Preoperative Oral ImmunoNuTrition to Improve Surgical Outcomes for IBD Patients (PINT) (PINT)

Preoperative Oral ImmunoNuTrition to Improve Surgical Outcomes for Inflammatory Bowel Disease Patients (PINT): A Randomized Controlled Trial

The central focus of this trial is to understand the effectiveness of Preoperative Immunonutrition (PINT) in improving surgical outcomes for patients with inflammatory bowel disease (IBD). We hypothesize that PINT will reduce post-operative complications in IBD patients undergoing elective surgery with added improvements in length-of-stay (LOS), quality of life (QOL) and patient satisfaction. As a secondary focus, the investigator will aim to better understand the potential mechanism-of-action by which PINT may have its effects through analyses of biomarkers including inflammatory markers, nutritional proteins and the fecal microbiome.

Study Overview

• Status: Withdrawn
• Conditions: Inflammatory Bowel Diseases
• Intervention / Treatment: Drug: Nestle IMPACT Immunonutrition; Other: Arm B- Standard of Care

Detailed Description

Inflammatory bowel disease (IBD), which includes Crohn's and Ulcerative Colitis, is a chronic and costly disease of unknown etiology that now affects over 3.1 million people in the United States. Patients with IBD suffer from lifelong malnutrition, pain and bleeding with added risks of cancers, obstructions and fistulas. There is no known cure and the incidence continues to grow. While treatments are usually medical IBD patients will undergo at least one major surgery during their lifetime. Patients also have particularly poor surgical outcomes with high rates of post-operative complications. In an attempt to improve the risk profile of patients and decrease complications, preoperative total parenteral nutrition (TPN) has been used to optimize IBD patients for surgery. While this approach has been successful the cost and morbidities of TPN prohibit its generalized application. Practical strategies that improve surgical outcomes for IBD patients are urgently needed. Improving nutritional deficiencies before an operation may be a practical way to improve post-operative outcomes. The oral administration of preoperative immunonutrition, is an alternative method to improve nutritional states and may have utility in IBD patients who have particularly severe nutritional deficiencies because of disease-specific issues in malabsorption, maldigestion and loss of appetite.

• Study Type: Interventional
• Phase: Early Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ≥19 years of age
• All races and all genders
• Confirmed diagnosis and history of IBD
• ESPEN Nutritional Risk Scores >=3 and the ESPEN Disease Severity sub-score < 3
• Scheduled for elective surgery via any transabdominal operative approach (i.e. laparoscopic, hand-assisted, robotic, open) with a planned postoperative inpatient stay of at least one night

Exclusion Criteria:

• Failure to meet eligibility criteria
• Patients requiring emergency surgical intervention
• Patients with an American Society of Anesthesiologist physical status of IV or V
• Patients requiring hemodialysis
• Patients with history of myocardial infarction within 6 months
• Patients with a history of asthma
• Patients with cirrhosis or a history of liver disease
• Patients with a present history of dysphagia, pyloric stenosis and esophageal strictures
• Patients unable to consume liquids orally
• Patients allergic or with hypersensitivity reactions to any of the components of the Nestlé IMPACT-Advanced Recovery immunonutritional supplement
• Patients with a history of galactosemia, the inability to metabolize the sugar galactose appropriately
• Patients with bowel obstructions
• Patients with history of HIV or of solid-organ transplant
• Patients who are pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A - Nestle IMPACT Immunonutrition; Treatment Arm A (n=146) - Nestlé IMPACT Advanced Recovery:Along with standard of care nutritional therapy patients will be asked to consume 3 cartons/day for 14 days of Nestle IMPACT Advanced Recovery Immunonutrition.	Drug: Nestle IMPACT Immunonutrition; Along with standard of care nutritional therapy patients (n=146) will be asked to consume 3 cartons/day for 14 days of Nestle IMPACT Advanced Recovery Immunonutrition.; Other Names: Nestle IMPACT Advanced Recovery Immunonutrition
Other: Arm B- Standard of Care; No intervention standard of care nutrition (n=146).	Other: Arm B- Standard of Care; No intervention standard of care nutrition (n=146).; Other Names: Standard of Care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The occurrence of any postoperative complications after surgery	Routine postoperative follow-up for all patients will occur at 2 weeks post discharge. Any serious adverse events or adverse events will be ascertained at the 2 week follow up visit. Complication rates will be divided into major and minor postoperative complications and will be defined as any deviation from the normal postoperative recovery process. Complications will be assessed using the Clavien-Dindo classification in minor and major.	Baseline (day of surgery) to 2 weeks (after surgery)
The occurrence of any postoperative complications after surgery	At the 30 day post-discharge postoperative follow up visit, serious adverse events will be ascertained that may have occurred after the 2 week follow up visit. Patients who are unable to return on the 30-day mark will be called to screen for any post-discharge complications. Complication rates will be divided into major and minor postoperative complications and will be defined as any deviation from the normal postoperative recovery process. Complications will be assessed using the Clavien-Dindo classification in minor and major.	Baseline (day of surgery) to 30 days (after surgery)
The occurrence of any postoperative complications after surgery	Final call to ascertain complications will be at 60 days. Complication rates will be divided into major and minor postoperative complications and will be defined as any deviation from the normal postoperative recovery process. Complications will be assessed using the Clavien-Dindo classification in minor and major.	Baseline (day of surgery) to 60 days (after surgery)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection of the differences in the markers of inflammation interleukin-1-β (IL-1β)	Enzyme-linked immunosorbent assays (ELISA) will be performed to assess whole blood, plasma and serum samples for circulating inflammatory cytokine interleukin-1-β (IL-1β.	Baseline (preoperative visit)
Detection of the differences in the markers of inflammation interleukin-1-β (IL-1β)	Enzyme-linked immunosorbent assays (ELISA) will be performed to assess whole blood, plasma and serum samples for circulating inflammatory cytokine interleukin-1-β (IL-1β.	Baseline (preoperative visit) to day of surgery
Detection of the differences in the markers of inflammation interleukin-1-β (IL-1β)	Enzyme-linked immunosorbent assays (ELISA) will be performed to assess whole blood, plasma and serum samples for circulating inflammatory cytokine interleukin-1-β (IL-1β.	Baseline (preoperative visit) to postoperative day 3
Detection of the differences in the markers of inflammation Interleukin 6 (IL-6)	Enzyme-linked immunosorbent assays (ELISA) will be performed to assess whole blood, plasma and serum samples for circulating inflammatory cytokine interleukin-6 (IL-6).	Baseline (preoperative visit)
Detection of the differences in the markers of inflammation Interleukin 6 (IL-6)	Enzyme-linked immunosorbent assays (ELISA) will be performed to assess whole blood, plasma and serum samples for circulating inflammatory cytokine interleukin-6 (IL-6).	Baseline (preoperative visit) to day of surgery
Detection of the differences in the markers of inflammation Interleukin 6 (IL-6)	Enzyme-linked immunosorbent assays (ELISA) will be performed to assess whole blood, plasma and serum samples for circulating inflammatory cytokine interleukin-6 (IL-6).	Baseline (preoperative visit) to postoperative day 3
Detection of the differences in the markers of inflammation tumor necrosis factor (TNF-α)	Enzyme-linked immunosorbent assays (ELISA) will be performed to assess whole blood, plasma and serum samples for circulating tumor necrosis factor (TNF-α).	Baseline (preoperative visit)
Detection of the differences in the markers of inflammation tumor necrosis factor (TNF-α)	Enzyme-linked immunosorbent assays (ELISA) will be performed to assess whole blood, plasma and serum samples for circulating tumor necrosis factor (TNF-α).	Baseline to day of surgery
Detection of the differences in the markers of inflammation tumor necrosis factor (TNF-α)	Enzyme-linked immunosorbent assays (ELISA) will be performed to assess whole blood, plasma and serum samples for circulating tumor necrosis factor (TNF-α).	Baseline (preoperative visit) to postoperative day 3
Detection of the differences in the markers of inflammation CRP	Immunoassays will be performed with high sensitivity nephelometry to measure CRP levels.	Baseline (preoperative visit)
Detection of the differences in the markers of inflammation CRP	Immunoassays will be performed with high sensitivity nephelometry to measure CRP levels.	Baseline (preoperative visit) to day of surgery
Detection of the differences in the markers of inflammation CRP	Immunoassays will be performed with high sensitivity nephelometry to measure CRP levels.	Baseline (preoperative visit) to postoperative day 3
Detection of the differences in the markers of inflammation nutritional status albumin	Comprehensive metabolic panels will be ordered to assess levels of serum albumin	Baseline (preoperative visit)
Detection of the differences in the markers of inflammation nutritional status albumin	Comprehensive metabolic panels will be ordered to assess levels of serum albumin	Baseline (preoperative visit) to day of surgery
Detection of the differences in the markers of inflammation nutritional status albumin	Comprehensive metabolic panels will be ordered to assess levels of serum albumin	Baseline (preoperative visit) to postoperative day 3
Detection of the differences in the markers of inflammation pre-albumin	Comprehensive metabolic panels will be ordered to assess levels of serum pre-albumin	Baseline (preoperative visit)
Detection of the differences in the markers of inflammation pre-albumin	Comprehensive metabolic panels will be ordered to assess levels of serum pre-albumin	Baseline (preoperative visit) to day of surgery
Detection of the differences in the markers of inflammation pre-albumin	Comprehensive metabolic panels will be ordered to assess levels of serum pre-albumin	Baseline (preoperative visit) to postoperative day 3

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of hospital stay (LOS)	Length of stay will be captured through patient hospitalization files	Baseline (Day of surgery) to day of discharge (approximately 2 to 30 days post surgery)
Patient Quality of Life (QOL)	At the time of the pre-operative visit, following enrollment in the study, participants will complete the Health Related Quality of Life Survey SF-12 questionnaire (HRQoL SF-12). The results of the Health Related Quality of Life Survey SF-12 questionnaire (HRQoL SF-12) will be analyzed and Physical and Mental Health Composite Scores (PCS & MCS) will be computed using the scores of the twelve questions ranging from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.	Baseline (preoperative visit)
Patient Quality of Life (QOL)	Patients at their two week follow up postoperative visit will be given another copy of the HRQoL SF-12 and prepaid return envelopes to be completed and mailed back two weeks after follow up Patients will receive a reminder call to complete the surveys and return in the mail. The results of the Health Related Quality of Life Survey SF-12 questionnaire (HRQoL SF-12) will be analyzed and Physical and Mental Health Composite Scores (PCS & MCS) will be computed using the scores of the twelve questions ranging from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.	Baseline (preoperative) to 30 days
Patient Satisfaction (S-CAHPS)	Will be captured preoperatively with the S-CAHPS. Participants will be asked to complete the Surgical-Consumer Assessment of Healthcare Providers and Systems (S-CAHPS) Survey. The S-CAHPS Surgical Care Survey was developed in 2009 through collaboration of the CAHPS consortium, American College of Surgeons (ACS), the Surgical Quality Alliance (SQA), the American Urological Association (AUA), 11 other surgical subspecialty groups and endorsed by the National Quality Forum (NQF) in 2012. The S-CAHPS is a 47 question survey that addresses patients' preoperative and postoperative experience with surgical care. The CAHPS Surgical Care Survey generates a global rating item, which uses a scale of 0 to 10 to measure respondents' assessments of their surgeon and composite measures (also known as reporting composites), which combine results for closely-related items that have been grouped together.	Baseline (Preoperative)
Patient Satisfaction (S-CAHPS)	Will be captured postoperatively with the S-CAHPS. Participants will be asked to complete the Surgical-Consumer Assessment of Healthcare Providers and Systems (S-CAHPS) Survey. The S-CAHPS Surgical Care Survey was developed in 2009 through collaboration of the CAHPS consortium, American College of Surgeons (ACS), the Surgical Quality Alliance (SQA), the American Urological Association (AUA), 11 other surgical subspecialty groups and endorsed by the National Quality Forum (NQF) in 2012. The S-CAHPS is a 47 question survey that addresses patients' preoperative and postoperative experience with surgical care. The CAHPS Surgical Care Survey generates a global rating item, which uses a scale of 0 to 10 to measure respondents' assessments of their surgeon and composite measures (also known as reporting composites), which combine results for closely-related items that have been grouped together.	Postoperative (After Surgery)
Detection of differences in fecal microbiome	For fecal microbiome analyses, stool will be processed for 16S rRNA sequencing. DNA will be extracted from stool samples using the Fecal DNA Isolation Kit (Zymo Research, Irvine, CA) and processed with PCR amplification on the MiSeq. QIIME and UniFrac will be used to generate a comparative profile of microbial composition. QIIME will be used to assess taxa, alpha and beta diversity. Composition of the microbiome will be compared using UniFrac, Mothur and Genboree to assess for differences between microbiome populations by principal components analysis.	Baseline (Preoperative)
Detection of differences in fecal microbiome	For fecal microbiome analyses, stool will be processed for 16S rRNA sequencing. DNA will be extracted from stool samples using the Fecal DNA Isolation Kit (Zymo Research, Irvine, CA) and processed with PCR amplification on the MiSeq. QIIME and UniFrac will be used to generate a comparative profile of microbial composition. QIIME will be used to assess taxa, alpha and beta diversity. Composition of the microbiome will be compared using UniFrac, Mothur and Genboree to assess for differences between microbiome populations by principal components analysis.	Day of Surgery
Detection of differences in fecal microbiome	For fecal microbiome analyses, stool will be processed for 16S rRNA sequencing. DNA will be extracted from stool samples using the Fecal DNA Isolation Kit (Zymo Research, Irvine, CA) and processed with PCR amplification on the MiSeq. QIIME and UniFrac will be used to generate a comparative profile of microbial composition. QIIME will be used to assess taxa, alpha and beta diversity. Composition of the microbiome will be compared using UniFrac, Mothur and Genboree to assess for differences between microbiome populations by principal components analysis.	2 weeks after surgery (postoperative visit)

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: Gregory D Kennedy, MD,PhD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2020
• Primary Completion (Anticipated): June 1, 2021
• Study Completion (Anticipated): January 1, 2022

Study Registration Dates

• First Submitted: October 20, 2017
• First Submitted That Met QC Criteria: November 1, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): August 17, 2020
• Last Update Submitted That Met QC Criteria: August 13, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Microbiome; Complications; Immunonutrition; Colorectal Surgery; Preoperative nutrition
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Intestinal Diseases
• Other Study ID Numbers: IRB -170222002

Drug and device information, study documents

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