Use of Beetroot Juice to Protect Against Postoperative Ileus Following Colorectal Surgery: BEET IT Study

Postoperative Ileus Clinical Trial

— BEET IT  

Official title:

Use of Beetroot Juice to Protect Against Postoperative Ileus Following Colorectal Surgery: BEET IT Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05133024
• Other study ID #: BC-06366
• Status: Recruiting
• Phase: Phase 2
• Start date: March 31, 2021
• Est. completion date: June 30, 2025

Study information

• Verified date: October 2023
• Source: University Hospital, Ghent
• Contact: Wim Ceelen, MD, PhD
• Phone: 093326251
• Email: wim.ceelen[@]ugent.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 170
• Est. completion date: June 30, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Ileus
• Postoperative Ileus

Intervention

Dietary Supplement:
• concentrated beetroot juice
Nitrate supplementation; natural source of dietary nitrate

Locations

Country	Name	City	State
Belgium	Antwerp University Hospital	Edegem
Belgium	Hospital East-Limburg	Genk
Belgium	AZ Sint-Lucas Ghent	Gent
Belgium	Ghent University Hospital	Ghent
Belgium	University Hospital Leuven	Leuven

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Ghent	Research Foundation Flanders

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	hours after the end of surgery (suture)
Secondary	First passage of flatus	recorded in postoperative days (standard of care) and hours (self-reported in the patient diary)	first occurence after the end of surgery (suture)
Secondary	First passage of stool	recorded in postoperative days (standard of care) and hours (self-reported in the patient diary)	first occurence after the end of surgery (suture)
Secondary	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 occurence after the end of surgery (suture)
Secondary	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 occurence after the end of surgery (suture)
Secondary	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)	first occurence after the end of surgery (suture)
Secondary	Incidence and recovery of PPOI	according to the PPOI definition of Vather et al., 2013	until hospital discharge after surgery
Secondary	Postoperative length of hospital stay	from the end of surgery (day 0) until discharge (alive) from hospital, recorded in days (standard of care)	until hospital discharge after surgery
Secondary	Number and types of postoperative complications	according to Clavien-Dindo, CCI	until 3 months after surgery
Secondary	Levels of specific biomarkers in blood, tissues and/or feces	markers for inflammation and oxidative stress, NO bioavailability, intestinal barrier function and permeability	4 time points: (1) inclusion, (2) day of surgery, (3) postoperative day 1, (4) postoperative day 3