Effect of Oral Administration of Methylene Blue MMX Tablets on Double Stranded DNA

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effect of Oral Administration of Methylene Blue MMX Tablets on Double-stranded DNA Damage Assessed by GammaH2AX Analysis of Colon Biopsy Samples

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Procedure: standard white light colonoscopy-equivalent to placebo
* Drug: Methylene Blue MMX tablets


Participation Criteria
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Eligibility Criteria
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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. Exclusion Criteria: -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group A<br>Biopsy samples collected during standard white light colonoscopy. | Procedure: standard white light colonoscopy-equivalent to placebo<br>* standard white light colonoscopy<br>|
| Active Comparator: Group B<br>Subjects who have had samples collected during a Group A 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 previous group A colonoscopy for histone gamma H2AX activity. | Drug: Methylene Blue MMX tablets<br>* 8x25mg methylene blue MMX tablets administered before a colonoscopy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 traces (poor traces in colon mucosa) detectable (at least the 25% of colon mucosa is stained) acceptable (at least the 50% of colon mucosa is stained) good (at least the 75% of colon mucosa is stained) overstained ( the 100% of the colon mucosa is over stained) | During the colonoscopy |