Trial Outcomes & Findings for Efficacy of Mesalamine in Diarrhea-predominant Irritable Bowel Syndrome (dIBS) (NCT NCT01327300)
NCT ID: NCT01327300
Last Updated: 2014-02-12
Results Overview
Patients rated the severity of their GI symptoms. The GIS scale goes from 1 to 7 with 1 being the worse and 7 as the best score showing improvement in symptoms. The GIS was performed at week one and at week 12 during each of the interventions. The comparisons below list the mean difference for each intervention from baseline (BL) with standard deviations then we list the p-value for the differences of baseline to intervention are reported using the Mann-Whitney test with a two-tailed p value provided.
COMPLETED
PHASE2
7 participants
Baseline and at 12 weeks post-intervention
2014-02-12
Participant Flow
Participants were recruited from the gastroenterology specialty clinics at the University of Florida or by referral from other primary care physicians. Recruitment was from 2011 until March, 2012
A washout period of 3 weeks was given between treatment periods with 2 weeks prior to recruitment.
Participant milestones
| Measure |
Mesalamine Then Placebo
This group received the drug Mesalamine for 12 weeks then a wash out for 3 weeks prior to crossing over to the placebo arm.
Mesalamine : Apriso is a 5-ASA drug with Intellicor ™ extended-release delivery technology. A 1.5 gram dosage of Apriso (equaling four 375 mg capsules) once a day will be administered orally for a period of 12 weeks followed by a 3 week wash out prior to crossing over to the placebo arm.
|
Placebo Then Mesalamine
This group will receive the Placebo for 12 weeks then a wash out for 3 weeks prior to crossing over to the drug arm.
Placebo : 4 capsules (.375 gm sugar pill capsules) administered orally once a day. This group will receive the placebo for 12 weeks then a wash out for 3 weeks prior to crossing over to the drug arm.
|
|---|---|---|
|
First Intervention (12 Weeks)
STARTED
|
5
|
2
|
|
First Intervention (12 Weeks)
COMPLETED
|
5
|
2
|
|
First Intervention (12 Weeks)
NOT COMPLETED
|
0
|
0
|
|
Washout (3 Weeks)
STARTED
|
5
|
2
|
|
Washout (3 Weeks)
COMPLETED
|
4
|
2
|
|
Washout (3 Weeks)
NOT COMPLETED
|
1
|
0
|
|
Second Intervention (12 Weeks)
STARTED
|
4
|
2
|
|
Second Intervention (12 Weeks)
COMPLETED
|
4
|
2
|
|
Second Intervention (12 Weeks)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Mesalamine Then Placebo
This group received the drug Mesalamine for 12 weeks then a wash out for 3 weeks prior to crossing over to the placebo arm.
Mesalamine : Apriso is a 5-ASA drug with Intellicor ™ extended-release delivery technology. A 1.5 gram dosage of Apriso (equaling four 375 mg capsules) once a day will be administered orally for a period of 12 weeks followed by a 3 week wash out prior to crossing over to the placebo arm.
|
Placebo Then Mesalamine
This group will receive the Placebo for 12 weeks then a wash out for 3 weeks prior to crossing over to the drug arm.
Placebo : 4 capsules (.375 gm sugar pill capsules) administered orally once a day. This group will receive the placebo for 12 weeks then a wash out for 3 weeks prior to crossing over to the drug arm.
|
|---|---|---|
|
Washout (3 Weeks)
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Efficacy of Mesalamine in Diarrhea-predominant Irritable Bowel Syndrome (dIBS)
Baseline characteristics by cohort
| Measure |
All Study Participants
n=7 Participants
All participants were randomized to receive both mesalamine and placebo.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
7 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
32 years
STANDARD_DEVIATION 11.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
7 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and at 12 weeks post-interventionPopulation: The first part of the analysis compares the differences between baseline and mesalamine to baseline and placebo. The P value provided below list the comparison of baseline-placebo to baseline-mesalamine using the Mann-Whitney statistical analysis.
Patients rated the severity of their GI symptoms. The GIS scale goes from 1 to 7 with 1 being the worse and 7 as the best score showing improvement in symptoms. The GIS was performed at week one and at week 12 during each of the interventions. The comparisons below list the mean difference for each intervention from baseline (BL) with standard deviations then we list the p-value for the differences of baseline to intervention are reported using the Mann-Whitney test with a two-tailed p value provided.
Outcome measures
| Measure |
Mesalamine
n=7 Participants
This group received the drug Mesalamine for 12 weeks Mesalamine : Apriso is a 5-ASA drug with Intellicor ™ extended-release delivery technology. A 1.5 gram dosage of Apriso (equaling four 375 mg capsules) once a day will be administered orally for a period of 12 weeks
|
Placebo
n=6 Participants
This group will receive the Placebo for 12 weeks.
Placebo : 4 capsules (.375 gm sugar pill capsules) administered orally once a day. This group will receive the placebo for 12 weeks.
|
|---|---|---|
|
Changes in GIS Scores Between Baseline and After a 12 Week Intervention With Mesalamine or Placebo
|
2.72 units on a scale
Standard Deviation 1.82 • Interval 4.52 to 5.14
|
2.22 units on a scale
Standard Deviation 1.49 • Interval 2.24 to 3.18
|
SECONDARY outcome
Timeframe: For 2 times: First time: at the time of patient recruitment in the study Second time: after the completion of first 12-week treatment period, all of which are during the time period from 02/25/2010 to 02/01/2012 (up to 2 years)Colonoscopy/flexible sigmoidoscopy will be performed and mucosal biopsies will be obtained. Each biopsy was stained for activated t lymphocytes, mast cells and eosinophils . CD117 staining was done for Mast cells. H and E staining was used to identify lymphocytes and eosinophils. Each path specimen was then noted to have increased versus normal number of these inflammatory cells.
Outcome measures
| Measure |
Mesalamine
n=7 Participants
This group received the drug Mesalamine for 12 weeks Mesalamine : Apriso is a 5-ASA drug with Intellicor ™ extended-release delivery technology. A 1.5 gram dosage of Apriso (equaling four 375 mg capsules) once a day will be administered orally for a period of 12 weeks
|
Placebo
n=6 Participants
This group will receive the Placebo for 12 weeks.
Placebo : 4 capsules (.375 gm sugar pill capsules) administered orally once a day. This group will receive the placebo for 12 weeks.
|
|---|---|---|
|
Number of Participants Who Had Evidence of Increased Levels of Pathologic Indicators of Colonic Mucosal Inflammation at 12 Weeks Compared to Baseline.
Increased Mast cells-CD 117 Positive staining
|
2 participants
|
2 participants
|
|
Number of Participants Who Had Evidence of Increased Levels of Pathologic Indicators of Colonic Mucosal Inflammation at 12 Weeks Compared to Baseline.
Increased eosinophil counts
|
3 participants
|
3 participants
|
|
Number of Participants Who Had Evidence of Increased Levels of Pathologic Indicators of Colonic Mucosal Inflammation at 12 Weeks Compared to Baseline.
Increased Activated T lymphocytes-CD3
|
2 participants
|
3 participants
|
SECONDARY outcome
Timeframe: An FBDSI score is administered at the beginning of each 12-week treatment period (baseline) and at the end of each 12-week treatment period.Population: Change in Functional Bowel Disorder Severity Index (FBDSI)after 12 weeks of intervention.
Subjects rate pain on a standardized scale. This is a standardized test used to evaluate patients with IBS. Baseline values are compared to 12 weeks after mesalamine and 12 weeks after placebo treatments. The FBDSI is score is interpreted as such: Severity of IBS is rated as none (0 points), mild (1-36 points), moderate as 37-110 points and severe as \>110 points. Therefore patients can have a score higher than 110.
Outcome measures
| Measure |
Mesalamine
n=7 Participants
This group received the drug Mesalamine for 12 weeks Mesalamine : Apriso is a 5-ASA drug with Intellicor ™ extended-release delivery technology. A 1.5 gram dosage of Apriso (equaling four 375 mg capsules) once a day will be administered orally for a period of 12 weeks
|
Placebo
n=6 Participants
This group will receive the Placebo for 12 weeks.
Placebo : 4 capsules (.375 gm sugar pill capsules) administered orally once a day. This group will receive the placebo for 12 weeks.
|
|---|---|---|
|
Functional Bowel Disorder Severity Index (FBDSI)
|
-14.5 units on a scale
Standard Deviation 61.5 • Interval 0.0 to 197.0
|
17 units on a scale
Standard Deviation 71 • Interval 0.0 to 209.0
|
SECONDARY outcome
Timeframe: at the time of recruitment and after completion of each 12-week treatment period, all of which are during the time period from 03/25/2010 to 02/01/2012 (up to 2 years)Population: Data are the mean change in IBS-QOL between baseline and intervention
A questionnaire is given to each patient and was completed at baseline then after 12 weeks of intervention with mesalamine and then placebo in the cross-over study. The IBS-QOL comprises 34 items with 5-point response scales (0 to 4) that cover eight dimensions of HRQL: dysphoria (8 items), interference with activity (7 items), body image (4 items), health worry (3 items),food avoidance (3 items), social reaction (4 items), sexual concerns (2 items) and relationships (3 items). Higher values indicate better HRQL after converting the raw score on the IBS-QOL into 0 to 100 points.
Outcome measures
| Measure |
Mesalamine
n=7 Participants
This group received the drug Mesalamine for 12 weeks Mesalamine : Apriso is a 5-ASA drug with Intellicor ™ extended-release delivery technology. A 1.5 gram dosage of Apriso (equaling four 375 mg capsules) once a day will be administered orally for a period of 12 weeks
|
Placebo
n=6 Participants
This group will receive the Placebo for 12 weeks.
Placebo : 4 capsules (.375 gm sugar pill capsules) administered orally once a day. This group will receive the placebo for 12 weeks.
|
|---|---|---|
|
IBS - Quality of Life (IBS-QOL)Score.
|
11 units on a scale
Standard Deviation 36.1 • Interval 40.0 to 163.0
|
-12.2 units on a scale
Standard Deviation 28.2 • Interval 38.0 to 124.0
|
SECONDARY outcome
Timeframe: at the time of recruitment and after completion of each 12-week treatment period, all of which are during the time period from 03/25/2010 to 02/01/2012 (up to 2 years)A questionnaire is given to each patient with scoring done on a Likert scale ranking from 0-42 which combines anxiety and depression scales. Each of these are scored from 0-21 depending on anxiety versus the depression parameters. Comparison of change in HADs after 12 weeks of intervention with either mesalamine or placebo is provided here with only the total value provided-range is from 0-42. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 3 with zero being none at all or occasional and 3 as most of the time. The scale used is a Likert scale and therefore the data returned from the HADS is ordinal. The best score for the HADS therefore is a 0 with the worst score a 42 for combined anxiety and depression scores. For the subscales of depression and anxiety, the best score is a 0 and the worst is a 21. This data is not provided here. Data below includes the change from baseline in the HADS scores.
Outcome measures
| Measure |
Mesalamine
n=7 Participants
This group received the drug Mesalamine for 12 weeks Mesalamine : Apriso is a 5-ASA drug with Intellicor ™ extended-release delivery technology. A 1.5 gram dosage of Apriso (equaling four 375 mg capsules) once a day will be administered orally for a period of 12 weeks
|
Placebo
n=6 Participants
This group will receive the Placebo for 12 weeks.
Placebo : 4 capsules (.375 gm sugar pill capsules) administered orally once a day. This group will receive the placebo for 12 weeks.
|
|---|---|---|
|
Hospital Anxiety and Depression Scale (HADS)
HADS score- change from baseline c/w 12 weeks
|
1.2 units on a scale
Standard Deviation 6.1
|
-2.4 units on a scale
Standard Deviation 8.7
|
|
Hospital Anxiety and Depression Scale (HADS)
HADS Score-end of 12 weeks
|
14 units on a scale
Standard Deviation 6.3
|
13 units on a scale
Standard Deviation 10.3
|
SECONDARY outcome
Timeframe: At the completion of each 12-week treatment period, all of which are during the time period from 03/25/2010 to 02/01/2012 (up to 2 years)Ability of test substances to permeate the intestinal mucosa. The Lactulose/Mannitol test (Genova Diagnostics®, Ashville, NC) directly measures the ability of mannitol and lactulose to permeate the intestinal mucosa. Patient ingests 5 grams of lactulose and 2 grams of mannitol dissolved in a 100 ml of water. Urine is then collected for 24 hours and the ratio of the urinary excretion of lactulose to mannitol is measured. This testing is performed only after completion of each treatment period , after 12 weeks of mesalamine and after 12 weeks of placebo. Normal ratio of lactulose/mannitol is any value \<0.7. An abnormal ratio is defined as \>0.7 ratio. The lactulose is measured in the urine as g/kg and the urinary excretion of mannitol is also measures as g/kg.
Outcome measures
| Measure |
Mesalamine
n=7 Participants
This group received the drug Mesalamine for 12 weeks Mesalamine : Apriso is a 5-ASA drug with Intellicor ™ extended-release delivery technology. A 1.5 gram dosage of Apriso (equaling four 375 mg capsules) once a day will be administered orally for a period of 12 weeks
|
Placebo
n=5 Participants
This group will receive the Placebo for 12 weeks.
Placebo : 4 capsules (.375 gm sugar pill capsules) administered orally once a day. This group will receive the placebo for 12 weeks.
|
|---|---|---|
|
Intestinal Permeability Testing
|
0.07 ratio
Interval 0.03 to 0.11
|
0.04 ratio
Interval 0.02 to 0.05
|
Adverse Events
Mesalamine Then Placebo
Placebo Then Mesalamine
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place