Pravastatin Therapy in Patients With Active Crohn's Disease: A Pilot Study
|ClinicalTrials.gov Identifier: NCT00599625|
Recruitment Status : Unknown
Verified March 2011 by University of Virginia.
Recruitment status was: Recruiting
First Posted : January 24, 2008
Last Update Posted : March 8, 2011
The primary objective of this study is to provide data regarding clinical and immunologic activity of oral doses of pravastatin 80mg administered daily for 6 consecutive weeks, for the treatment of active Crohn's disease as shown by the Harvey-Bradshaw Index (HBI) and/or elevated C-reactive protein (CRP).
We hypothesize pravastatin will significantly reduce symptoms of Crohn's disease, as shown by a decrease in HBI, by the end of the study period. Secondary outcomes of this study include the effect of pravastatin on C-reactive protein, ESR, proinflammatory cytokines, and fecal lactoferrin.
|Condition or disease||Intervention/treatment||Phase|
|Crohn's Disease||Drug: Pravastatin||Not Applicable|
The HMG CoA (3-hydroxy-3-methylglutarylcoenzyme A) reductase inhibitors (statins) have been found to significantly reduce cardiovascular morbidity and mortality (1,2). While these clinical benefits are mediated in part by changes in lipids, particularly reductions in low-density lipoproteins (LDL), recent studies have suggested broader anti-inflammatory effects may also play a role by modifying various inflammatory pathways (3). Statins inhibit the synthesis of several proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-8 (4,5). Statins have also been shown to reduce inflammation by down regulating expression of MHC II molecules (6). Statins inhibit the production of chemokines and C-reactive protein (CRP), both molecules involved in inflammation (7-9).
On the basis of this data, several investigators have evaluated the effects of statin therapy in several inflammatory diseases. Recent studies evaluating inflammatory arthritis found that statins significantly decreased inflammation in an animal model (10). Statins also appear to reduce the severity of chemically induced peritonitis in rats, primarily by interfering with leukocyte adhesion and extravasation (11).
In humans, two small studies evaluating the use of statins in patients with rheumatoid arthritis and several other autoimmune diseases found that short-term use of statins was associated with significant decreases in disease activity and biochemical markers of inflammation (12,13). A subsequent randomized, double-blinded study evaluating the role of atorvastatin in 116 patients with rheumatoid arthritis found significant reductions in the number of swollen joints and levels of several markers of inflammation, including ESR and CRP, after 6 months of therapy compared with placebo (14). This animal and human data confirm HMG CoA-reductase inhibitors play a role in modulating inflammatory pathways, and suggest statins may have significant therapeutic potential in a range of chronic inflammatory diseases.
The use of pravastatin has been shown to inhibit the development of colitis in a rat model (15). Dextran sulfate (DSS) is a chemical that causes intestinal injury when given enterally to animals, and DSS-induced colitis has been found to share many characteristics with inflammatory bowel disease. Rats given DSS typically become cachectic, develop hematochezia, and develop abnormalities of intestinal epithelial permeability. Rats do not develop intestinal injury when DSS is given concomitantly with pravastatin. Pravastatin appears to prevent intestinal injury at least in part by increased eNOS expression, which is typically degraded by DSS administration (15). This animal model suggests that statins could potentially play a role in reducing the inflammation associated with active inflammatory bowel disease, and could potentially be a safe and well tolerated adjunctive therapy for the treatment of inflammatory bowel disease.
This study is an open label pilot study designed to assess the safety and efficacy of pravastatin on patients with active Crohn's disease. Patients enrolled in the study will be given pravastatin 80mg daily for a total of six weeks. The primary endpoint will be reduction in clinical disease activity, as measured by the Harvey-Bradshaw Index (HBI). Patients will also be assessed for biochemical markers of inflammation before and at completion of the study to assess the impact of pravastatin on these markers.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pravastatin Therapy in Patients With Active Crohn's Disease: A Pilot Study|
|Study Start Date :||October 2004|
|Estimated Primary Completion Date :||December 2011|
|Estimated Study Completion Date :||December 2011|
Patients with active Crohn's Disease
80mg administered daily for 6 consecutive weeks
- Primary outcome will be clinical benefit which will be defined as a decrease in HBI, fecal lactoferrin, CRP and/or ESR at 6 weeks compared with baseline values [ Time Frame: 6 weeks ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00599625
|Contact: Brian Behm, MDemail@example.com|
|Contact: Sandra Oliphantfirstname.lastname@example.org|
|United States, Virginia|
|University of Virginia||Recruiting|
|Charlottesville, Virginia, United States, 22908|
|Contact: Brian Behm, MD 434-924-2959 email@example.com|
|Contact: Meredith Gross 434-924-2753 firstname.lastname@example.org|
|Principal Investigator: Brian Behm, MD|
|Principal Investigator:||Brian Behm, MD||University of Virginia|