Pravastatin Therapy in Patients With Active Crohn's Disease: A Pilot Study

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2011 by University of Virginia.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
American College of Gastroenterology
Information provided by:
University of Virginia
ClinicalTrials.gov Identifier:
NCT00599625
First received: December 26, 2007
Last updated: March 4, 2011
Last verified: March 2011
  Purpose

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 Intervention
Crohn's Disease
Drug: Pravastatin

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pravastatin Therapy in Patients With Active Crohn's Disease: A Pilot Study

Resource links provided by NLM:


Further study details as provided by University of Virginia:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: October 2004
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Patients with active Crohn's Disease
Drug: Pravastatin
80mg administered daily for 6 consecutive weeks

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and non-pregnant females on an adequate contraceptive regimen aged 18-65
  • Active Crohn's disease (HBI >5 or serum CRP concentration above the upper limits of normal on initial labs.
  • Stable regimen of medications for treatment of Crohn's disease for at least 4 weeks and will continue the current regimen for the 6 weeks of drug administration. Patients taking azathioprine/6-MP and methotrexate will need to be on a stable dose of these medications for a minimum of 8 weeks prior to study enrollment.
  • Medications for the treatment of Crohn's disease meeting inclusion criteria are azathioprine/6-MP, methotrexate, mesalamine, ciprofloxacin, metronidazole, budesonide, and/or less than or equal to 20mg prednisone or an equivalent steroid per day

Exclusion Criteria:

  • Patients less than 18 or greater than 65
  • Current therapy with a statin or alternative medication for hyperlipidemia
  • Hypersensitivity or known adverse reaction to statin therapy in the past
  • Pregnancy
  • Use of cyclosporin, erythromycin, and/or greater than 20mg of prednisone or its equivalent per day during the 4 weeks prior to study entry and/or during the 6 week study drug administration period.
  • Use of infliximab during 8 weeks prior to study entry and/or during the 6 week study drug administration period.
  • AST, ALT or CK more than twice the upper limits of normal on baseline laboratory data
  • Serum creatinine greater than 1.5 or estimated creatinine clearance less than 40mL/min on baseline laboratory data.
  • Clinically significant perianal fistulae
  • Patients with diverting or end ostomy.
  • Experimental therapy for Crohn's disease in the 4 weeks prior to study entry
  • Presence of medical condition or disease that, in the opinion of the investigators, may place the patient at unacceptable risk for study participation, including, but not limited to, pregnancy, lactation, and/or inability/unwillingness to adhere to a contraceptive regimen.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00599625

Contacts
Contact: Brian Behm, MD 434-924-2959 bwb2c@virginia.edu
Contact: Sandra Oliphant 434-982-0871 slo2n@virginia.edu

Locations
United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Brian Behm, MD    434-924-2959    bwb2c@virginia.edu   
Contact: Meredith Gross    434-924-2753    mpg8b@virginia.edu   
Principal Investigator: Brian Behm, MD         
Sponsors and Collaborators
University of Virginia
American College of Gastroenterology
Investigators
Principal Investigator: Brian Behm, MD University of Virginia
  More Information

No publications provided

Responsible Party: Brian Behm, MD, University of Virginia
ClinicalTrials.gov Identifier: NCT00599625     History of Changes
Other Study ID Numbers: 11453
Study First Received: December 26, 2007
Last Updated: March 4, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by University of Virginia:
Crohn's Disease

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Pravastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 02, 2014