Colorectal Cancer
Conditions
Brief summary
Single Centre, open label assignment phase II clinical study. To evaluate the effect of oral 200mg Methylene Blue tablets (administered 8x25mg) prior to endoscopy on double stranded DNA breaks in colonic biopsy samples assessed by histone gamma H2AX analysis, compared to control biopsies.
Detailed description
Primary Objective: To evaluate the effect of oral 200 mg Methylene Blue MMX® tablets, (administered as 8 x 25 mg), prior to endoscopy, on double-stranded DNA breaks in colonic biopsy samples assessed by histone γH2AX analysis, compared to control biopsies collected during standard white light colonoscopy without the prior use of Methylene Blue MMX®. Secondary Objectives : To evaluate the safety and tolerability of oral Methylene Blue MMX® tablets.. To evaluate the staining score for colonoscopy obtained with oral Methylene Blue MMX® tablets . Time to reach the caecum during colonoscopy and withdrawal time from caecum to exit.
Interventions
PROCEDUREstandard white light colonoscopy-equivalent to placebo
standard white light colonoscopy
DRUGMethylene Blue MMX tablets
8x25mg methylene blue MMX tablets administered before a colonoscopy
Sponsors
Cosmo Technologies Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Males or females, aged between 18 and 75. * Outpatients scheduled for screening or surveillance colonoscopy * Subjects must be identified as having the clinical requirement for second colonoscopy within 2weeks of the initial colonoscopy. * Women of childbearing potential must use at least one reliable method of contraception, be surgically sterilised or be abstinent. * For female subjects, a negative serum pregnancy test is required before Methylene Blue MMX® tablets are dispensed to the subject. * Post menopausal patients need to have a period of greater than 1year since last menstrual period. * Subjects must be able to comprehend the full nature and purpose of the study, including possible risks and side effects. * Subjects must be able to co-operate with the investigator and to comply with the requirements of the entire study. * Signed written informed consent prior to inclusion in the study.
Exclusion criteria
* No Pregnant or lactating women, or women undergoing fertility treatment. * No previous medical history of, or suspected hypersensitivity to the Methylene Blue and/or this formulations ingredients. * No previous medical history of, or suspected hypersensitivity to the PEG based bowel cleansing preparation and/or this formulations ingredients. * No previous medical history of gastrointestinal obstruction or perforation, toxic megacolon, major colonic resection, severe diverticulitis, heart failure (Class III or IV), serious cardiovascular disease. * No ALT, AST, GGT, Bilirubin, Creatinine or Urea greater than 2.5 x the upper limit for normal, based on local laboratory testing. * No clinical alarm symptoms or history of anaemia (previously recorded haemoglobin of less than 10mg/dL) or frank blood in the stool within the last 30 days prior to enrolment. * No known deficiency of glucose-6-phosphate dehydrogenase. * No known deficiency of NADPH reductase. * No treatment within 5 weeks prior to randomisation with Fluoxetine (Prozac). * No concurrent treatment, or previous treatment within 2 weeks with any of the prohibited psychiatric medications that may interact with Methylene Blue as listed in the Prohibited Medications section; Selective Serotonin Reuptake Inhibitors (SSRI), Serotonin-Norepinepherine Reuptake Inhibitors (SNRI's), listed Tricyclic anti-depressants or Monoamine oxidase A inhibitors. * No concurrent treatment with anticoagulants, or antiaggregants, inducing an INR \> 1.5. * No current enrolment in any other clinical trial, or previous enrolment in a clinical trial within the last 30 days. * No other medical condition that in the investigators opinion would make the administration of the study drug or procedures hazardous to the subject.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gamma H2AX Histone Levels in Colonic Biopsy During Standard White Light Colonoscopy and Colonoscopy for Which Methylene Blue MMX Was Taken Prior to Initiating the Colonoscopy | 2 weeks | Assay of gamma H2AX histone phosphorylation in biopsy samples collected during colonoscopy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Evaluate the Staining Quality Obtained With Oral Methylene Blue MMX® Tablets. | During the colonoscopy | Staining quality (SC) observed in each colonic region, in the FAS set (N=10); mean (±SD) is reported for SC. SC is ranked as follows: 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) |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MB MMX 200mg Subjects who have had samples collected during initial colonoscopy, who require a second colonoscopy within 2 weeks. Prior to this second colonoscopy the subjects take Methylene Blue MMX tablets. Biopsies collected are compared to their initial colonoscopy for histone gamma H2AX activity.
Methylene Blue MMX tablets: 8x25mg methylene blue MMX tablets administered before a colonoscopy.
Subjects were counted as part of an analysis group once they had received the IMP. The discontinued subjects in this study we discontinued before received the IMP. | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | MB MMX 200mg |
|---|---|
| Age, Continuous | 63.1 Years STANDARD_DEVIATION 9.2 |
| Body weight | 74.40 kg STANDARD_DEVIATION 15.48 |
| Height | 168.2 cm STANDARD_DEVIATION 11.2 |
| Region of Enrollment Italy | 10 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 13 |
| other Total, other adverse events | 8 / 13 |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
Primary
Gamma H2AX Histone Levels in Colonic Biopsy During Standard White Light Colonoscopy and Colonoscopy for Which Methylene Blue MMX Was Taken Prior to Initiating the Colonoscopy
Assay of gamma H2AX histone phosphorylation in biopsy samples collected during colonoscopy.
Time frame: 2 weeks
Population: FAS = 10
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MB MMX 200mg | Gamma H2AX Histone Levels in Colonic Biopsy During Standard White Light Colonoscopy and Colonoscopy for Which Methylene Blue MMX Was Taken Prior to Initiating the Colonoscopy | 0 subject biopsies that tested + for γH2AX |
Comparison: The results of the γH2AX analysis were listed and summarised by frequency tables by visit and colonic region.~The results were compared between Visit 2 and Visit 1 for each colonic region and overall using the Mc Nemar's χ2 test.~In case of the presence of at least one positive colonic region, that visit was to be considered as 'Positive' for the overall γH2AX analysis.
Secondary
To Evaluate the Staining Quality Obtained With Oral Methylene Blue MMX® Tablets.
Staining quality (SC) observed in each colonic region, in the FAS set (N=10); mean (±SD) is reported for SC. SC is ranked as follows: 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 the colonoscopy
Population: Full Analysis Set (FAS): all included subjects, who received at least one dose of the IMP and had at least one biopsy for the evaluation of the level of γH2AX post-enrolment. This analysis set was used for the primary analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MB MMX 200mg | To Evaluate the Staining Quality Obtained With Oral Methylene Blue MMX® Tablets. | Ascending colon | 2.9 Units on a 6 point scale | Standard Deviation 1.3 |
| MB MMX 200mg | To Evaluate the Staining Quality Obtained With Oral Methylene Blue MMX® Tablets. | Transverse colon | 3.2 Units on a 6 point scale | Standard Deviation 0.8 |
| MB MMX 200mg | To Evaluate the Staining Quality Obtained With Oral Methylene Blue MMX® Tablets. | Descending colon | 2.7 Units on a 6 point scale | Standard Deviation 1.2 |
| MB MMX 200mg | To Evaluate the Staining Quality Obtained With Oral Methylene Blue MMX® Tablets. | Rectosigmoid | 2.2 Units on a 6 point scale | Standard Deviation 1.6 |