Use of Beetroot Juice to Protect Against Postoperative Ileus Following Colorectal Surgery: BEET IT Study (BEET IT)
Primary Purpose
Postoperative Ileus
Status
Recruiting
Phase
Phase 2
Locations
Belgium
Study Type
Interventional
Intervention
concentrated beetroot juice
Sponsored by
About this trial
This is an interventional prevention trial for Postoperative Ileus
Eligibility Criteria
Inclusion Criteria:
- Adult patients undergoing elective colonic and upper rectum laparoscopic surgery requiring an anastomosis, without the need of conversion
Exclusion Criteria:
General:
- < 18 years of age
- Pregnancy or breast feeding
Medical:
- Psychiatric pathology capable of affecting comprehension and judgment faculty
- History of inflammatory bowel disease
- Chronic vascular disease affecting the intestines
- Chronic constipation (<= 2 bowel movements/week)
- Previous abdominal or pelvic radiation treatment
- Recent (< 3 months before inclusion) or current intra-abdominal infection or inflammation (e.g. diverticulitis, appendicitis, cholecystitis)
- Use of gut motility influencing agents (e.g. tricyclic antidepressants, chronic use of laxatives)
- Use of nitrates (e.g. isosorbide dinitrate, nitroglycerin), including daily consumption of beetroot juice (unless stopped for a month prior to the intervention period)
- Hypotension (< 100/60 mmHg)
- Uncontrolled diabetes mellitus
- Renal or hepatic insufficiency
- Known allergies or intolerances to beetroot, nitrates/nitrites
- Enrollment in other clinical trials/experiments, unless approved by the Ethics Committee(s)
Surgical:
- History of prior colorectal surgery
- Emergency surgery
- Open surgery
- Colorectal surgery not requiring an anastomosis (e.g. colotomy, wedge resection)
- More than 1 bowel anastomosis planned
- Concomitant surgical procedures required (e.g. resection of liver or lung metastases)
- Protective stoma planned
Sites / Locations
- Antwerp University HospitalRecruiting
- Hospital East-Limburg
- AZ Sint-Lucas GhentRecruiting
- Ghent University HospitalRecruiting
- University Hospital LeuvenRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
beetroot juice
nitrate-depleted beetroot juice
Arm Description
Brand: BEET IT sport NITRATE 400 concentrated beetroot shot (James White Drinks Ltd.) Dosage regimen: 7 shots of 70 mL, once daily in the morning, on 7 consecutive days before surgery
Brand: BEET IT sport NITRATE 400 nitrate-depleted concentrated beetroot shot (James White Drinks Ltd.) Dosage regimen: 7 shots of 70 mL, once daily in the morning, on 7 consecutive days before surgery
Outcomes
Primary Outcome Measures
Postoperative recovery of gastrointestinal (GI) function
composite endpoint requiring recovery of both upper GI functions (tolerance of a solid diet) and lower GI functions (passage of flatus and stool)
Secondary Outcome Measures
First passage of flatus
recorded in postoperative days (standard of care) and hours (self-reported in the patient diary)
First passage of stool
recorded in postoperative days (standard of care) and hours (self-reported in the patient diary)
First tolerance of liquids
liquids: no chewing required, can be quickly swallowed as such, can be ingested with a straw (e.g. water, coffee, tea, juice, soda), recorded in postoperative days (standard of care) and hours (self-reported in the patient diary)
First tolerance of a semi-solid diet
semi-solid food: no or limited biting and chewing required, can be easily swallowed, usually ingested with a spoon or fork (e.g. yoghurt, eggs, soft cheeses), recorded in postoperative days (standard of care) and hours (self-reported in the patient diary)
First tolerance of a solid diet
solid food: proper and sustained biting and chewing required, cannot be swallowed as such, a knife is usually required to cut the food (e.g. steak, raw vegetables, crisp fruit), recorded in postoperative days (standard of care) and hours (self-reported in the patient diary)
Incidence and recovery of PPOI
according to the PPOI definition of Vather et al., 2013
Postoperative length of hospital stay
from the end of surgery (day 0) until discharge (alive) from hospital, recorded in days (standard of care)
Number and types of postoperative complications
according to Clavien-Dindo, CCI
Levels of specific biomarkers in blood, tissues and/or feces
markers for inflammation and oxidative stress, NO bioavailability, intestinal barrier function and permeability
Full Information
NCT ID
NCT05133024
First Posted
September 27, 2021
Last Updated
October 20, 2023
Sponsor
University Hospital, Ghent
Collaborators
Research Foundation Flanders
1. Study Identification
Unique Protocol Identification Number
NCT05133024
Brief Title
Use of Beetroot Juice to Protect Against Postoperative Ileus Following Colorectal Surgery: BEET IT Study
Acronym
BEET IT
Official Title
Use of Beetroot Juice to Protect Against Postoperative Ileus Following Colorectal Surgery: BEET IT Study
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 31, 2021 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
June 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Ghent
Collaborators
Research Foundation Flanders
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
The goal of the BEET IT study is to examine if preoperative intake of beetroot juice can ameliorate gastrointestinal (GI) recovery after colorectal surgery and thereby help to reduce the duration of postoperative ileus (POI) and prevent prolonged POI. Adult patients undergoing laparoscopic colorectal surgery are randomized 1:1 to consume either concentrated beetroot juice (active intervention) or nitrate-depleted concentrated beetroot juice (placebo) during the week before their surgery. Blood, tissue and/or fecal samples are collected at specific time points pre- and/or postoperatively to study markers related to inflammation, oxidative stress and GI function. Patients are followed from the week before surgery (start of the intervention) until 3 months post-surgery. The study takes place at 5 hospitals in Flanders, Belgium.
Detailed Description
Postoperative ileus (POI), a transient impairment of gastrointestinal (GI) motility, remains one of the most common complications following abdominal surgery. It is characterized by the presence of nausea and vomiting, the inability to tolerate oral diet, abdominal distension and delayed passage of flatus and stool. POI usually resolves within 3 to 5 days, but when prolonged, it can lead to increased morbidity, prolonged hospitalization and increased healthcare costs. In patients undergoing colorectal surgery, the reported incidence of prolonged POI (PPOI) is 10.2%. Prevention and treatment remains mainly supportive and no single effective treatment is currently available. Because of its multifactorial origin and possible exogenous factors, prevention and treatment generally requires a multimodal approach. Many of these strategies are part of the Enhanced Recovery after Surgery (ERAS) program. The pathophysiology of POI is marked by an acute neurogenic phase followed by a prolonged inflammatory phase and alterations in the enteric neurotransmission. The pathogenesis involves inflammation and oxidative stress, similar to ischemia/reperfusion (I/R) injury. Both I/R injury and POI are associated with downregulation of nitric oxide (NO) synthases. In this sense, beetroot juice holds considerable promise. Beetroot is a rich source of inorganic nitrate. Consumption of nitrate-rich foods increases the concentration of NO metabolites in the blood and tissues via the enterosalivary nitrate-nitrite-NO pathway, independently of the traditional pathway via the endogenous NOS enzymes, which tends to become less effective in older age and in environments wherein oxygen availability is limited such as during hypoxia and I/R injury. Interest goes to the effects of preoperative beetroot juice supplementation on postoperative GI recovery and POI duration after laparoscopic colorectal surgery. A proof of concept study with 12 patients at our lab already showed promising results. We now want to validate the results in a bigger group of patients via a multicentric double-blind randomized controlled prospective phase II study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postoperative Ileus
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Multicentric double-blind randomized controlled prospective phase II study
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Beetroot juice bottles are delivered at the central investigational site in labeled boxes indicating whether they are active or control juice. The bottles themselves are identical in appearance and only distinguishable by the manufacturer through the production code. Blinding of the juices is done by an independent party who is responsible for removing the labels, indicating whether the juices are active or nitrate-depleted juice, from the boxes, and assigning an intervention letter code to active or control beetroot juice as 'A' or 'B', without revealing which is which. Sets of 7 bottles, corresponding with the dosage regimen, from A or B according to the randomization list made by an independent statistician, are then labelled with an unique randomization letter code comprising of 2 randomly generated letters, followed by an underscore and a numerical index from 1 to 7 (e.g. AX_1,…, AX_7) to assure allocation concealment.
Allocation
Randomized
Enrollment
170 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
beetroot juice
Arm Type
Active Comparator
Arm Description
Brand: BEET IT sport NITRATE 400 concentrated beetroot shot (James White Drinks Ltd.) Dosage regimen: 7 shots of 70 mL, once daily in the morning, on 7 consecutive days before surgery
Arm Title
nitrate-depleted beetroot juice
Arm Type
Placebo Comparator
Arm Description
Brand: BEET IT sport NITRATE 400 nitrate-depleted concentrated beetroot shot (James White Drinks Ltd.) Dosage regimen: 7 shots of 70 mL, once daily in the morning, on 7 consecutive days before surgery
Intervention Type
Dietary Supplement
Intervention Name(s)
concentrated beetroot juice
Other Intervention Name(s)
BEET IT sport NITRATE 400 concentrated beetroot shot
Intervention Description
Nitrate supplementation; natural source of dietary nitrate
Primary Outcome Measure Information:
Title
Postoperative recovery of gastrointestinal (GI) function
Description
composite endpoint requiring recovery of both upper GI functions (tolerance of a solid diet) and lower GI functions (passage of flatus and stool)
Time Frame
hours after the end of surgery (suture)
Secondary Outcome Measure Information:
Title
First passage of flatus
Description
recorded in postoperative days (standard of care) and hours (self-reported in the patient diary)
Time Frame
first occurence after the end of surgery (suture)
Title
First passage of stool
Description
recorded in postoperative days (standard of care) and hours (self-reported in the patient diary)
Time Frame
first occurence after the end of surgery (suture)
Title
First tolerance of liquids
Description
liquids: no chewing required, can be quickly swallowed as such, can be ingested with a straw (e.g. water, coffee, tea, juice, soda), recorded in postoperative days (standard of care) and hours (self-reported in the patient diary)
Time Frame
first occurence after the end of surgery (suture)
Title
First tolerance of a semi-solid diet
Description
semi-solid food: no or limited biting and chewing required, can be easily swallowed, usually ingested with a spoon or fork (e.g. yoghurt, eggs, soft cheeses), recorded in postoperative days (standard of care) and hours (self-reported in the patient diary)
Time Frame
first occurence after the end of surgery (suture)
Title
First tolerance of a solid diet
Description
solid food: proper and sustained biting and chewing required, cannot be swallowed as such, a knife is usually required to cut the food (e.g. steak, raw vegetables, crisp fruit), recorded in postoperative days (standard of care) and hours (self-reported in the patient diary)
Time Frame
first occurence after the end of surgery (suture)
Title
Incidence and recovery of PPOI
Description
according to the PPOI definition of Vather et al., 2013
Time Frame
until hospital discharge after surgery
Title
Postoperative length of hospital stay
Description
from the end of surgery (day 0) until discharge (alive) from hospital, recorded in days (standard of care)
Time Frame
until hospital discharge after surgery
Title
Number and types of postoperative complications
Description
according to Clavien-Dindo, CCI
Time Frame
until 3 months after surgery
Title
Levels of specific biomarkers in blood, tissues and/or feces
Description
markers for inflammation and oxidative stress, NO bioavailability, intestinal barrier function and permeability
Time Frame
4 time points: (1) inclusion, (2) day of surgery, (3) postoperative day 1, (4) postoperative day 3
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult patients undergoing elective colonic and upper rectum laparoscopic surgery requiring an anastomosis, without the need of conversion
Exclusion Criteria:
General:
< 18 years of age
Pregnancy or breast feeding
Medical:
Psychiatric pathology capable of affecting comprehension and judgment faculty
History of inflammatory bowel disease
Chronic vascular disease affecting the intestines
Chronic constipation (<= 2 bowel movements/week)
Previous abdominal or pelvic radiation treatment
Recent (< 3 months before inclusion) or current intra-abdominal infection or inflammation (e.g. diverticulitis, appendicitis, cholecystitis)
Use of gut motility influencing agents (e.g. tricyclic antidepressants, chronic use of laxatives)
Use of nitrates (e.g. isosorbide dinitrate, nitroglycerin), including daily consumption of beetroot juice (unless stopped for a month prior to the intervention period)
Hypotension (< 100/60 mmHg)
Uncontrolled diabetes mellitus
Renal or hepatic insufficiency
Known allergies or intolerances to beetroot, nitrates/nitrites
Enrollment in other clinical trials/experiments, unless approved by the Ethics Committee(s)
Surgical:
History of prior colorectal surgery
Emergency surgery
Open surgery
Colorectal surgery not requiring an anastomosis (e.g. colotomy, wedge resection)
More than 1 bowel anastomosis planned
Concomitant surgical procedures required (e.g. resection of liver or lung metastases)
Protective stoma planned
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wim Ceelen, MD, PhD
Phone
093326251
Ext
+32
Email
wim.ceelen@ugent.be
First Name & Middle Initial & Last Name or Official Title & Degree
Barbara Cornillie, MSc
Email
barbara.cornillie@ugent.be
Facility Information:
Facility Name
Antwerp University Hospital
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guy Hubens, MD, PhD
Email
guy.hubens@uza.be
First Name & Middle Initial & Last Name & Degree
Lieselotte Iket
Email
lieselotte.iket@uza.be
Facility Name
Hospital East-Limburg
City
Genk
ZIP/Postal Code
3600
Country
Belgium
Individual Site Status
Active, not recruiting
Facility Name
AZ Sint-Lucas Ghent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kjell Fierens, MD
Email
kjell.fierens@azsintlucas.be
First Name & Middle Initial & Last Name & Degree
Barbara Vincent
Email
barbara.vincent@azsintlucas.be
Facility Name
Ghent University Hospital
City
Ghent
ZIP/Postal Code
9000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Barbara Cornillie, MSc
Email
barbara.cornillie@ugent.be
First Name & Middle Initial & Last Name & Degree
Sarah Cosyns, PhD
Email
sarah.cosyns@ugent.be
Facility Name
University Hospital Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Albert Wolthuis, MD, PhD
Email
albert.wolthuis@uzleuven.be
First Name & Middle Initial & Last Name & Degree
Isabelle Terrasson
Email
isabelle.terrasson@uzleuven.be
12. IPD Sharing Statement
Learn more about this trial
Use of Beetroot Juice to Protect Against Postoperative Ileus Following Colorectal Surgery: BEET IT Study
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