Ignite Creation Date:
2024-05-05 @ 6:35 PM
Last Modification Date:
2024-10-26 @ 9:35 AM
Study NCT ID:
NCT00512967
Status:
COMPLETED
Last Update Posted:
2017-02-24
First Post:
2007-07-19
Brief Title:
The Occurence of Inflammation and Oxidative Stress in Lung Diseases
Sponsor:
Maastricht University Medical Center
Organization:
Maastricht University Medical Center
Study Overview
Official Title:
The Inflammatory and Antioxidant Status in Pulmonary Sarcoidosis Idiopathic Pulmonary Fibrosis and COPD a Potential Role for Antioxidants
Status:
COMPLETED
Status Verified Date:
2008-02
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:
None
Brief Summary:
Reactive oxygen species ROS are suggested to play a pivotal role in ILD Little is known however about the endogenous antioxidant levels in ILD that can offer protection against ROS It is expected that the high amount of ROS present in ILD will reduce the antioxidant levels Therefore antioxidant therapy to strengthen this reduced antioxidant defense might be efficacious in ILD treatment Since ROS are capable of initiating and mediating inflammation antioxidant therapy might also mitigate elevated inflammation A candidate for antioxidant therapy is the flavonoid quercetin that is known for its anti-oxidative and anti-inflammatory capacities
The aim of the present study is to determine the antioxidant and inflammatory status in ILD ie sarcoidosis and idiopathic pulmonary fibrosis IPF Furthermore to evaluate the possible anti-inflammatory effects of antioxidants the effect of quercetin will be examined on the ex vivo LPS-induced cytokine production in ILD
The aim of the present study is to determine the antioxidant and inflammatory status in ILD ie sarcoidosis and idiopathic pulmonary fibrosis IPF Furthermore to evaluate the possible anti-inflammatory effects of antioxidants the effect of quercetin will be examined on the ex vivo LPS-induced cytokine production in ILD
Detailed Description:
Interstitial lung diseases ILD include various chronic lung disorders such as sarcoidosis and idiopathic lung fibrosis IPF In the Netherlands the incidence of sarcoidosis is approximately 20-25 per 100000 inhabitants whereas that of IPF is approximately 1000-1500 new cases each year
In short three different stages in the development of ILD can be discerned Firstly the lung tissue is damaged In sarcoidosis this damage is thought to be antigen-driven multisystemically and leading to the formation of granuloma Moreover it is suggested that genetic factors play an important role in the genesis of sarcoidosis In IPF the exact etiology of this damage is unknown but it has been speculated to be inflicted by an unidentified stimulus that produces repeated episodes of acute lung injury Secondly the walls of the air sacs in the lung become inflamed as a reaction to the caused damage This results in the activation of inflammatory cells like macrophages that cause the expression of pro-inflammatory cytokines especially interleukin-10 and tumour necrosis factor TNF-alpha in the lungs
Finally scarring or fibrosis begins in the interstitium or tissue between the air sacs and the lung becomes stiff causing an irreversible loss of the tissues ability to transfer oxygen
It is well-known that inflammation plays a key-role in the occurrence and progression of ILD although the long-lasting hypothesis that inflammation alone leads to fibrosis is being questioned at the moment Conventional treatment of ILD comprises nonspecific anti-inflammatory agents such as glucocorticoids prednisone and other immune-suppressing medication such as cyclophosphamide methotrexate and gamma-interferon However all these therapies fail to be completely efficacious suggesting that inflammation alone is indeed not solely responsible for the occurrence and progression of ILD Paradoxically anti-TNF-α agents such as infliximab and thalidomide have recently shown some beneficial effects in sarcoidosis
A pivotal role for reactive oxygen species ROS in all three stages has also been proposed Various biomarkers of oxidative stress ie exhaled ethane and both 8-isoprostane and oxidized proteins in the bronchoalveolar fluid are elevated in ILD patients of different clinical stages However only little is known about the effect of this elevated oxidative stress on the endogenous antioxidant levels present in ILD Interestingly clinical administration of an antioxidant ie N-acetylcysteine NAC to IPF patients has recently demonstrated that this slows the deterioration of vital capacity and carbon monoxide diffusing capacity DLCO at 12 months This supports the hypothesis that oxidative stress is involved in ILD and proofs the principle of antioxidant treatment in ILD
It is well-known that oxidative stress and inflammation are intertwined and that the pro-inflammatory cytokine TNF-alpha is capable of stimulating oxidative stress in various cells and tissues As a result the preliminary beneficial effects of anti-TNF-alpha agents combined with the preliminary beneficial effects of antioxidants in ILD may indicate that a new strategy of treatment of ILD should ideally combine the reduction of both the oxidative stress and the inflammation occurring in these diseases
Recently much attention has been given to the potential health-beneficial properties of flavonoids natural occurring polyphenolic compounds and to quercetin the most commonly occurring flavonoid in particular Quercetin is known to be a powerful antioxidant and to possess some anti-inflammatory effects It is therefore tempting to speculate that quercetin could exert positive effects in ILD
Since the anti-oxidative and inflammatory changes in ILD are still not exactly known the aim of the present study is to determine both the anti-oxidant and the inflammatory status in ILD ie sarcoidosis and fibrosis Furthermore the possible anti-inflammatory effect of antioxidants on LPS-induced cytokine production exemplified with the flavonoid quercetin will be examined
In short three different stages in the development of ILD can be discerned Firstly the lung tissue is damaged In sarcoidosis this damage is thought to be antigen-driven multisystemically and leading to the formation of granuloma Moreover it is suggested that genetic factors play an important role in the genesis of sarcoidosis In IPF the exact etiology of this damage is unknown but it has been speculated to be inflicted by an unidentified stimulus that produces repeated episodes of acute lung injury Secondly the walls of the air sacs in the lung become inflamed as a reaction to the caused damage This results in the activation of inflammatory cells like macrophages that cause the expression of pro-inflammatory cytokines especially interleukin-10 and tumour necrosis factor TNF-alpha in the lungs
Finally scarring or fibrosis begins in the interstitium or tissue between the air sacs and the lung becomes stiff causing an irreversible loss of the tissues ability to transfer oxygen
It is well-known that inflammation plays a key-role in the occurrence and progression of ILD although the long-lasting hypothesis that inflammation alone leads to fibrosis is being questioned at the moment Conventional treatment of ILD comprises nonspecific anti-inflammatory agents such as glucocorticoids prednisone and other immune-suppressing medication such as cyclophosphamide methotrexate and gamma-interferon However all these therapies fail to be completely efficacious suggesting that inflammation alone is indeed not solely responsible for the occurrence and progression of ILD Paradoxically anti-TNF-α agents such as infliximab and thalidomide have recently shown some beneficial effects in sarcoidosis
A pivotal role for reactive oxygen species ROS in all three stages has also been proposed Various biomarkers of oxidative stress ie exhaled ethane and both 8-isoprostane and oxidized proteins in the bronchoalveolar fluid are elevated in ILD patients of different clinical stages However only little is known about the effect of this elevated oxidative stress on the endogenous antioxidant levels present in ILD Interestingly clinical administration of an antioxidant ie N-acetylcysteine NAC to IPF patients has recently demonstrated that this slows the deterioration of vital capacity and carbon monoxide diffusing capacity DLCO at 12 months This supports the hypothesis that oxidative stress is involved in ILD and proofs the principle of antioxidant treatment in ILD
It is well-known that oxidative stress and inflammation are intertwined and that the pro-inflammatory cytokine TNF-alpha is capable of stimulating oxidative stress in various cells and tissues As a result the preliminary beneficial effects of anti-TNF-alpha agents combined with the preliminary beneficial effects of antioxidants in ILD may indicate that a new strategy of treatment of ILD should ideally combine the reduction of both the oxidative stress and the inflammation occurring in these diseases
Recently much attention has been given to the potential health-beneficial properties of flavonoids natural occurring polyphenolic compounds and to quercetin the most commonly occurring flavonoid in particular Quercetin is known to be a powerful antioxidant and to possess some anti-inflammatory effects It is therefore tempting to speculate that quercetin could exert positive effects in ILD
Since the anti-oxidative and inflammatory changes in ILD are still not exactly known the aim of the present study is to determine both the anti-oxidant and the inflammatory status in ILD ie sarcoidosis and fibrosis Furthermore the possible anti-inflammatory effect of antioxidants on LPS-induced cytokine production exemplified with the flavonoid quercetin will be examined
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