Study of Lanreotide to Treat Polycystic Kidney Disease (DIPAK1)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University Medical Centre Groningen
Sponsor:
Collaborators:
Leiden University Medical Center
Erasmus Medical Center
Radboud University
Information provided by (Responsible Party):
dr. R.T. Gansevoort, University Medical Centre Groningen
ClinicalTrials.gov Identifier:
NCT01616927
First received: June 6, 2012
Last updated: January 20, 2014
Last verified: January 2014
  Purpose

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 Intervention Phase
Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Drug: Lanreotide
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University Medical Centre Groningen:

Primary Outcome Measures:
  • Change in renal function [ Time Frame: serial eGFR measurements from month 3 until end of treatment visit (month 30) ] [ Designated as safety issue: No ]
    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 [ Time Frame: baseline and 3 months after end of treatment (follow-up; month 33) ] [ Designated as safety issue: No ]
    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 3 months after end of treatment (follow-up; month 33) ] [ Designated as safety issue: No ]
    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)- follow-up (month 33) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: No ]
    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 3 months after randomization ] [ Designated as safety issue: No ]
    incidence of worsening renal function defined as a 30% decrease in eGFR and/or need for renal replacement therapy computed from 12 weeks post randomization


Estimated Enrollment: 300
Study Start Date: June 2012
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01616927

Contacts
Contact: Esther Meijer, MD, PhD esther.meijer@umcg.nl
Contact: Ron Gansevoort, MD, PhD r.t.gansevoort@umcg.nl

Locations
Netherlands
University Medical Center Groningen Recruiting
Groningen, Netherlands
Contact: Edwin Spithoven, MD    050-3610772    e.m.spithoven@umcg.nl   
Contact: Esther Meijer, MD, PhD    050-3612688    esther.meijer@umcg.nl   
Principal Investigator: Ron Gansevoort, MD, PhD         
Sub-Investigator: Edwin Spithoven, MD         
Leiden University Medical Center Not yet recruiting
Leiden, Netherlands
Contact: Darius Soonawala, MD    071-5262148    d.soonawala@lumc.nl   
Principal Investigator: Hans de Fijter, MD, PhD         
Sub-Investigator: Darius Soonawala, MD         
Radboud University Medical Center Not yet recruiting
Nijmegen, Netherlands
Contact: Tom Gevers, MD    024-3614760    t.gevers@mdl.umcn.nl   
Principal Investigator: Joost Drenth, MD, PhD         
Sub-Investigator: Tom Gevers, MD         
Erasmus Medisch Centrum Not yet recruiting
Rotterdam, Netherlands
Contact: Mahdi Salih, MD    010-7033050    m.salih@erasmusmc.nl   
Principal Investigator: Bob Zietse, MD, PhD         
Sub-Investigator: Mahdi Salih, MD         
Sponsors and Collaborators
University Medical Centre Groningen
Leiden University Medical Center
Erasmus Medical Center
Radboud University
Investigators
Principal Investigator: Ron Gansevoort, MD, PhD University Medical Centre
  More Information

Additional Information:
Publications:
Responsible Party: dr. R.T. Gansevoort, Associate Professor in Nephrology, University Medical Centre Groningen
ClinicalTrials.gov Identifier: NCT01616927     History of Changes
Other Study ID Numbers: DIPAK1, 2011-005017-37
Study First Received: June 6, 2012
Last Updated: January 20, 2014
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by University Medical Centre Groningen:
ADPKD
lanreotide
polycystic kidney
polycystic liver

Additional relevant MeSH terms:
Kidney Diseases
Polycystic Kidney Diseases
Multicystic Dysplastic Kidney
Polycystic Kidney, Autosomal Dominant
Urologic Diseases
Kidney Diseases, Cystic
Urogenital Abnormalities
Congenital Abnormalities
Lanreotide
Angiopeptin
Somatostatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Cardiovascular Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 19, 2014