DIPAK1: Study of Lanreotide to Treat Polycystic Kidney Disease

Sponsor

University Medical Center Groningen (Other)

Overall Status

Unknown status

CT.gov ID

NCT01616927

Collaborator

Leiden University Medical Center (Other), Erasmus Medical Center (Other), Radboud University Medical Center (Other)

300

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

1.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Autosomal Dominant Polycystic Kidney Disease (ADPKD)	Drug: Lanreotide	Phase 3

Detailed Description

Aims:

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.

Methods:

Investigator driven, randomized, multi-center, controlled clinical trial.

Study population:

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).

Intervention:

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

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

Study Start Date :

Jun 1, 2012

Anticipated Primary Completion Date :

Aug 1, 2017

Anticipated Study Completion Date :

Dec 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: standard care Subjects in this arm will receive standard care
Experimental: Lanreotide	Drug: Lanreotide Lanreotide will be administered once every 4 weeks as a subcutaneous injection Other Names: somatuline lanreotide autogel

Arm

Intervention/Treatment

No Intervention: standard care

Subjects in this arm will receive standard care

Experimental: Lanreotide

Drug: Lanreotide

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

Other Names:

somatuline

lanreotide autogel

Outcome Measures

Primary Outcome Measures

Change in renal function [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.

Secondary Outcome Measures

change in renal volume [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 [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 [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 [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 [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 [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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).
1. 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.
Patients having contraindications to, or interference with MRI assessments, as dictated by local regulation, will not be allowed to undergo MR imaging. However, these patients can enter the study, but will not be assessed for change in kidney and/or liver volume.

Contacts and Locations

Locations

	Site	City	Country
1	University Medical Center Groningen	Groningen	Netherlands
2	Leiden University Medical Center	Leiden	Netherlands
3	Radboud University Medical Center	Nijmegen	Netherlands
4	Erasmus Medisch Centrum	Rotterdam	Netherlands