Crohn's DiseasePhase 3NCT00098111
Imuran (Azathioprine) Dose-Ranging Study in Crohn's Disease
A Phase 3 study testing azathioprine in people with Crohn's Disease, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
The purpose of this study is to identify an optimal weight based dose of azathioprine that is safe and effective in the treatment of subjects with active Crohn's disease requiring treatment with corticosteroids, and for maintaining remission in those subjects. Read more about this study
- Who is it for?
- Ages 14 years and older
- Conditions the study is for
- Crohn's Disease
- What is being tested?
- azathioprine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2005to Jul 2007
- Phase
- Phase 3
- 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 14 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Males and females ≥ 14 years old, including women of childbearing potential who are not pregnant or nursing at the time of enrollment.
- Body weight between 40 and 100 kg (88-220 lbs), inclusive.
- Subjects diagnosed with Crohn's disease, based upon the criteria of Lennard-Jones, for at least a 3-month period. The date of diagnosis will be the date of the first diagnostic test that confirms the diagnosis of Crohn's disease. Subjects with a diagnosis of less than 3 months may be considered after review of primary diagnostic data by the study safety monitor.
- Need for treatment with oral prednisone, based upon the treating physician's clinical judgment, for active Crohn's disease as indicated by a (Crohn's Disease Activity Index) CDAI between 200 and 450, inclusive; OR Currently being treated with prednisone for at least 4 weeks with a stable dose of 40mg/day or less for at least 2 weeks, or budesonide (Entocort EC) 9 mg/day for at least 4 weeks with a stable dose for at least 4 weeks, and active Crohn's disease as indicated by a CDAI between 200 and 450, inclusive.
- Able to swallow tablets.
- Able to provide written informed consent (subjects ≥ 18 years old) or in the case of a minor provide parental consent along with child assent (subjects 14-17 years old).
- If sexually active, willing to comply with effective contraception during the study; or is abstinent.
Who cannot join
- Diagnosis of indeterminate, microscopic, lymphocytic, collagenous, or ulcerative colitis.
- Previous or current therapy with 6-mercaptopurine, azathioprine, thioguanine, methotrexate, cyclosporine, tacrolimus, thalidomide or mycophenolate mofetil.
- Previous or current treatment with infliximab.
- Treatment with narcotic pain medications. (Anti-diarrheal agents such as loperamide and diphenoxylate are permitted, providing that the dose is not increased while on protocol.)
- Subjects with short gut syndrome (defined as requiring oral or parenteral supplemental or total nutrition in order to maintain stable body weight, or more than 100 cm of small bowel resected).
- Subjects with obstructive symptoms or demonstrated stenosis and prestenotic dilatation on barium study.
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- Subjects with active infection.
- Subjects with a stoma.
- Subjects with heterozygous or recessive homozygous genotype for TPMT.
- Poor access for peripheral venous phlebotomy.
- History of pancreatitis, except for self-limited episodes from a known cause, such as gallstone pancreatitis.
- White blood cell count (WBC) <4.5 x 10^9/L, hemoglobin <8 gm/dL, Platelets (PLT) <100,000/mm3 at screening (or within the previous 6 months, if known).
- History of abnormal liver function tests, including aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 times upper limit of normal, alkaline phosphatase >2 times upper limit of normal, total bilirubin >2.5 mg/dL at screening (or within the previous 6 months, if known).
- Subjects needing treatment with orally administered corticosteroids for the treatment of other medical conditions. Inhaled or dermatologic preparations are acceptable.
- History of HIV infection (if known) or opportunistic infection.
- History of cancer, with the exception of basal cell carcinoma of the skin.
- Concurrent treatment, or need for treatment, with allopurinol.
- Women who are pregnant or nursing at the time of eligibility screening, or who intend to be during the study period.
- Inability to comply with planned schedule of study visits.
- Participation in a clinical trial within the past 6 months.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: A Double-Blinded, Randomized, Parallel Arm, Dose Ranging Study of IMURAN in Subjects With Active Crohn's Disease Requiring Treatment With Prednisone: A Crohn's Disease Optimal Range Dose of IMURAN Study (ACORDIS)
The purpose of this study is to identify an optimal weight based dose of azathioprine that is safe and effective in the treatment of subjects with active Crohn's disease requiring treatment with corticosteroids, and for maintaining remission in those subjects.
Read the detailed description
DESCRIPTION: Medical therapy for Crohn's disease is of variable success in ameliorating the cardinal symptoms of the disease (diarrhea, abdominal pain), in treating extraintestinal manifestations (fatigue, anorexia, fever, weight loss, arthralgias, skin, eye, liver and kidney manifestations), and in preventing complications (stricture, fistula, abscess). Currently, therapy is most often implemented in a stepwise fashion, progressing through anti-inflammatory medications (sulfasalazine, mesalamine), antibiotics (metronidazole, ciprofloxacin), corticosteroids, immunomodulatory or immunosuppressive medications, including thioguanine compounds (6 mercaptopurine or its prodrug azathioprine), methotrexate, and finally, infliximab (anti-tumor necrosis factor). A common approach is the gradual addition of more potent medications to agents that are believed to be safer, but may also be less effective. Despite the current approach to medical therapy in Crohn's disease, a substantial number of patients-from 20 to 40%-require surgery within 3 years of diagnosis, excluding those requiring surgery at the time of diagnosis. Nearly 80% of patients require surgery by 20 years from the onset of disease.
Corticosteroids have long been a mainstay of therapy in Crohn's disease although side effects are frequently observed with both short term and long-term use. Potential side effects are well-described, and may include relatively minor problems such as insomnia and acne, as well as more serious adverse effects, including hypertension, narrow-angle glaucoma, depression, weight gain, adrenal suppression, Cushing's syndrome, diminished bone mineral density, and infections.
Azathioprine is often used to treat patients with steroid resistant or dependent Crohn's disease. Azathioprine is used as a steroid sparing agent, as treatment for active, inflammatory disease, for maintenance of remission, as therapy for perforating disease (fistulae), and for specific extraintestinal manifestations. To date, however, randomized, controlled clinical studies assessing a range of doses of azathioprine in Crohn's disease have not been conducted. The optimal weight-based dose is not known.
EXPECTED CONTRIBUTION: This study will identify an optimal weight based dose of azathioprine for treatment of patients with active Crohn's disease requiring treatment with corticosteroids.
STUDY HYPOTHESIS: An optimal weight-based dose of azathioprine will induce and maintain remission in subjects with steroid-dependent Crohn's disease.
COMPARISON: Three different doses of azathioprine will be compared in this study (0.5, 2.5, and 3.5mg/kg/day). Subjects will take the study medication for 9 months.
- Conditions
- Crohn's Disease
- Being tested
- azathioprine
- Keywords
- Crohn's disease, inflammatory bowel disease, IMURAN, azathioprine
- Medical subject headings
- Crohn Disease, Inflammatory Bowel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
azathioprineDrug
| Study group | Role | What they receive |
|---|---|---|
| Azathioprine 0.5 mg/kg body weight | Active comparator | Not described Receives: Drug: azathioprine |
| Azathioprine 2.5 mg/kg body weight | Active comparator | Not described Receives: Drug: azathioprine |
| Azathioprine 3.5 mg/kg body weight | Active comparator | Not described Receives: Drug: azathioprine |
What is being measured
The primary outcome is the main question the study is designed to answer.
To identify an optimal weight-based dose of azathioprine for the treatment of active Crohn's disease and for maintaining remission in those subjects.
Secondary outcomes (5)
To characterize prospectively the predictive value of erythrocyte thioguanine nucleotide levels for response to azathioprine in who are wild type for the (thiopurine methyltransferase) TPMT gene
To explore the relationship of 6-thioguanine (TGN) levels to TPMT enzyme activity
To determine the effect of azathioprine dose upon time to relapse among subjects in remission induced by a course of prednisone
To prospectively determine the rate of adverse events associated with a range of doses of azathioprine
To preliminarily identify genetic polymorphisms associated with therapeutic response or toxicity to azathioprine.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2004 (estimated)
- Study startApr 2005
- Primary completionJul 2007
- Study completionJul 2007
Why it stopped: Lack of recruitment
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 Massachusetts General HospitalThe 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 3
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bruce Sands, Massachusetts General Hospital
- Investigators
- Bruce E Sands, M.D.,M.S., Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00098111
- Sponsor's protocol ID
- FD-R-02555-01
- Other IDs
- Grant # 2555
- Status last verified
- Feb 2014
- First submitted
- 3 Dec 2004
- Last updated
- 21 Feb 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blinded, Randomized, Parallel Arm, Dose Ranging Study of IMURAN in Subjects With Active Crohn's Disease Requiring Treatment With Prednisone: A Crohn's Disease Optimal Range Dose of IMURAN Study (ACORDIS)
- ClinicalTrials.gov ID
- NCT00098111
- Acronym / sponsor ID
- FD-R-02555-01
- Conditions
- Crohn's Disease
- Keywords
- Crohn's disease, inflammatory bowel disease, IMURAN, azathioprine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of recruitment
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- Apr 2005
- Primary completion
- Jul 2007 (actual)
- Study completion
- Jul 2007 (actual)
- First posted
- 6 Dec 2004 (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 purpose of this study is to identify an optimal weight based dose of azathioprine that is safe and effective in the treatment of subjects with active Crohn's disease requiring treatment with corticosteroids, and for maintaining remission in those subjects.
Detailed description
DESCRIPTION: Medical therapy for Crohn's disease is of variable success in ameliorating the cardinal symptoms of the disease (diarrhea, abdominal pain), in treating extraintestinal manifestations (fatigue, anorexia, fever, weight loss, arthralgias, skin, eye, liver and kidney manifestations), and in preventing complications (stricture, fistula, abscess). Currently, therapy is most often implemented in a stepwise fashion, progressing through anti-inflammatory medications (sulfasalazine, mesalamine), antibiotics (metronidazole, ciprofloxacin), corticosteroids, immunomodulatory or immunosuppressive medications, including thioguanine compounds (6 mercaptopurine or its prodrug azathioprine), methotrexate, and finally, infliximab (anti-tumor necrosis factor). A common approach is the gradual addition of more potent medications to agents that are believed to be safer, but may also be less effective. Despite the current approach to medical therapy in Crohn's disease, a substantial number of patients-from 20 to 40%-require surgery within 3 years of diagnosis, excluding those requiring surgery at the time of diagnosis. Nearly 80% of patients require surgery by 20 years from the onset of disease.
Corticosteroids have long been a mainstay of therapy in Crohn's disease although side effects are frequently observed with both short term and long-term use. Potential side effects are well-described, and may include relatively minor problems such as insomnia and acne, as well as more serious adverse effects, including hypertension, narrow-angle glaucoma, depression, weight gain, adrenal suppression, Cushing's syndrome, diminished bone mineral density, and infections.
Azathioprine is often used to treat patients with steroid resistant or dependent Crohn's disease. Azathioprine is used as a steroid sparing agent, as treatment for active, inflammatory disease, for maintenance of remission, as therapy for perforating disease (fistulae), and for specific extraintestinal manifestations. To date, however, randomized, controlled clinical studies assessing a range of doses of azathioprine in Crohn's disease have not been conducted. The optimal weight-based dose is not known.
EXPECTED CONTRIBUTION: This study will identify an optimal weight based dose of azathioprine for treatment of patients with active Crohn's disease requiring treatment with corticosteroids.
STUDY HYPOTHESIS: An optimal weight-based dose of azathioprine will induce and maintain remission in subjects with steroid-dependent Crohn's disease.
COMPARISON: Three different doses of azathioprine will be compared in this study (0.5, 2.5, and 3.5mg/kg/day). Subjects will take the study medication for 9 months.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Azathioprine 0.5 mg/kg body weight | Active comparator | Drug: azathioprine |
| Azathioprine 2.5 mg/kg body weight | Active comparator | Drug: azathioprine |
| Azathioprine 3.5 mg/kg body weight | Active comparator | Drug: azathioprine |
Who may qualify
- Ages
- 14 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Males and females ≥ 14 years old, including women of childbearing potential who are not pregnant or nursing at the time of enrollment.
- Body weight between 40 and 100 kg (88-220 lbs), inclusive.
- Subjects diagnosed with Crohn's disease, based upon the criteria of Lennard-Jones, for at least a 3-month period. The date of diagnosis will be the date of the first diagnostic test that confirms the diagnosis of Crohn's disease. Subjects with a diagnosis of less than 3 months may be considered after review of primary diagnostic data by the study safety monitor.
- Need for treatment with oral prednisone, based upon the treating physician's clinical judgment, for active Crohn's disease as indicated by a (Crohn's Disease Activity Index) CDAI between 200 and 450, inclusive; OR Currently being treated with prednisone for at least 4 weeks with a stable dose of 40mg/day or less for at least 2 weeks, or budesonide (Entocort EC) 9 mg/day for at least 4 weeks with a stable dose for at least 4 weeks, and active Crohn's disease as indicated by a CDAI between 200 and 450, inclusive.
- Able to swallow tablets.
Key exclusion criteria (20 listed)
- Diagnosis of indeterminate, microscopic, lymphocytic, collagenous, or ulcerative colitis.
- Previous or current therapy with 6-mercaptopurine, azathioprine, thioguanine, methotrexate, cyclosporine, tacrolimus, thalidomide or mycophenolate mofetil.
- Previous or current treatment with infliximab.
- Treatment with narcotic pain medications. (Anti-diarrheal agents such as loperamide and diphenoxylate are permitted, providing that the dose is not increased while on protocol.)
- Subjects with short gut syndrome (defined as requiring oral or parenteral supplemental or total nutrition in order to maintain stable body weight, or more than 100 cm of small bowel resected).
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 |
|---|---|---|
| azathioprine | Drug | Azathioprine 0.5 mg/kg body weight, Azathioprine 2.5 mg/kg body weight, Azathioprine 3.5 mg/kg body weight |
Primary outcome
To identify an optimal weight-based dose of azathioprine for the treatment of active Crohn's disease and for maintaining remission in those subjects.
5 secondary outcomes
To characterize prospectively the predictive value of erythrocyte thioguanine nucleotide levels for response to azathioprine in who are wild type for the (thiopurine methyltransferase) TPMT gene
To explore the relationship of 6-thioguanine (TGN) levels to TPMT enzyme activity
To determine the effect of azathioprine dose upon time to relapse among subjects in remission induced by a course of prednisone
To prospectively determine the rate of adverse events associated with a range of doses of azathioprine
To preliminarily identify genetic polymorphisms associated with therapeutic response or toxicity to azathioprine.
Results and safety
The study was stopped early (reason given: Lack of recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2014.
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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.
Bruce E Sands, M.D.,M.S. principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing azathioprine in people with Crohn's Disease, run by Massachusetts General Hospital 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 7 inclusion and 20 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: stopped early, as of the sponsor's last update on 21 Feb 2014. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Lack of recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To identify an optimal weight-based dose of azathioprine for the treatment of active Crohn's disease and for maintaining remission in those subjects.. 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 21 Feb 2014.