worsening renal function [ Time Frame: from baseline ]incidence of worsening renal function defined as a 30% decrease in eGFR and/or need for renal replacement therapy computed from pre-treatment eGFR
|Study Start Date:||June 2012|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||August 2017 (Final data collection date for primary outcome measure)|
No Intervention: standard care
Subjects in this arm will receive standard care
Lanreotide will be administered once every 4 weeks as a subcutaneous injection
First, to determine whether Lanreotide attenuates progression of the renal phenotype in ADPKD patients as measured by change in rate of renal function decline and change in renal volume growth.
Second, to determine whether Lanreotide modifies progression of the liver phenotype in the subset of ADPKD patients with moderate to severe polycystic liver disease as measured by change in liver volume.
Investigator driven, randomized, multi-center, controlled clinical trial.
300 subjects, diagnosed with ADPKD, based on the revised Ravine criteria, with advanced disease and high likelihood of rapid disease progression (eGFR between 30 and 60 ml/min/1.73 m2 and age between 18 and 60 years).
Patients will be randomized (1:1) into two groups. One group will receive a dose of Lanreotide 120 mg sc every 28 days for 30 months. The dose of Lanreotide will be eGFR (BSA unadjusted) dependent. Subjects that reach an eGFR <30ml/min during the study will receive Lanreotide 90 mg sc every 28 days. Down-titration will also occur in case of dose related side effects. The other group of patients will receive standard care.
Main study endpoint:
Change in renal function in Lanreotide versus not treated patients, as assessed as slope through serial eGFR measurements over time during the treatment phase of the trial, with the value obtained at month 3 as first eGFR value for slope analysis.
Main secondary outcome variables:
- to determine whether Lanreotide modifies ADPKD progression as measured by change in renal volume in the overall study population,
- to determine whether Lanreotide modifies ADPKD progression as measured by change in liver volume in the subset of ADPKD patients with moderate to severe polycystic liver disease
- to determine whether Lanreotide changes the quality of life
- to determine whether Lanreotide is well tolerated
Please refer to this study by its ClinicalTrials.gov identifier: NCT01616927
|University Medical Center Groningen|
|Leiden University Medical Center|
|Radboud University Medical Center|
|Erasmus Medisch Centrum|
|Principal Investigator:||Ron Gansevoort, MD, PhD||University Medical Centre|