Study of Lanreotide to Treat Polycystic Kidney Disease
Information source: University Medical Center Groningen
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Intervention: Lanreotide (Drug)
Phase: Phase 3
Status: Active, not recruiting
Sponsored by: University Medical Center Groningen Official(s) and/or principal investigator(s): Ron Gansevoort, MD, PhD, Principal Investigator, Affiliation: University Medical Centre
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.
Clinical Details
Official title: The DIPAK 1 Study: A Randomised, Controlled Clinical Trial Assessing the Efficacy of Lanreotide to Halt Disease Progression in ADPKD
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Change in renal function
Secondary outcome: change in renal volumechange in liver volume change in quality of life tolerance change in renal function Incidence of worsening renal function
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
Eligibility
Minimum age: 18 Years.
Maximum age: 60 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Diagnosis of ADPKD, based upon the modified Ravine criteria
2. Age between 18 and 60 years.
3. eGFR (MDRD) between 30 and 60 ml/min/1. 73 m2.
4. Providing informed consent.
Exclusion Criteria:
1. Patients who, in the opinion of the study investigator may present a safety risk.
2. 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).
3. 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).
4. 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.
5. Patients taking other experimental (i. e.,non approved by FDA/EMA or indication of
ADPKD) therapies.
6. Patients having used Lanreotide (or another somatostatin analogue) in the 3 months
before study start.
7. Patients with known intolerance for Lanreotide (or another somatostatin analogue).
8. 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.
9. Women, who are pregnant or breastfeeding.
10. Patients, who suffer from cardiac arrhythmias, that are thought to be dangerous in
combination with lanreotide administration.
11. Patients, who ever suffered from symptomatic gallstones and did not undergo
cholecystectomy.
12. Patients, who have a medical history of pancreatitis.
13. 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.
Locations and Contacts
University Medical Center Groningen, Groningen, Netherlands
Leiden University Medical Center, Leiden, Netherlands
Radboud University Medical Center, Nijmegen, Netherlands
Erasmus Medisch Centrum, Rotterdam, Netherlands
Additional Information
General description of the DIPAK consortium, including the DIPAK intervention study This protocol has been reviewed and accepted by the Lancet
Related publications: 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.
Starting date: June 2012
Last updated: May 27, 2015
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