Ignite Creation Date:
2024-05-05 @ 11:49 PM
Last Modification Date:
2024-10-26 @ 10:40 AM
Study NCT ID:
NCT01425242
Status:
TERMINATED
Last Update Posted:
2014-12-09
First Post:
2011-08-26
Brief Title:
Study on Anti-inflammatory Effect of Anti-hypertensive Treatment in Patients With Small AAAs and Mild Hypertension
Sponsor:
Amsterdam UMC location VUmc
Organization:
Amsterdam UMC location VUmc
Study Overview
Official Title:
An Open-label PET-observer-blinded Pilot Study of the Effect of Aliskiren- Versus Amlodipine-based Antihypertensive Treatment in Patients With Small Abdominal Aortic Aneurysm and Mild to Moderate Hypertension on Aneurysmal FDG-uptake
Status:
TERMINATED
Status Verified Date:
2014-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Insufficient number of participants
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PISA
Brief Summary:
Inflammation of the blood vessel plays an important role in the development and growth of a dilated abdominal aorta An elevated blood pressure leads to an increase in inflammation therefore blood pressure lowering is an important part of the treatment of patients with a dilated abdominal aorta who also have an elevated blood pressure In the investigators study the investigators compare the anti-inflammatory effects of 2 different blood pressure lowering strategies The investigators hypothesize that both strategies will decrease inflammation however the investigators believe the total decrease of inflammation depends on the type of blood pressure lowering medication used
Detailed Description:
Standard therapy of small AAAs currently consists of watchful waiting strategy with aggressive blood pressure control Watchful waiting includes an Ultrasound more recently CT or MRI scan every 12 months for AAAs between 35 - 44 cm or every 6 months for AAAs between 45 and 55 cm to observe A growth rate of 7 mm 6 months has been suggested as a threshold for proceeding to aneurysm repair irrespective of aneurysm size Clearly there is need for a more sensitive method to evaluate the progress of AAA growth
Recent publications have shown that evaluation of AAAs using FDG-uptake with PET-scan may identify small AAAs that are more prone to grow andor rupture as these AAAs as compared to normal aortas show increased inflammatory activity which is considered the major pathophysiological pathway Evaluation of FDG-uptake is also sensitive enough to observe the short-term effects of endovascular intervention of large AAAs as unpublished data show a statistically significant reduction in aneurismal FDG-uptake only 6 weeks after endovascular repair of large AAAs Therefore the change in aneurismal FDG-uptake may also be a very promising and sensitive method to evaluate treatment effects of medical interventions within a relatively short period of time 3 months
Just as pressure unloading may represent an anti-inflammatory mechanism in endovascular repair of more advanced aneurysms so may milder pressure unloading in moderately hypertensive individuals with smaller aneurysms display similar anti-inflammatory effects Such a mild form of pressure unloading may be attainable with adequate anti-hypertensive drug therapy In this context however a possible additional benefit may be that some anti-hypertensive drug classes have been proposed to exert specific anti-inflammatory effects relevant to aneurysm inflammation
Local activation of multiple components of the renin angiotensin system has been implicated in both the development of aneurysms as well as in their inflammatory component In accordance preliminary evidence from murine studies suggest that ACE inhibitors for example may reduce inflammatory activity in aneurysmatic vessel walls However since ACE inhibitors block the renin angiotensin system halfway its path and non-ACE conversion of angiotensin I occurs a rationale exists to block the renin angiotensin system upstream of ACE Upstream blockade of the renin-angiotensin system may have additional advantages in antagonising direct pro-inflammatory effects of renin itself which have been identified in for example kidney tissue and retinal microvessels
A case can thus be made for renin inhibition as a potential optimal strategy for reducing aneurysm inflammation in hypertensive patients with aortic aneurysms In the proposed pilot trial the direct renin inhibitor Aliskiren will be evaluated As a control condition an antihypertensive agent without postulated specific anti-inflammatory effects is appropriate Calcium channel blockers represent such a class
The current study will explore what the size and variability of the effect of aliskiren monotherapy the combination of aliskirenhydrochlorothiazide amlodipine monotherapy or the combination of amlodipinehydrochlorothiazide on FDG-uptake is if at all measurable on top of the effect of antihypertensive and statin therapy This will allow more accurate power calculation of larger future studies aiming at prevention of AAA-progression diameter and rupture
Recent publications have shown that evaluation of AAAs using FDG-uptake with PET-scan may identify small AAAs that are more prone to grow andor rupture as these AAAs as compared to normal aortas show increased inflammatory activity which is considered the major pathophysiological pathway Evaluation of FDG-uptake is also sensitive enough to observe the short-term effects of endovascular intervention of large AAAs as unpublished data show a statistically significant reduction in aneurismal FDG-uptake only 6 weeks after endovascular repair of large AAAs Therefore the change in aneurismal FDG-uptake may also be a very promising and sensitive method to evaluate treatment effects of medical interventions within a relatively short period of time 3 months
Just as pressure unloading may represent an anti-inflammatory mechanism in endovascular repair of more advanced aneurysms so may milder pressure unloading in moderately hypertensive individuals with smaller aneurysms display similar anti-inflammatory effects Such a mild form of pressure unloading may be attainable with adequate anti-hypertensive drug therapy In this context however a possible additional benefit may be that some anti-hypertensive drug classes have been proposed to exert specific anti-inflammatory effects relevant to aneurysm inflammation
Local activation of multiple components of the renin angiotensin system has been implicated in both the development of aneurysms as well as in their inflammatory component In accordance preliminary evidence from murine studies suggest that ACE inhibitors for example may reduce inflammatory activity in aneurysmatic vessel walls However since ACE inhibitors block the renin angiotensin system halfway its path and non-ACE conversion of angiotensin I occurs a rationale exists to block the renin angiotensin system upstream of ACE Upstream blockade of the renin-angiotensin system may have additional advantages in antagonising direct pro-inflammatory effects of renin itself which have been identified in for example kidney tissue and retinal microvessels
A case can thus be made for renin inhibition as a potential optimal strategy for reducing aneurysm inflammation in hypertensive patients with aortic aneurysms In the proposed pilot trial the direct renin inhibitor Aliskiren will be evaluated As a control condition an antihypertensive agent without postulated specific anti-inflammatory effects is appropriate Calcium channel blockers represent such a class
The current study will explore what the size and variability of the effect of aliskiren monotherapy the combination of aliskirenhydrochlorothiazide amlodipine monotherapy or the combination of amlodipinehydrochlorothiazide on FDG-uptake is if at all measurable on top of the effect of antihypertensive and statin therapy This will allow more accurate power calculation of larger future studies aiming at prevention of AAA-progression diameter and rupture
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 |
|---|---|---|---|
| 2011-000538-12 | EUDRACT_NUMBER | None | None |