Turmeric Supplementation on Polyp Number and Size in Patients With Familial Adenomatous Polyposis.
Primary Purpose
Familial Adenomatous Polyposis, FAP, FAP Gene Mutation
Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Wholistic Turmeric capsules
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Familial Adenomatous Polyposis focused on measuring Turmeric, Curcumin, colorectal polyps, colorectal neoplasia, mutyh mutation, apc mutation
Eligibility Criteria
Inclusion Criteria:
- 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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Wholistic Turmeric capsules
Placebo
Arm Description
Oral capsules of wholistic Turmeric capsules (Pukka herbs) (each capsule 100 mg curcumin) divided twice daily, or an identical placebo in 2 divided doses daily all taken before meals. Pukka's Wholistic Turmeric
Identical placebo capsules
Outcomes
Primary Outcome Measures
Number of polyps
Size of polyps
Secondary Outcome Measures
Histological apoptosis assays in frozen polyps and normal tissue (such as KI67, caspase 3 activity and COX-2 expression).
Histological proliferation assays in frozen polyps and normal tissue (such as KI67, caspase 3 activity and COX-2 expression).
Colonic microbiome composition, after curcumin therapy.
Duodenal adenoma number.
Duodenal adenoma size.
Curcumin and curcuminoid levels in blood.
Curcumin and curcuminoid levels in urine.
Full Information
NCT ID
NCT03061591
First Posted
February 14, 2017
Last Updated
February 19, 2017
Sponsor
Tel-Aviv Sourasky Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT03061591
Brief Title
Turmeric Supplementation on Polyp Number and Size in Patients With Familial Adenomatous Polyposis.
Official Title
Efficacy of Wholistic Turmeric Supplementation on Polyp Number and Size in Patients With Familial Adenomatous Polyposis A Randomized, Double Blinded, Placebo Controlled Study
Study Type
Interventional
2. Study Status
Record Verification Date
February 2017
Overall Recruitment Status
Unknown status
Study Start Date
April 2017 (Anticipated)
Primary Completion Date
April 2018 (Anticipated)
Study Completion Date
April 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Tel-Aviv Sourasky Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
A Phase 2, randomized, double blind, placebo controlled trial for the effectivness of wholistic turmeric supplementation on polyp burden mong patients with Familial Adenomatouse Polyposis (FAP). Fourty Patients will be randomly assigned in a 1:1 ratio to recieve treatment with 8 capsuls (2*4 capsuls/day) of wholistic Turmeric capsules (Pukka herbs) or placebo for six months.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Familial Adenomatous Polyposis, FAP, FAP Gene Mutation
Keywords
Turmeric, Curcumin, colorectal polyps, colorectal neoplasia, mutyh mutation, apc mutation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
6 months of Curcumin vs. placebo treatment outcomes will be compared.
Masking
ParticipantCare ProviderInvestigatorOutcomes 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.
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Wholistic Turmeric capsules
Arm Type
Active Comparator
Arm Description
Oral capsules of wholistic Turmeric capsules (Pukka herbs) (each capsule 100 mg curcumin) divided twice daily, or an identical placebo in 2 divided doses daily all taken before meals.
Pukka's Wholistic Turmeric
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Identical placebo capsules
Intervention Type
Dietary Supplement
Intervention Name(s)
Wholistic Turmeric capsules
Intervention Description
Oral capsules of wholistic Turmeric capsules (Pukka herbs) curcumin (each capsule 0.5100 m gr curcumin) for a total of 4 gr/d divided twice daily.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo capsules
Primary Outcome Measure Information:
Title
Number of polyps
Time Frame
6 months
Title
Size of polyps
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Histological apoptosis assays in frozen polyps and normal tissue (such as KI67, caspase 3 activity and COX-2 expression).
Time Frame
6 months
Title
Histological proliferation assays in frozen polyps and normal tissue (such as KI67, caspase 3 activity and COX-2 expression).
Time Frame
6 months
Title
Colonic microbiome composition, after curcumin therapy.
Time Frame
6 months
Title
Duodenal adenoma number.
Time Frame
6 months
Title
Duodenal adenoma size.
Time Frame
6 months
Title
Curcumin and curcuminoid levels in blood.
Time Frame
6 months
Title
Curcumin and curcuminoid levels in urine.
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Naomi Fliss, MSc
Phone
97236974458
Email
naomifl@tlvmc.gov.il
First Name & Middle Initial & Last Name or Official Title & Degree
Sivan Kaspi, RD
Phone
97236974458
Email
sivanah@tlvmc.gov.il
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Revital Kariv, MD
Organizational Affiliation
Tel Aviv SMC
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
16757216
Citation
Cruz-Correa M, Shoskes DA, Sanchez P, Zhao R, Hylind LM, Wexner SD, Giardiello FM. Combination treatment with curcumin and quercetin of adenomas in familial adenomatous polyposis. Clin Gastroenterol Hepatol. 2006 Aug;4(8):1035-8. doi: 10.1016/j.cgh.2006.03.020. Epub 2006 Jun 6.
Results Reference
background
PubMed Identifier
12050094
Citation
Perkins S, Verschoyle RD, Hill K, Parveen I, Threadgill MD, Sharma RA, Williams ML, Steward WP, Gescher AJ. Chemopreventive efficacy and pharmacokinetics of curcumin in the min/+ mouse, a model of familial adenomatous polyposis. Cancer Epidemiol Biomarkers Prev. 2002 Jun;11(6):535-40.
Results Reference
background
PubMed Identifier
22953026
Citation
Pettan-Brewer C, Morton J, Mangalindan R, Ladiges W. Curcumin suppresses intestinal polyps in APC Min mice fed a high fat diet. Pathobiol Aging Age Relat Dis. 2011;1. doi: 10.3402/pba.v1i0.7013. Epub 2011 Jun 1.
Results Reference
background
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Turmeric Supplementation on Polyp Number and Size in Patients With Familial Adenomatous Polyposis.
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