Somatostatin in Polycystic Kidney: a Long-term Three Year Follow up Study (ALADIN)
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ClinicalTrials.gov Identifier: NCT00309283 |
Recruitment Status :
Completed
First Posted : March 31, 2006
Last Update Posted : April 24, 2013
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Tracking Information | ||||
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First Submitted Date ICMJE | March 30, 2006 | |||
First Posted Date ICMJE | March 31, 2006 | |||
Last Update Posted Date | April 24, 2013 | |||
Study Start Date ICMJE | April 2006 | |||
Actual Primary Completion Date | January 2012 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
Change over baseline of the total kidney volume at 1 and 3 years follow-up (estimated by gadolinium contrast enhanced and T2-weighted magnetic resonance imaging, MRI). [ Time Frame: Basal, 1 and 3 years follow-up ] | |||
Original Primary Outcome Measures ICMJE |
Change over baseline of the total kidney volume at 1 and 3 years follow-up (estimated by gadolinium contrast enhanced and T2-weighted magnetic resonance imaging, MRI). | |||
Change History | ||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | |||
Original Other Pre-specified Outcome Measures | Not Provided | |||
Descriptive Information | ||||
Brief Title ICMJE | Somatostatin in Polycystic Kidney: a Long-term Three Year Follow up Study | |||
Official Title ICMJE | Effect of a Long-acting Somatostatin on Disease Progression in Nephropathy Due to Autosomal Dominant Polycystic Kidney Disease: a Long-term Three Year Follow up Study | |||
Brief Summary | Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common hereditary renal disease, responsible for 8% to 10% of the cases of end stage renal disease (ESRD) in Western countries. At comparable levels of blood pressure control and proteinuria, patients with ADPKD have faster decline in glomerular filtration rate than those with other renal diseases and do not seem to benefit to the same extent of ACE inhibitor therapy. A reasonable explanation for the above findings is that in ADPKD progression is largely dependent on the development and growth of cysts and secondary disruption of normal tissue. Thus, renoprotective interventions in ADPKD - in addition to achieve maximal reduction of arterial blood pressure and proteinuria and to limit the effects of additional potential promoters of disease progression such as dyslipidemia, chronic hyperglycemia or smoking - should also be specifically aimed to correct the dysregulation of epithelial cell growth, secretion, and matrix interactions characteristic of the disease. Evidence that specific receptors for somatostatin are present in the kidney tissue, arises the possibility that somatostatin treatment in patients with ADPKD might inhibit fluid formation and eventually induce the shrinking of renal cysts.To evaluate the tolerability and the safety of long-acting somatostatin in ADPKD patients, a prospective cross-over controlled study has been recently performed. This pilot study demonstrated the safety of six month treatment of long-acting somatostatin in patients with ADPKD. Moreover, the percent increase of total kidney volume was significantly lower in patients on somatostatin than in placebo. Overall, these findings provide the basis for designing a long-term study in ADPKD patients aimed to document the efficacy of the somatostatin treatment in preventing further increase or even reducing the total kidney volume and the renal volume taken up by small cysts, eventually halting kidney disease progression. |
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Detailed Description | Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common hereditary renal disease, responsible for 8% to 10% of the cases of end stage renal disease (ESRD) in Western countries. At comparable levels of blood pressure control and proteinuria, patients with ADPKD have faster decline in glomerular filtration rate (GFR) than those with other renal diseases and do not seem to benefit to the same extent of ACE inhibitor therapy. A reasonable explanation for the above findings is that in ADPKD progression is largely dependent on the development and growth of cysts and secondary disruption of normal tissue. Thus, renoprotective interventions in ADPKD - in addition to achieve maximal reduction of arterial blood pressure and proteinuria and to limit the effects of additional potential promoters of disease progression such as dyslipidemia, chronic hyperglycemia or smoking - should also be specifically aimed to correct the dysregulation of epithelial cell growth, secretion, and matrix interactions characteristic of the disease. The fluid filling renal cysts in human polycystic kidney is formed mainly by a secretion process of the tubular epithelium lining the cysts. Secretion and re-absorption take place at approximately the same rate, with secretion slightly higher, so that the amount of fluid in the cysts increases slowly over time. The same process, via the secondary active chloride transport, is also involved in the secretion of fluid into the lumen of proximal tubules in teleost and elasmobranch fishes. Of interest, this process of chloride transport can be markedly inhibited by somatostatin, as demonstrated in the shark rectal gland. Recently, somatostatin analogues have become available and used with negligible side effects for long-term treatment of tumors (up to 8-12 months). To evaluate the tolerability and the safety of long-acting somatostatin in ADPKD patients, a prospective cross-over controlled study has been recently performed. This pilot study demonstrated the safety of six month treatment of long-acting somatostatin in patients with ADPKD. Moreover, the percent increase of total kidney volume was significantly lower in patients on somatostatin than in placebo. Preliminary data on late stage ADPKD also suggest that loss of renal function in these patients closely correlates with the increase in kidney volume taken by small cysts (<5 mm3), but not total cyst volume. Overall, these findings provide the basis for designing a long-term study in ADPKD patients aimed to document the efficacy of the somatostatin treatment in preventing further increase or even reducing the total kidney volume and the renal volume taken up by small cysts, eventually halting kidney disease progression. Aims The general aim of the study is to compare the effects on disease progression of three year treatment with long-acting somatostatin or placebo in patients with ADPKD and normal renal function or mild to moderate renal insufficiency. Specifically, the following aims will be pursued: Primary To compare in somatostatin and placebo ADPKD groups the change over baseline of the total kidney volume at 1 and 3 years follow-up (estimated by gadolinium contrast enhanced and T2-weighted magnetic resonance imaging, MRI). Secondary
Patients Patients enrolled in this long-term follow-up study are those with ADPKD and normal renal function or mild to moderate renal insufficiency (estimated GFR >40 ml/min/1.73 m2 by MDRD equation), no evidence of associated systemic, renal parenchymal or urinary tract disease and no specific contraindication to the study drug. |
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Study Type ICMJE | Interventional | |||
Study Phase ICMJE | Phase 3 | |||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Single (Participant) Primary Purpose: Treatment |
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Condition ICMJE | Autosomal Dominant Polycystic Kidney Disease (ADPKD) | |||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Caroli A, Perico N, Perna A, Antiga L, Brambilla P, Pisani A, Visciano B, Imbriaco M, Messa P, Cerutti R, Dugo M, Cancian L, Buongiorno E, De Pascalis A, Gaspari F, Carrara F, Rubis N, Prandini S, Remuzzi A, Remuzzi G, Ruggenenti P; ALADIN study group. Effect of longacting somatostatin analogue on kidney and cyst growth in autosomal dominant polycystic kidney disease (ALADIN): a randomised, placebo-controlled, multicentre trial. Lancet. 2013 Nov 2;382(9903):1485-95. doi: 10.1016/S0140-6736(13)61407-5. Epub 2013 Aug 21. | |||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||
Recruitment Status ICMJE | Completed | |||
Actual Enrollment ICMJE |
78 | |||
Original Enrollment ICMJE |
66 | |||
Actual Study Completion Date ICMJE | January 2012 | |||
Actual Primary Completion Date | January 2012 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 75 Years (Adult, Older Adult) | |||
Accepts Healthy Volunteers ICMJE | No | |||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||
Listed Location Countries ICMJE | Italy | |||
Removed Location Countries | ||||
Administrative Information | ||||
NCT Number ICMJE | NCT00309283 | |||
Other Study ID Numbers ICMJE | ALADIN 2005-005552-41 ( EudraCT Number ) |
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Has Data Monitoring Committee | No | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement ICMJE | Not Provided | |||
Responsible Party | Mario Negri Institute for Pharmacological Research | |||
Study Sponsor ICMJE | Mario Negri Institute for Pharmacological Research | |||
Collaborators ICMJE | Not Provided | |||
Investigators ICMJE |
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PRS Account | Mario Negri Institute for Pharmacological Research | |||
Verification Date | April 2013 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |