Prophylactic Properties of Carrot Juice in Patients With High-Risk Colorectal Polyps (Px7)

Polyp Prophylactic Properties of Polyacetylenes in Patients With Previous Polypectomy

The goal of this prospective randomized double-blinded bi-national study is to test the prophylactic effect of polyacetylenes from carrots on the population of patients who had a resection of high-risk adenomas of the large bowel.

The main question it aims to answer is: Will carrot juice rich in polyacetylenes inhibit neoplastic transformation and growth in high-risk humans?

Participants will have to drink 100 ml of juice daily after the adenoma resection for 1 year and keep a simple diary/calendar.

Researchers will compare the group with ingestion of FaOH/FaDOH rich carrot juice versus the group consuming placebo juice, to see if the polyacetylenes significantly reduces neoplastic transformation and growth in high-risk patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Cancer Prevention
• Intervention / Treatment: Dietary supplement: Carrot juice from Yellowstone carrots cultivars; Dietary supplement: Placebo juice

Detailed Description

The study is a prospective double-blinded randomized controlled trial carried out in four centers: one Danish (Department of Surgery, Odense University Hospital - OUH) and three Swedish (Södersykehuset, Stockholm - KUH; University Hospital, Uppsala - UUH; Sahlgrenska Goteborg - SUH).

The investigators will organize two parallel arms of 400 patients: an intervention arm (consumption of 100 ml active carrot juice daily) and a control arm (consumption of 100 ml placebo juice daily) in a 1:1 randomized allocation ratio for 1 year. The project is structured in 2 working packages (WP):

1. The clinical trial (including cultivation and quality control of carrots and juice production; quantification of FaOH and FaDOH in the carrot and the placebo juice and the randomized trial)
2. The assessment of patient compliance and ways to improve it (Umeå Institute of Design, Umeå University - UMU).

The investigators hypothesize that the difference between the active arm (carrot juice) and the control arm (placebo juice) measured by a combined endpoint of total number of recurrent adenomas multiplied with mean size of recurrent adenomas will mediate a 20% reduction or larger in both size and number.

Outcomes will be investigated through standard colonoscopy report, questionnaires, calendars and diares.

The randomization is stratified by inclusion center, each having its own block of 50/50 distribution between active and placebo arm.

The patients will collect 8 L of juice, the diary, calendar and a questionnaire every 2 months. At this meeting the patients will also have a follow-up discussion with the project nurse.

All patients will undergo colonoscopy after one year from the resection and in addition, for the piecemeal resections there will also be a local follow up colonoscopy after 3 months. Information about recurrence, the number of polyps, polyp size and characterization will be registered in the database. Full compliance is defined as consumption of > 75% of the juice delivered. Consumption data for all patients will be kept for compliance analysis.

Data will be analyzed using exact methods for binomial data. The combined endpoint will be the total number of recurrent adenomas multiplied with mean size of recurrent adenomas in the relevant treatment group.

Participation is voluntary with no economic compensation, and the patients are informed orally and in writing according to the information accepted by the ethics committee.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gunnar Baatrup, Professor; Phone Number: +4520575154; Email: Gunnar.Baatrup@rsyd.dk
• Study Contact Backup: Name: Alexandra D Agache, Postdoc; Phone Number: +4520355717; Email: Alexandra.Agache@rsyd.dk

Study Locations

• Denmark
  • Odense, Denmark, 5000
    • Department of Surgery, Odense University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Any type of resection for adenomas larger than 20 mm in size (endoscopically evaluated).
2. Acceptance of the treatment and follow-up program.
3. Capability to understand and follow the instructions.

Exclusion Criteria:

1. Patients allocated to "high-risk" group because of many small polyps (>4).
2. Pregnancy.
3. Known relevant allergies.
4. Chronic consumption of COX inhibitors (Aspirin, Celecoxib, Ibuprofen, Diclofenac, Ketoprofen, Ketorolac, Indometacin, Naproxen, Piroxicam) or immunosuppresive agents (Methotrexate, Azathioprine or glucocorticoids)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Carrot juice; The cultivation of "Yellowstone" carrots will be conducted by DanRoots A/S.DanRoots, Organic Vegetables, Bjerringbro, Denmark.Juice is produced and taste corrected by Orskov Food, Denmark in collaboration with Naturfrisk, Ørbæk. Analysis of carrot juice for falcarinol and falcarindiol content will be done at random from 10 samples leaving the factory and 10 samples collected after 30 days storage at participant's homes for each batch.	Dietary supplement: Carrot juice from Yellowstone carrots cultivars; Consumption of 100 ml of carrot juice daily for 1 year
Placebo Comparator: Placebo juice; Placebo juice is produced from natural flavours and taste corrected by Orskov Food, Denmark in collaboration with Naturfrisk, Ørbæk. The taste is corrected to prevent enabling differentiation between carrot juice and placebo.	Dietary supplement: Placebo juice; Consumption of 100 ml of placebo juice daily for 1 year

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and size of polyps found at the one-year follow up colonoscopy	The combined endpoint (number x size of polyps) after 1 year of treatment.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Polyp number and size in relation to carrot consumption measurement	A covariate analysis of carrot consumption (concentration of polyacetylenes expoure)measured through diaries, calendar and questionnaires and the findings at the 1 year colonoscopy	1 year
Compliance rate (Juice consumption level)	Assesment of compliance rate through diary, calendar marks and questionnaire	1 year
Side effects	Assesment of side effects through questionnaire	1 year
Acceptability of treatment	Assesment of acceptance and ways to improve carrot products through diary and questionnaire	1 year

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Collaborators: Karolinska Institutet; Umeå University; Sahlgrenska University Hospital, Sweden; Svendborg Hospital; Uppsala University Hospital

Publications and helpful links

General Publications

• Deding U, Baatrup G, Kaalby L, Kobaek-Larsen M. Carrot Intake and Risk of Developing Cancer: A Prospective Cohort Study. Nutrients. 2023 Jan 29;15(3):678. doi: 10.3390/nu15030678.
• Schmiech L. Strukturafklârung und qualitative Studien zu Bitterstoffen und Polyacetylenen in Karitten. Verlag Dr. Hut, 2011, ISBN 978-3-8439-0069-0
• Deding U, Clausen BH, Al-Najami I, Baatrup G, Jensen BL, Kobaek-Larsen M. Effect of Oral Intake of Carrot Juice on Cyclooxygenases and Cytokines in Healthy Human Blood Stimulated by Lipopolysaccharide. Nutrients. 2023 Jan 26;15(3):632. doi: 10.3390/nu15030632.
• Jakobsen U, Kobaek-Larsen M, Kjoller KD, Antonsen S, Baatrup G, Trelle MB. Quantification of the anti-neoplastic polyacetylene falcarinol from carrots in human serum by LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2022 Nov 1;1210:123440. doi: 10.1016/j.jchromb.2022.123440. Epub 2022 Sep 6.
• Deding U, Baatrup G, Christensen LP, Kobaek-Larsen M. Carrot Intake and Risk of Colorectal Cancer: A Prospective Cohort Study of 57,053 Danes. Nutrients. 2020 Jan 27;12(2):332. doi: 10.3390/nu12020332.
• Kobaek-Larsen M, Baatrup G, KhataeiNotabi M, El-Houri RB, Pipo-Olle E, Christensen Arnspang E, Christensen LP. Dietary Polyacetylenic Oxylipins Falcarinol and Falcarindiol Prevent Inflammation and Colorectal Neoplastic Transformation: A Mechanistic and Dose-Response Study in A Rat Model. Nutrients. 2019 Sep 14;11(9):2223. doi: 10.3390/nu11092223.
• Kobaek-Larsen M, Nielsen DS, Kot W, Krych L, Christensen LP, Baatrup G. Effect of the dietary polyacetylenes falcarinol and falcarindiol on the gut microbiota composition in a rat model of colorectal cancer. BMC Res Notes. 2018 Jun 27;11(1):411. doi: 10.1186/s13104-018-3527-y.
• Kobaek-Larsen M, El-Houri RB, Christensen LP, Al-Najami I, Frette X, Baatrup G. Dietary polyacetylenes, falcarinol and falcarindiol, isolated from carrots prevents the formation of neoplastic lesions in the colon of azoxymethane-induced rats. Food Funct. 2017 Mar 22;8(3):964-974. doi: 10.1039/c7fo00110j.
• Kobaek-Larsen M, Christensen LP, Vach W, Ritskes-Hoitinga J, Brandt K. Inhibitory effects of feeding with carrots or (-)-falcarinol on development of azoxymethane-induced preneoplastic lesions in the rat colon. J Agric Food Chem. 2005 Mar 9;53(5):1823-7. doi: 10.1021/jf048519s.

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: March 13, 2024
• First Submitted That Met QC Criteria: March 21, 2024
• First Posted (Actual): March 28, 2024

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 324-2023-GB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No