Colonic Polyps, Colon Cancer
Conditions
Keywords
Colon Cancer, Colonic Polyps, L-Menthol, C-Mint
Brief summary
The primary objective of this double-blinded, prospective, randomized placebo-controlled study is to evaluate for change in endoscopic adenoma detection rates (ADR) with the use of peppermint oil solution vs placebo application during colonoscopy. The investigators hypothesize that ADR will be increased with the use of the peppermint oil solution and thus further reduce the risk of colon cancer by means of colonoscopy.
Detailed description
Adult subjects who are undergoing colonoscopy for primary colorectal cancer screening or surveillance. The study will be carried out as a prospective, double-blinded, fully-masked randomized controlled trial. Prior to the trial entry, the participant's labs and medical record will be reviewed in the electronic records system. If the subject meets inclusion/exclusion criteria, he or she will be consented at bedside prior undergoing their scheduled procedure and receive standard care as otherwise. Experimental and placebo solution ingredients will be serially numbered and randomized in a 1:1 ratio using a variable block strategy and provided by the institutional investigational pharmacy. Research staff will draw up experimental or placebo solution in 4 syringes with a total of 20mL in each solution. The solutions are identical in appearance and endoscopic delivery. To prevent olfactory detection of the peppermint oil solution an essential oil diffuser will be used in all endoscopy rooms using the same oil as in the experimental solution. Endoscopists will be instructed to deliver the contents of one syringe sprayed via the endoscope in the cecum and one in the sigmoid colon. The contents of the other two syringes are to be delivered at the discretion of the endoscopist. After the procedure, endoscopists and study participants will be surveyed to determine if blinding was effective and to assess patient comfort levels, respectively. The primary and secondary end points will be determined on an intention to treat basis.
Interventions
DRUGPeppermint Oil
During the colonoscopy the Endoscopists will be required to deliver intraluminally 1 syringe at the cecum and 1 syringe in the sigmoid colon. Up to 2 additional doses can be delivered at the discretion of the endoscopist up to a maximum of 4 total doses (max total dose = 640 mg of L-Menthol).
OTHERPlacebo
During the colonoscopy the Endoscopists will be required to deliver intraluminally 1 syringe at the cecum and 1 syringe in the sigmoid colon. Up to 2 additional doses can be delivered at the discretion of the endoscopist up to a maximum of 4 total doses (max total dose = 80 ml of Solution B, also has 0 mg of L-Menthol).
Sponsors
University Hospitals Cleveland Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. At least 50 years of age in Caucasians or 45 years of age in African-Americans. 2. Patients undergoing primary screening colonoscopy (either average risk or increased-risk) or surveillance colonoscopy after prior screening/surveillance colonoscopy. 3. Capable of understanding instructions, adhering to study schedules and requirements, and willing to provide informed consent.
Exclusion criteria
1. History of colectomy, partial or complete 2. Symptoms suggesting possible colorectal stenosis or cancer 3. Inflammatory bowel disease 4. Familial polyposis syndromes 5. History of, or current diagnosis of colorectal cancer 6. American Society of Anesthesia Physical Stats (ASA PS) score of IV or greater 7. Non-correctable coagulopathy 8. Currently receiving anti-thrombotic therapy, with an INR \> 1.5 9. Poor prep, total BBPS score \< 6, or any part of the colon \< 2. 10. Patients with known allergy to peppermint oil or peppermint containing products. 11. Patients taking calcium channel blockers (Amlodipine, Nifedipine, Verapamil, Diltiazem, Dihydropyridine, Felodipine, etc).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adenoma Detection Rates | 2 weeks | Evaluate for changes in adenoma detection rates with the use of intraluminal peppermint oil application vs sterile water application during colonoscopy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Polyp Detection Rates | 1 week . | Evaluate for changes in Polyp detection rates. |
| Procedure Time | immediate | Evaluate for changes in total procedure time, cecal intubation time, and withdrawal time with the use of intraluminal peppermint oil application vs sterile water application during colonoscopy. |
| Advanced Adenoma Detection Rates | 2 weeks | Evaluate for changes in advanced adenoma detection rates with the use of intraluminal peppermint oil application vs placebo during coloscopy. Advanced adenoma will be define as an adenoma with significant villous features (\>25%), size of 1.0 cm or more, high-grade dysplasia, or early invasive cancer. |
| Cancer Detection Rates | 2 weeks | Evaluate for changes in cancer detection rates with the use of intraluminal peppermint oil application vs placebo during colonoscopy. |
| Patient Comfort Level Recorded on Post-procedure Survey | 1 day | Evaluate for changes in reported patient comfort levels with the use of intraluminal peppermint oil application vs placebo during colonoscopy. |
Countries
United States
Participant flow
Recruitment details
Day1 - patients undergoing screening and surveillance colonoscopy are pre-screened to evaluate if they meet inclusion criteria. Once identified patient is approached by study personnel to determine their willingness. If willing to participate will undergo written consent for participation. Patients will be followed up by telephone for adverse reactions at 24-48 hr, one week and one month after colonoscopy.
Pre-assignment details
Patients will be questioned regarding their allergy status specific to peppermint oil and this will be documented in the consent form and in the RedCap database. The patient must meet all inclusion and exclusion criteria and willing to participate in informed consent.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Solution B) Placebo solution
Ingredients:
1. 0.4mL of Tween® 80 (i.e. Polysorbate 80) - this is a commonly used food additive that acts as a surfactant to bring the peppermint oil into solution
2. 1L prepackage sterile water
3. 2.6mL of undyed simethicone
Instructions to prepare:
4. Add tween and simethicone to sterile water. Then, shake vigorously.
5. Once solution has settled, and patient has been randomized, draw 20mL of solution into a plastic syringe
Placebo: During the colonoscopy the Endoscopists will be required to deliver intraluminally 1 syringe at the cecum and 1 syringe in the sigmoid colon. Up to 2 additional doses can be delivered at the discretion of the endoscopist up to a maximum of 4 total doses (max total dose = 80 ml of Solution B ; with 0 mg of L-Methol). | 38 |
| Peppermint Oil Solution A) Peppermint oil solution (1.6% peppermint oil, which is 0.8% L-menthol)
Ingredients:
1. 16mL of peppermint oil (provided by the NowFoods® company)
2. 0.4mL of Tween® 80 (i.e. Polysorbate 80) - this is a commonly used food additive that acts as a surfactant to bring the peppermint oil into solution
3. 1L prepackage sterile water
4. 2.6mL of undyed simethicone
Peppermint Oil: During the colonoscopy the Endoscopists will be required to deliver intraluminally 1 syringe at the cecum and 1 syringe in the sigmoid colon. Up to 2 additional doses can be delivered at the discretion of the endoscopist up to a maximum of 4 total doses (max total dose = 640mg L-Menthol). | 37 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 4 | 3 |
Baseline characteristics
| Characteristic | Peppermint Oil | Total | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 17 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 58 Participants | 28 Participants |
| Age, Continuous | 67.73 years STANDARD_DEVIATION 8.8 | 60.5 years STANDARD_DEVIATION 7.77 | 60.5 years STANDARD_DEVIATION 6.75 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 37 Participants | 75 Participants | 38 Participants |
| Sex: Female, Male Female | 25 Participants | 46 Participants | 21 Participants |
| Sex: Female, Male Male | 12 Participants | 29 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 37 | 0 / 38 |
| other Total, other adverse events | 7 / 37 | 8 / 38 |
| serious Total, serious adverse events | 0 / 37 | 0 / 38 |
Outcome results
Primary
Adenoma Detection Rates
Evaluate for changes in adenoma detection rates with the use of intraluminal peppermint oil application vs sterile water application during colonoscopy.
Time frame: 2 weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Peppermint Oil | Adenoma Detection Rates | Adenoma Detected Yes Yes Adenoma Detected | 19 Participants |
| Peppermint Oil | Adenoma Detection Rates | Adenoma Detected No | 18 Participants |
| Placebo | Adenoma Detection Rates | Adenoma Detected Yes Yes Adenoma Detected | 20 Participants |
| Placebo | Adenoma Detection Rates | Adenoma Detected No | 18 Participants |
Secondary
Advanced Adenoma Detection Rates
Evaluate for changes in advanced adenoma detection rates with the use of intraluminal peppermint oil application vs placebo during coloscopy. Advanced adenoma will be define as an adenoma with significant villous features (\>25%), size of 1.0 cm or more, high-grade dysplasia, or early invasive cancer.
Time frame: 2 weeks
Population: The data was not entered in the database in a format that would allow it to be collated according to the definition above. Also, some subjects did show more than one advanced adenoma.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peppermint Oil | Advanced Adenoma Detection Rates | Tubular Adenoma | 19 participants |
| Peppermint Oil | Advanced Adenoma Detection Rates | Tubulovillous Adenoma | 0 participants |
| Peppermint Oil | Advanced Adenoma Detection Rates | Villous Adenoma | 0 participants |
| Peppermint Oil | Advanced Adenoma Detection Rates | Serrated Adenoma | 1 participants |
| Peppermint Oil | Advanced Adenoma Detection Rates | Cancer | 1 participants |
| Peppermint Oil | Advanced Adenoma Detection Rates | No Adenoma | 18 participants |
| Placebo | Advanced Adenoma Detection Rates | Cancer | 1 participants |
| Placebo | Advanced Adenoma Detection Rates | Tubular Adenoma | 19 participants |
| Placebo | Advanced Adenoma Detection Rates | Serrated Adenoma | 4 participants |
| Placebo | Advanced Adenoma Detection Rates | Tubulovillous Adenoma | 0 participants |
| Placebo | Advanced Adenoma Detection Rates | No Adenoma | 18 participants |
| Placebo | Advanced Adenoma Detection Rates | Villous Adenoma | 0 participants |
Secondary
Cancer Detection Rates
Evaluate for changes in cancer detection rates with the use of intraluminal peppermint oil application vs placebo during colonoscopy.
Time frame: 2 weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Peppermint Oil | Cancer Detection Rates | Cancer detected Yes | 1 Participants |
| Peppermint Oil | Cancer Detection Rates | Cancer detected No | 36 Participants |
| Placebo | Cancer Detection Rates | Cancer detected No | 37 Participants |
| Placebo | Cancer Detection Rates | Cancer detected Yes | 1 Participants |
Secondary
Patient Comfort Level Recorded on Post-procedure Survey
Evaluate for changes in reported patient comfort levels with the use of intraluminal peppermint oil application vs placebo during colonoscopy.
Time frame: 1 day
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Peppermint Oil | Patient Comfort Level Recorded on Post-procedure Survey | Slight Discomfort | 15 Participants |
| Peppermint Oil | Patient Comfort Level Recorded on Post-procedure Survey | Severe | 0 Participants |
| Peppermint Oil | Patient Comfort Level Recorded on Post-procedure Survey | Moderate(bothersome) | 5 Participants |
| Peppermint Oil | Patient Comfort Level Recorded on Post-procedure Survey | Not available | 0 Participants |
| Peppermint Oil | Patient Comfort Level Recorded on Post-procedure Survey | No Discomfort | 17 Participants |
| Placebo | Patient Comfort Level Recorded on Post-procedure Survey | Not available | 3 Participants |
| Placebo | Patient Comfort Level Recorded on Post-procedure Survey | No Discomfort | 19 Participants |
| Placebo | Patient Comfort Level Recorded on Post-procedure Survey | Slight Discomfort | 15 Participants |
| Placebo | Patient Comfort Level Recorded on Post-procedure Survey | Moderate(bothersome) | 1 Participants |
| Placebo | Patient Comfort Level Recorded on Post-procedure Survey | Severe | 0 Participants |
Secondary
Polyp Detection Rates
Evaluate for changes in Polyp detection rates.
Time frame: 1 week .
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Peppermint Oil | Polyp Detection Rates | Polyp detected Yes | 30 Participants |
| Peppermint Oil | Polyp Detection Rates | Polyp detected No | 7 Participants |
| Placebo | Polyp Detection Rates | Polyp detected Yes | 29 Participants |
| Placebo | Polyp Detection Rates | Polyp detected No | 9 Participants |
Secondary
Procedure Time
Evaluate for changes in total procedure time, cecal intubation time, and withdrawal time with the use of intraluminal peppermint oil application vs sterile water application during colonoscopy.
Time frame: immediate
Population: Note that total procedure time was not collected
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Peppermint Oil | Procedure Time | Cecal Intubation time in minutes | 12.4 minutes |
| Peppermint Oil | Procedure Time | Withdraw Time in minutes | 20.5 minutes |
| Placebo | Procedure Time | Cecal Intubation time in minutes | 12.9 minutes |
| Placebo | Procedure Time | Withdraw Time in minutes | 17.2 minutes |