start date: April 2017
estimated completion: April 2018
last updated: February 23, 2017
phase of development: Phase 2
size / enrollment: 40
study design: Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
6 months of Curcumin vs. placebo treatment outcomes will be compared.
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Masking Description:
Placebo and curcumin capsules are identical in appearance, and will be marked as "A" or "B". Study participants and staff will be blinded to the capsule content. A locked file containing the description will remain in a locked file on the study coordinators computer.
Primary Purpose: Treatment
study description: Fourty individuals with identified APC mutation or MUTYH mutation that result in a phenotype of multiple colonic adenomas with or without duodenal adenomas will be included in the study. Participants will be allocated in a 1:1 ratio to receive either wholistic Turmeric capsules (Pukka herbs) or placebo for 6 months.
Participants will be assessed by a gastroenterologist 4-8 weeks after initiation, and at termination/conclusion visit at 6 months.
Blood, stool and urine samples will be collected at baseline, after 4-8 weeks and at 6 months just before final colonoscopy.
Serum samples will be used for testing complete blood count, liver function test, C-reactive protein (CRP) Various cytokines and small molecule measurements. Stool samples will be evaluated for microbiome composition.
Curcumin and curcuminoid levels will be measured in tissue serum, stool and urine will be measured in a subsample of patients.
Colonoscopy will be performed at study entry with removal of all polyps larger than 20mm, count and precise size measurement of polyps by a standard forceps, throughout the colon and in defined segments. Retained polyps will be counted and measured with an open forceps placed near the polyp to determine size. A full video and photos of the procedure will be taken. In cases with multiple polyps that cannot be counted or properly evaluated the PI will decide if a defined area like the rectum could be evaluated and will define it in terms of distance from the anus. In this case the video of the procedure will be evaluated by two separate gastroeneterologists blinded to treatment arm.
Frozen samples from normal mucosa will be taken at study entry. Samples from polyps will be taken preferably in cases with multiple polyp in order not to interrupt measurments.
Upper endoscopy only in patients with known duodenal adenomas will also be performed at study entry with as above evaluation. Sample from polyps and normal mucosa will be taken as above. A full video and photos of the upper endoscopy will be recorded as well.
A 2nd colonoscopy +/- gastroscopy will be performed at 6 months when all polyps will be counted and pictured by video and photography. Size determination in a similar way as above, throughout the colon or in the defined area as was decided at baseline colonoscopy.
Frozen samples from polyps and normal mucosa will be taken and polypoectomy will be performed upon the decision of the endoscopist in both lower and upper endoscopies.
Frozen tissue specimen will be used for H&E, various proliferation and apoptosis staining like KI67.
Tissue, blood, urine and stool samples will be frozen and sent for analysis.
Inclusion/screening visit will include:
-Intake of patient medical history.
-Exact documentation of identified genetic mutation per genetic consultation.
-Case report form (CRF).
-Blood test including complete blood count, liver function test, C-reactive protein (CRP) and sera for subsequent cytokine analysis.
-Urine and Stool collection .
-Basline colonoscopy and/or upper endoscopy as detiled above with tissue collection and tattoo of tissue sampled.
Mid-term visit at 4-8 weeks will include:
-Case report form (CRF).
-Collection of Blood, urine and stool specimens.
Termination/conclusion visit will include:
-Case report form (CRF).
-Collection of blood, urine, stool specimens.
-Colonoscopy and upper endoscopy as described above with tissue collection of same tissue identified by tattoo.
primary outcomes:
- Number of polyps [ Time Frame: 6 months ]
- Size of polyps [ Time Frame: 6 months ]
secondary outcomes:
- Histological apoptosis assays in frozen polyps and normal tissue (such as KI67, caspase 3 activity and COX-2 expression). [ Time Frame: 6 months ]
- Histological proliferation assays in frozen polyps and normal tissue (such as KI67, caspase 3 activity and COX-2 expression). [ Time Frame: 6 months ]
- Colonic microbiome composition, after curcumin therapy. [ Time Frame: 6 months ]
- Duodenal adenoma number. [ Time Frame: 6 months ]
- Duodenal adenoma size. [ Time Frame: 6 months ]
- Curcumin and curcuminoid levels in blood. [ Time Frame: 6 months ]
- Curcumin and curcuminoid levels in urine. [ Time Frame: 6 months ]
inclusion criteria:
• Eligible Ages: 18 - 70
• Eligible Sexes: all
• An established clinical diagnosis of Familial Polyposis based on accepted clinical/ endoscopic and an identified APC or MUTYH mutation
• Age 18-70 years.
• Willing and able to give written consent.
• At least 5 polyps, 2mm or lrager, with at least one larger then 4mm but not more then 20mm.
• Colonic polyp burden that can be estimated by either counting or photographing(photo or video).
exclusion criteria:
• Pregnant or nursing women.
• Stable does of any COX inhibitor drugs for more than 3 months prior to study entry,.
• Concomitant severe or uncontrolled cardiovascular, hepatic, renal or metabolic disease.
• Known allergy to curcumin.
• Anticipated surgery within 6 months
• Diagnosed polyps of high grade dysplasia or of adenocarcinomas in the GI on screening colonoscopy.
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