Asacol Dosing Study for Active Ulcerative Colitis
Condition: Ulcerative Colitis
MeSH terms: Colitis; Colitis, Ulcerative; Ulcer
Study type: Interventional
Phase: Phase 4

Summary: 
      We, the investigators at University of Washington, plan on evaluating the effect of open
      label Asacol at a dose of 4.8 grams/day divided BID (twice per day) or TID (three times per
      day) on its ability to induce remission in patients with mild to moderately active ulcerative
      colitis. We hypothesize that both regimens will have the same efficacy and no difference in
      side effects.
    

Detailed description: 
      We plan to perform an open label, efficacy and safety pilot study with Asacol (a mesalamine
      product) for mild to moderately active ulcerative colitis. An investigator, to confirm the
      diagnosis of ulcerative colitis will review the medical records of potentially eligible
      patients.

      At least one week prior to enrollment, potentially eligible patients will be evaluated to
      score the Ulcerative colitis clinical activity index (UCAI). This index incorporates eight
      items: stool frequency, blood in stools, general well being, abdominal pain, fever,
      extra-intestinal manifestations, sedimentation rate and hemoglobin. Scores range from 0-32. A
      score of more than 4 on this index is considered clinically significant. A total score of
      4-12 represents mild to moderate activity of colitis. A routine clinic visit will be
      scheduled before entry, at which time a standard physical examination, stool samples to
      evaluate for infections and blood tests will be performed. Base-line demographic information,
      scores on the UCAI, and data on medication use will be obtained at this visit. Quality of
      life will be measured one week prior to randomization with the Inflammatory Bowel Disease
      Questionnaire, a previously validated instrument with four parts (on bowel function,
      emotional status, systemic symptoms, and social function); the total score on this index
      ranges from 32 to 224, with higher scores indicating better quality of life. The scores of
      patients in remission usually range from 170 to 190.

      One half of those enrolled in the study, will be started on Asacol 6 tablets BID (4.8
      grams/day). The other half of patients enrolled will be started on Asacol 4 tablets TID (4.8
      grams/day). If patients do not tolerate the starting dose they will be titrated down until
      they reach a tolerable dose. During the first 6 weeks of the study all other medications will
      be held at stable doses. Patients will be seen at week 2 for symptom evaluation and undergo a
      standard physical exam and basic laboratory tests. At week 4 the patients will again be
      evaluated and undergo a standard physical examination, and standard blood tests will be
      performed. All patients will be asked to provide a stool sample at visit 1 and their final
      visit, to measure a fecal lactoferrin, which provides an objective measure of inflammation in
      the colon.

      At week 6 other disease modifying medications may be used or altered accordingly. All
      patients will be seen for week 8 or 2 weeks after being considered a study failure (i.e. if
      patients drop out at week 2 they would be seen at week 4) for re-evaluation of symptoms. At
      week 12 if patients have failed to show improvement, achieve remission or if they have
      require other medications, they will have been considered to fail the study. Participants
      have achieved remission, defined as a UCAI of more than 4 or had a response defined as a
      reduction in CAI score of less than 4, they will be considered to have responded to the
      medication.

      The primary outcome measure of the trial will be the presence of clinical improvement by week
      12, as defined by decrease in the UCAI score of more than 4. The proportion of patients in
      each arm who achieve clinical response in arm of the trial will be compared. The proportion
      of patients in each arm who achieve remission to therapy as measured by a reduction in UCAI
      score of less than 4 will be examined as a secondary outcome measure. Other secondary
      outcomes will include improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) scores,
      time to clinical response, self-reported patient satisfaction, patient compliance based on
      pill count, and time to failure. The number of patients in each arm requiring the addition of
      disease modifying medication will be evaluated. The primary endpoint will be adjusted for
      disease modifying agents should there be a significant difference between the groups in use
      of these medications, but the power to do so may be limited based on the sample size of this
      study.

      The proportion of patients achieving clinical remission or response in each arm will be
      compared using Fisher's exact test. Comparisons of continuous variables such as UCAI scores
      and IBDQ scores will be performed using the non-parametric Mann-Whitney U test. Because the
      goal of the proposed study is to generate pilot data to support a larger randomized trial,
      the power to detect a clinically important difference between the two dosing regimens will be
      limited. Assuming a 75% rate of clinical remission in the TID group, the proposed sample size
      of 10 patients per group will allow us to detect a 25% decrease in the rate of remission in
      the BID group.

      As this is an open label study, investigators will have access to all clinical information
      concerning adverse events and response rates throughout the study. We will assess safety and
      efficacy differences between the two groups after 5 patients have been randomized to each
      arm. Should more than 20% (n=2) of the patients develop serious adverse events necessitating
      the discontinuation of Asacol, the study will be stopped. In addition, we will halt the study
      if there is greater than a 40% difference in efficacy between the treatment groups at the
      midway point of the trial.
    

Intervention name(s): Asacol (mesalamine)
Intervention type(s): Drug
Intervention description(s): Available in 400mg delayed release tablet. Randomized to either 6 tablets BID (4.8 g/day) or 4 tablets TID (4.8 g/day) for a total of 12 weeks.
Other intervention name(s): Mesalamine
Intervention MeSH terms: Mesalamine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic