Ulcerative Colitis
Conditions
Brief summary
Evaluation of the intraepithelial neoplasia detection rate in patients with long standing ulcerative colitis undergoing mucosal staining with oral methylene blue MMX tablets prior to colonoscopy.
Interventions
DEVICEoral delivery mucosal stain
200mg methylene blue MMX tablet taken prior to colonoscopy
Sponsors
Cosmo Technologies Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* endoscopically verified UC signed written informed consent
Exclusion criteria
* Known or suspected GI obstruction or perforation Liver or renal impairment, malignancy, pregnancy or lactation, suppressed PT.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intraepithelial Neoplasia (IN) Detection Rate (False Negative Findings) | During colonscopy (usually <15 min) and subsequent histological analysis | The rate of intraepithelial neoplasiae detection in the whole colon is summarised along with the number and percentage of subjects affected. The number and percentage of false and true negative and of false and true positive findings of intraepithelial neoplasiae are also listed. |
| Intraepithelial Neoplasia (IN) Detection Rate (True Positive Findings) | During colonscopy (usually <15 min) and subsequent histological analysis | The rate of intraepithelial neoplasiae detection in the whole colon is summarised along with the number and percentage of subjects affected. The number and percentage of false and true negative and of false and true positive findings of intraepithelial neoplasiae are also listed. |
| Intraepithelial Neoplasia (IN) Detection Rate (False Positive Findings) | During colonscopy (usually <15 min) and subsequent histological analysis | The rate of intraepithelial neoplasiae detection in the whole colon is summarised along with the number and percentage of subjects affected. The number and percentage of false and true negative and of false and true positive findings of intraepithelial neoplasiae are also listed. |
| Intraepithelial Neoplasia (IN) Detection Rate (True Negative Findings) | During colonscopy (usually <15 min) and subsequent histological analysis | The rate of intraepithelial neoplasiae detection in the whole colon is summarised along with the number and percentage of subjects affected. The number and percentage of false and true negative and of false and true positive findings of intraepithelial neoplasiae are also listed. |
| Detected Intraepithelial Neoplasia | During colonscopy (usually <15 min) and subsequent histological analysis | Rate of intraepithelial neoplasiae detection in the whole colon. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Mucosal Staining Efficacy of Methylene Blue MMX® Tablets After a Total Oral Dose of 200 mg Administered During and at the End of the Intake of the Bowel Cleansing Preparation. | During colonscopy (usually <15 min) and subsequent histological analysis | The mucosal staining efficacy of Methylene Blue MMX® tablets was assessed in all 4 examined colonic regions (ascending, transverse and descending colon and rectosigmoid). The staining efficacy in each colon region was assessed scoring the observed staining percentage as reported below: 0\. no staining 1. traces (poor traces in colon mucosa) 2. detectable (at least the 25% of colon mucosa is stained) 3. acceptable (at least the 50% of colon mucosa is stained) 4. good (at least the 75% of colon mucosa is stained) 5. overstained (the 100% of the colon mucosa is over stained) |
| Bowel Cleansing Quality Evaluated by Boston Bowel Preparation Scale After Intake of Bowel Cleansing Formulation and of a Total Dose of 200 mg of Methylene Blue MMX Tablets Administered During and at the End of the Intake of the Bowel Cleansing Formulation | During colonscopy (usually <15 min) | The Boston Bowel Preparation Score (BBPS) was used to rate colon cleansing quality. Each of the following 3 regions was rated: right, mid and rectosigmoid colon. The following 4-point scale (0-3) was used. 0 - unprepared colon segment with mucosa not seen due to solid stool that cannot be cleared 1. \- portion of mucosa of the colon segment seen, but other areas of the colon segment not well seen due to staining, residual stool and/or opaque liquid 2. \- minor amount of residual staining, small fragments of stool and/or opaque liquid, but mucosa of colon segment seen well 3. \- entire mucosa of colon segment seen well with no residual staining, small fragments of stool or opaque liquid. Each region of the colon received a segment score from 0 to 3 and these segment scores were summed for a total BBPS score ranging from 0 to 9. Therefore, the maximum BBPS score for a perfectly clean colon, without any residual liquid, is 9 and the minimum BBPS score for an unprepared colon is 0. |
| The Extent and Severity of the Inflamed Mucosa | During colonscopy (usually <15 min) and subsequent histological analysis | The inflammation conditions of the mucosa were evaluated during the colonoscopy and, afterwards, in the bioptic specimens. Rachmilewitz EI and Saverymuttu scores were used to assess inflammation. Rachmilewitz's scoring system for endoscopic index (EI) measures granulation scattering reflected light, vascular pattern, vulnerability of mucose and mucosal damage on a scoring scale of 0 to 4 from normal to damaged. Saverymuttu's scoring system for enteric specimens assesses disease activity in the bowel by rating histological changes in enterocytes, crypts, lamina propria mononuclear cells and lamina propria neutrophils. The average score for histological changes in individual biopsy specimens was summed and converted into a grade from 1 to 4, increasing in severity. |
Countries
Italy
Participant flow
Recruitment details
This study recruited patients with a diagnosis of ulcerative colitis dating not less than 8 years.
Pre-assignment details
This was an exploratory, non-comparative study with no randomization. All subjects were allocated to receive Selg 1000® 4 L bowel preparation, the day before colonoscopy. All study subjects were allocated to receive 200 mg of Methylene Blue MMX® tablets during and at the end of the intake of bowel cleansing preparation.
Participants by arm
| Arm | Count |
|---|---|
| Patients With UC Undergoing Colonoscopy oral delivery mucosal stain: 200mg methylene blue MMX tablet taken prior to colonoscopy | 52 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Subject discontinued (moderate illness) | 1 |
Baseline characteristics
| Characteristic | Patients With UC Undergoing Colonoscopy | — |
|---|---|---|
| Age, Continuous Age | 45.9 Years STANDARD_DEVIATION 9.7 | — |
| Body weight | 70.04 kg STANDARD_DEVIATION 9.57 | — |
| Height | 168.9 cm STANDARD_DEVIATION 8.4 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 22 Participants | — |
| Sex: Female, Male Male | 30 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 53 |
| other Total, other adverse events | 8 / 53 |
| serious Total, serious adverse events | 0 / 53 |
Outcome results
Primary
Detected Intraepithelial Neoplasia
Rate of intraepithelial neoplasiae detection in the whole colon.
Time frame: During colonscopy (usually <15 min) and subsequent histological analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Full Analysis Set (FAS) | Detected Intraepithelial Neoplasia | 0.2 Number of detected IN | Standard Deviation 0.5 |
Comparison: The number of detected neoplasiae for each patient was listed and summarised by descriptive statistics. Number and percentage of patients with intraepithelial neoplasiae was presented
Primary
Intraepithelial Neoplasia (IN) Detection Rate (False Negative Findings)
The rate of intraepithelial neoplasiae detection in the whole colon is summarised along with the number and percentage of subjects affected. The number and percentage of false and true negative and of false and true positive findings of intraepithelial neoplasiae are also listed.
Time frame: During colonscopy (usually <15 min) and subsequent histological analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Full Analysis Set (FAS) | Intraepithelial Neoplasia (IN) Detection Rate (False Negative Findings) | 5.8 percentage of false neg. findings of IN |
Primary
Intraepithelial Neoplasia (IN) Detection Rate (False Positive Findings)
The rate of intraepithelial neoplasiae detection in the whole colon is summarised along with the number and percentage of subjects affected. The number and percentage of false and true negative and of false and true positive findings of intraepithelial neoplasiae are also listed.
Time frame: During colonscopy (usually <15 min) and subsequent histological analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Full Analysis Set (FAS) | Intraepithelial Neoplasia (IN) Detection Rate (False Positive Findings) | 7.7 percentage of false pos. findings of IN |
Primary
Intraepithelial Neoplasia (IN) Detection Rate (True Negative Findings)
The rate of intraepithelial neoplasiae detection in the whole colon is summarised along with the number and percentage of subjects affected. The number and percentage of false and true negative and of false and true positive findings of intraepithelial neoplasiae are also listed.
Time frame: During colonscopy (usually <15 min) and subsequent histological analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Full Analysis Set (FAS) | Intraepithelial Neoplasia (IN) Detection Rate (True Negative Findings) | 78.8 percentage of true neg. findings of IN |
Primary
Intraepithelial Neoplasia (IN) Detection Rate (True Positive Findings)
The rate of intraepithelial neoplasiae detection in the whole colon is summarised along with the number and percentage of subjects affected. The number and percentage of false and true negative and of false and true positive findings of intraepithelial neoplasiae are also listed.
Time frame: During colonscopy (usually <15 min) and subsequent histological analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Full Analysis Set (FAS) | Intraepithelial Neoplasia (IN) Detection Rate (True Positive Findings) | 7.7 percentage of true pos. findings of IN |
Secondary
Bowel Cleansing Quality Evaluated by Boston Bowel Preparation Scale After Intake of Bowel Cleansing Formulation and of a Total Dose of 200 mg of Methylene Blue MMX Tablets Administered During and at the End of the Intake of the Bowel Cleansing Formulation
The Boston Bowel Preparation Score (BBPS) was used to rate colon cleansing quality. Each of the following 3 regions was rated: right, mid and rectosigmoid colon. The following 4-point scale (0-3) was used. 0 - unprepared colon segment with mucosa not seen due to solid stool that cannot be cleared 1. \- portion of mucosa of the colon segment seen, but other areas of the colon segment not well seen due to staining, residual stool and/or opaque liquid 2. \- minor amount of residual staining, small fragments of stool and/or opaque liquid, but mucosa of colon segment seen well 3. \- entire mucosa of colon segment seen well with no residual staining, small fragments of stool or opaque liquid. Each region of the colon received a segment score from 0 to 3 and these segment scores were summed for a total BBPS score ranging from 0 to 9. Therefore, the maximum BBPS score for a perfectly clean colon, without any residual liquid, is 9 and the minimum BBPS score for an unprepared colon is 0.
Time frame: During colonscopy (usually <15 min)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Full Analysis Set (FAS) | Bowel Cleansing Quality Evaluated by Boston Bowel Preparation Scale After Intake of Bowel Cleansing Formulation and of a Total Dose of 200 mg of Methylene Blue MMX Tablets Administered During and at the End of the Intake of the Bowel Cleansing Formulation | Right colon | 1.3 Boston bowel preparation scale (BBPS) | Standard Deviation 0.5 |
| Full Analysis Set (FAS) | Bowel Cleansing Quality Evaluated by Boston Bowel Preparation Scale After Intake of Bowel Cleansing Formulation and of a Total Dose of 200 mg of Methylene Blue MMX Tablets Administered During and at the End of the Intake of the Bowel Cleansing Formulation | Mid colon | 1.7 Boston bowel preparation scale (BBPS) | Standard Deviation 0.5 |
| Full Analysis Set (FAS) | Bowel Cleansing Quality Evaluated by Boston Bowel Preparation Scale After Intake of Bowel Cleansing Formulation and of a Total Dose of 200 mg of Methylene Blue MMX Tablets Administered During and at the End of the Intake of the Bowel Cleansing Formulation | Rectosigmoid colon | 1.7 Boston bowel preparation scale (BBPS) | Standard Deviation 0.5 |
Secondary
The Extent and Severity of the Inflamed Mucosa
The inflammation conditions of the mucosa were evaluated during the colonoscopy and, afterwards, in the bioptic specimens. Rachmilewitz EI and Saverymuttu scores were used to assess inflammation. Rachmilewitz's scoring system for endoscopic index (EI) measures granulation scattering reflected light, vascular pattern, vulnerability of mucose and mucosal damage on a scoring scale of 0 to 4 from normal to damaged. Saverymuttu's scoring system for enteric specimens assesses disease activity in the bowel by rating histological changes in enterocytes, crypts, lamina propria mononuclear cells and lamina propria neutrophils. The average score for histological changes in individual biopsy specimens was summed and converted into a grade from 1 to 4, increasing in severity.
Time frame: During colonscopy (usually <15 min) and subsequent histological analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Full Analysis Set (FAS) | The Extent and Severity of the Inflamed Mucosa | Rachmilewitz EI | 2.1 Rachmilewitz and Saverymuttu scores | Standard Deviation 3 |
| Full Analysis Set (FAS) | The Extent and Severity of the Inflamed Mucosa | Saverymuttu grade | 1.1 Rachmilewitz and Saverymuttu scores | Standard Deviation 1 |
Secondary
The Mucosal Staining Efficacy of Methylene Blue MMX® Tablets After a Total Oral Dose of 200 mg Administered During and at the End of the Intake of the Bowel Cleansing Preparation.
The mucosal staining efficacy of Methylene Blue MMX® tablets was assessed in all 4 examined colonic regions (ascending, transverse and descending colon and rectosigmoid). The staining efficacy in each colon region was assessed scoring the observed staining percentage as reported below: 0\. no staining 1. traces (poor traces in colon mucosa) 2. detectable (at least the 25% of colon mucosa is stained) 3. acceptable (at least the 50% of colon mucosa is stained) 4. good (at least the 75% of colon mucosa is stained) 5. overstained (the 100% of the colon mucosa is over stained)
Time frame: During colonscopy (usually <15 min) and subsequent histological analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Full Analysis Set (FAS) | The Mucosal Staining Efficacy of Methylene Blue MMX® Tablets After a Total Oral Dose of 200 mg Administered During and at the End of the Intake of the Bowel Cleansing Preparation. | Ascending colon | 3.4 Staining score | Standard Deviation 1 |
| Full Analysis Set (FAS) | The Mucosal Staining Efficacy of Methylene Blue MMX® Tablets After a Total Oral Dose of 200 mg Administered During and at the End of the Intake of the Bowel Cleansing Preparation. | Transverse colon | 3.0 Staining score | Standard Deviation 0.9 |
| Full Analysis Set (FAS) | The Mucosal Staining Efficacy of Methylene Blue MMX® Tablets After a Total Oral Dose of 200 mg Administered During and at the End of the Intake of the Bowel Cleansing Preparation. | Descending colon | 2.9 Staining score | Standard Deviation 1.1 |
| Full Analysis Set (FAS) | The Mucosal Staining Efficacy of Methylene Blue MMX® Tablets After a Total Oral Dose of 200 mg Administered During and at the End of the Intake of the Bowel Cleansing Preparation. | Rectosigmoid | 2.8 Staining score | Standard Deviation 1.1 |