Crohn's DiseaseNCT00599625
Pravastatin Therapy in Patients With Active Crohn's Disease: A Pilot Study
A study testing Pravastatin in people with Crohn's Disease, run by University of Virginia at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Crohn's Disease
- What is being tested?
- Pravastatin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2004to Dec 2011
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 12Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
University of Virginia
Charlottesville, Virginia, 22908
Brian Behm, MD, 434-924-2959, bwb2c@virginia.edu
Meredith Gross, 434-924-2753, mpg8b@virginia.edu
About this study
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.
Read the 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.
- Conditions
- Crohn's Disease
- Being tested
- Pravastatin
- Keywords
- Crohn's Disease
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PravastatinDrug
80mg administered daily for 6 consecutive weeks
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Patients with active Crohn's Disease Receives: Drug: Pravastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2008 (estimated)
- Study startOct 2004
- Primary completionDec 2011 (estimated)
- Study completionDec 2011 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crohn's DiseaseStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Collaborators
- American College of Gastroenterology
- Investigators
- Brian Behm, MD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00599625
- Sponsor's protocol ID
- 11453
- Status last verified
- Mar 2011
- First submitted
- 26 Dec 2007
- Last updated
- 8 Mar 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pravastatin Therapy in Patients With Active Crohn's Disease: A Pilot Study
- ClinicalTrials.gov ID
- NCT00599625
- Acronym / sponsor ID
- 11453
- Conditions
- Crohn's Disease
- Keywords
- Crohn's Disease
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- American College of Gastroenterology
- Study start
- Oct 2004
- Primary completion
- Dec 2011 (estimated)
- Study completion
- Dec 2011 (estimated)
- First posted
- 24 Jan 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: PravastatinPatients with active Crohn's Disease |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pravastatin80mg administered daily for 6 consecutive weeks | Drug | 1 |
Primary outcome
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2011.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brian Behm, MD principal investigator
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pravastatin in people with Crohn's Disease, run by University of Virginia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Mar 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Brian Behm, MD (434-924-2959, bwb2c@virginia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2011.