Ignite Creation Date:
2024-05-05 @ 4:45 PM
Last Modification Date:
2024-10-26 @ 9:24 AM
Study NCT ID:
NCT00309283
Status:
COMPLETED
Last Update Posted:
2013-04-24
First Post:
2006-03-30
Brief Title:
Somatostatin in Polycystic Kidney a Long-term Three Year Follow up Study
Sponsor:
Mario Negri Institute for Pharmacological Research
Organization:
Mario Negri Institute for Pharmacological Research
Study Overview
Official Title:
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
Status:
COMPLETED
Status Verified Date:
2013-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ALADIN
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 cystsTo 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
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 cystsTo 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
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
1 As secondary efficacy endpoints the following parameters absolute and percent change over baseline by MRI analysis will be compared in the two ADPKD groups at baseline at 1 and 3 years follow-up
Renal cyst volume
Total renal parenchymal volume
Residual renal volume
Renal parenchymal volume taken up by small cysts 5 mm3
2 Additional functional parameters will be compared in the two groups at baseline and at 1 2 3 years follow-up as follows
Systolic and diastolic blood pressure
GFR plasma iohexol clearance
GFR over baseline
RPF plasma PAH clearance
Serum creatinine concentration
Diuresis
24 h urinary protein excretion rate
24 h urinary albumin excretion rate
Protein albumin creatinine concentrations on spot morning urine samples
Protein creatinine ratio on spot morning urine samples
Albumincreatinine ratio on spot morning urine samples
Urinary sodium urea glucose phosphorus concentrations 24 hr samples
Urine osmolality calculated
3 Correlation analyses between MRI and functional parameters will be also performed
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 mlmin173 m2 by MDRD equation no evidence of associated systemic renal parenchymal or urinary tract disease and no specific contraindication to the study drug
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
1 As secondary efficacy endpoints the following parameters absolute and percent change over baseline by MRI analysis will be compared in the two ADPKD groups at baseline at 1 and 3 years follow-up
Renal cyst volume
Total renal parenchymal volume
Residual renal volume
Renal parenchymal volume taken up by small cysts 5 mm3
2 Additional functional parameters will be compared in the two groups at baseline and at 1 2 3 years follow-up as follows
Systolic and diastolic blood pressure
GFR plasma iohexol clearance
GFR over baseline
RPF plasma PAH clearance
Serum creatinine concentration
Diuresis
24 h urinary protein excretion rate
24 h urinary albumin excretion rate
Protein albumin creatinine concentrations on spot morning urine samples
Protein creatinine ratio on spot morning urine samples
Albumincreatinine ratio on spot morning urine samples
Urinary sodium urea glucose phosphorus concentrations 24 hr samples
Urine osmolality calculated
3 Correlation analyses between MRI and functional parameters will be also performed
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 mlmin173 m2 by MDRD equation no evidence of associated systemic renal parenchymal or urinary tract disease and no specific contraindication to the study drug
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2005-005552-41 | EUDRACT_NUMBER | None | None |