Bioavailability of N-acylethanolamines: an Ileostomy Study (NAE Study) (NAE)

Bioavailability of N-acylethanolamines: an Ileostomy Study.

The endocannabinoids (ECs) and N-acylethanolamines (NAEs) are a group of endogenous lipid mediators which have a pleiotropic activity in the body modulating several biological pathways such as: appetite cues, food intake, blood pressure, inflammation, glycaemia, cognition and immunity. The ECs consist of N-arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG). They may have agonist activity on cannabinoid receptors CB1 and CB2 which are located in the central nervous system (CNS) and in peripheral tissues such as in the enteric nervous system (ENS), in the liver and in the adipose tissue. NAEs are known as "endocannabinoid-like" molecules and include oleoylethanolamine (OEA), linoleylethanolamine (LEA), and palmitoyletahanolamine (PEA). Evidence indicates that diet composition may affect fasting and post-prandial plasma ECs, N-acylphosphatidylethanolamines (NAPEs) and NAEs profile due to the content of their precursors, fatty acids and amines.

It is hypothesized that the concentration of NAPEs, NAEs and ECs in a meal could influence the intestinal concentrations of these lipid mediators that could bind the receptors located on the intestinal mucosa and in turn, differently modulate appetite and energy metabolism.

The study is an acute randomized crossover feeding study in ileostmists (n=14), having a breakfast meal low or high in NAPEs, NAEs and ECs. The meals are designed on a database published by our collaborators (University of Naples) and detailed in the research proposal. Concentrations of NAEs and ECs in urine, plasma and ileal fluid, beside the blood glucose, hormonal response, appetite feelings and food intake will be monitored over the experimental days.

Study Overview

• Status: Recruiting
• Conditions: Healthy Nutrition
• Intervention / Treatment: Dietary supplement: High-N-acylethanolamine meal; Dietary supplement: Low-N-acylethanolamine meal

• Study Type: Interventional
• Enrollment (Anticipated): 14
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christopher Gill; Phone Number: +44 28 7012 3181; Email: c.gill@ulster.ac.uk

Study Locations

• United Kingdom
  • Co.Londonderry
    • Coleraine, Co.Londonderry, United Kingdom, BT52 1SA
      • Recruiting
      • Human Intervention Studies Unit, Ulster University
      • Contact: Ruth K Price; Phone Number: +442870123878; Email: rk.price@ulster.ac.uk
      • Contact: Julie J Sittlington; Phone Number: +442870124101; Email: jj.sittlington@ulster.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participant must have previously undergone an ileostomy and be more than 1.5-years post-operative
• Male or female
• Aged 18-70 years at recruitment

Exclusion Criteria:

• Participants not undergone an ileostomy and/or is less 1.5-years post-operative
• Adults <18 or >70 years at recruitment
• Pregnant/lactating female
• Current smokers
• Lactose intolerant
• Allergic to nuts

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-N-acylethanolamines meal; Milk (150 mL), white bread (46 g), jam (10 g), cocoa powder (15 g), whole-grain cereals (30 g).	Dietary supplement: High-N-acylethanolamine meal; Milk (150 mL), white bread (46 g), jam (10 g), cocoa powder (15 g), whole-grain cereals (30 g).
Active Comparator: Low-N-acylethanolamines meal; Milk (150 mL), whole-grain bread (80 g), jam (10 g), butter (5 g), instant coffee (2 g), dried apples (30 g).	Dietary supplement: Low-N-acylethanolamine meal; Milk (150 mL), whole-grain bread (80 g), jam (10 g), butter (5 g), instant coffee (2 g), dried apples (30 g).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
N-acylphosphatidylethanolamines (NAPEs) levels in biofluids	Significant changes from baseline in plasma, urines and, Ileal fluids levels of NAPEs by HPLC-MS analysis.	Change from baseline at 2, 4, 6 and, 8 hours after breakfast intake
N-acylethanolamines (NAEs) levels in biofluids	Significant changes from baseline in plasma, urines and, Ileal fluids levels of NAEs by HPLC-MS analysis.	Change from baseline at 2, 4, 6 and, 8 hours after breakfast intake
Endocannabinoids levels in biofluids	Significant changes from baseline in plasma, urines and, Ileal fluids levels of ECs by HPLC-MS analysis.	Change from baseline at 2, 4, 6 and, 8 hours after breakfast intake

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycaemia	Measure of glycaemia by using a bedside glucometer.	Change from baseline at 2, 4, 6 and, 8 hours after breakfast intake
Appetite sensations	Significant changes from baseline in hunger, satiety, fullness and prospective of consumption.	Change from baseline at 2, 4, 6 and, 8 hours after breakfast intake
Glucagon-like peptide 1 (GLP-1) plasmatic levels	Measure of GLP-1 by using of Luminex kits in plasma samples pre-treated with protease inhibitor cocktail.	Change from baseline at 2, 4, 6 and, 8 hours after breakfast intake
Glucose-dependent insulinotropic peptide (GIP) plasmatic levels	Measure of GIP by mean of Luminex kits in plasma samples pre-treated with protease inhibitor cocktail.	Change from baseline at 2, 4, 6 and, 8 hours after breakfast intake
Insulin plasmatic levels	Measure of insulin by mean of Luminex kits in plasma samples pre-treated with protease inhibitor cocktail.	Change from baseline at 2, 4, 6 and, 8 hours after breakfast intake
Glucagon plasmatic levels.	Measure of glucagon by mean of Luminex kits in plasma samples pre-treated with protease inhibitor cocktail.	Change from baseline at 2, 4, 6 and, 8 hours after breakfast intake
C-peptide plasmatic levels.	Measure of c-peptide by mean of Luminex kits in plasma samples pre-treated with protease inhibitor cocktail.	Change from baseline at 2, 4, 6 and, 8 hours after breakfast intake
Ghrelin plasmatic levels.	Measure of ghrelin by mean of Luminex kits in plasma samples pre-treated with protease inhibitor cocktail.	Change from baseline at 2, 4, 6 and, 8 hours after breakfast intake
Leptin plasmatic levels	Measure of leptin by mean of Luminex kits in plasma samples pre-treated with protease inhibitor cocktail.	Change from baseline at 2, 4, 6 and, 8 hours after breakfast intake
Energy intake during a buffet meal test	Kilojoules	0 hours
Gut microbiota composition	Microbiota composition will be determined by high throughput sequencing of the 16S ribosomal ribonucleic acid (rRNA) gene. The massive number of sequences obtained will be analyzed by using state of the art bioinformatics tools and the presence and relative abundance of the microbial species occurring in each sample will be determined.	Change from baseline at 2, 4, 6 and, 8 hours after breakfast intake

Collaborators and Investigators

• Sponsor: University of Ulster
• Collaborators: Federico II University

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2023
• Primary Completion (Anticipated): June 13, 2024
• Study Completion (Anticipated): June 13, 2024

Study Registration Dates

• First Submitted: February 28, 2023
• First Submitted That Met QC Criteria: May 2, 2023
• First Posted (Estimate): May 5, 2023

Study Record Updates

• Last Update Posted (Estimate): May 5, 2023
• Last Update Submitted That Met QC Criteria: May 2, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Bioavailability,; Lipid mediators; Nutrient sensing,; N-acylethanolamines,; Satiety.
• Other Study ID Numbers: REC/19/0096

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