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

• Sponsor: University of Ulster (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05845229
• Collaborator: Federico II University (Other)
• Enrollment: 14
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 16.9
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Nutrition	Dietary Supplement: High-N-acylethanolamine meal; Dietary Supplement: Low-N-acylethanolamine meal	N/A

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Basic Science
• Official Title: Bioavailability of N-acylethanolamines: an Ileostomy Study.
• Actual Study Start Date: Jan 16, 2023
• Anticipated Primary Completion Date: Jun 13, 2024
• Anticipated Study Completion Date: Jun 13, 2024

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures

1. N-acylphosphatidylethanolamines (NAPEs) levels in biofluids [Change from baseline at 2, 4, 6 and, 8 hours after breakfast intake]

   Significant changes from baseline in plasma, urines and, Ileal fluids levels of NAPEs by HPLC-MS analysis.

2. N-acylethanolamines (NAEs) levels in biofluids [Change from baseline at 2, 4, 6 and, 8 hours after breakfast intake]

   Significant changes from baseline in plasma, urines and, Ileal fluids levels of NAEs by HPLC-MS analysis.

3. Endocannabinoids levels in biofluids [Change from baseline at 2, 4, 6 and, 8 hours after breakfast intake]

   Significant changes from baseline in plasma, urines and, Ileal fluids levels of ECs by HPLC-MS analysis.

Secondary Outcome Measures

1. Glycaemia [Change from baseline at 2, 4, 6 and, 8 hours after breakfast intake]

   Measure of glycaemia by using a bedside glucometer.

2. Appetite sensations [Change from baseline at 2, 4, 6 and, 8 hours after breakfast intake]

   Significant changes from baseline in hunger, satiety, fullness and prospective of consumption.

3. Glucagon-like peptide 1 (GLP-1) plasmatic levels [Change from baseline at 2, 4, 6 and, 8 hours after breakfast intake]

   Measure of GLP-1 by using of Luminex kits in plasma samples pre-treated with protease inhibitor cocktail.

4. Glucose-dependent insulinotropic peptide (GIP) plasmatic levels [Change from baseline at 2, 4, 6 and, 8 hours after breakfast intake]

   Measure of GIP by mean of Luminex kits in plasma samples pre-treated with protease inhibitor cocktail.

5. Insulin plasmatic levels [Change from baseline at 2, 4, 6 and, 8 hours after breakfast intake]

   Measure of insulin by mean of Luminex kits in plasma samples pre-treated with protease inhibitor cocktail.

6. Glucagon plasmatic levels. [Change from baseline at 2, 4, 6 and, 8 hours after breakfast intake]

   Measure of glucagon by mean of Luminex kits in plasma samples pre-treated with protease inhibitor cocktail.

7. C-peptide plasmatic levels. [Change from baseline at 2, 4, 6 and, 8 hours after breakfast intake]

   Measure of c-peptide by mean of Luminex kits in plasma samples pre-treated with protease inhibitor cocktail.

8. Ghrelin plasmatic levels. [Change from baseline at 2, 4, 6 and, 8 hours after breakfast intake]

   Measure of ghrelin by mean of Luminex kits in plasma samples pre-treated with protease inhibitor cocktail.

9. Leptin plasmatic levels [Change from baseline at 2, 4, 6 and, 8 hours after breakfast intake]

   Measure of leptin by mean of Luminex kits in plasma samples pre-treated with protease inhibitor cocktail.

10. Energy intake during a buffet meal test [0 hours]

    Kilojoules

11. Gut microbiota composition [Change from baseline at 2, 4, 6 and, 8 hours after breakfast intake]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Human Intervention Studies Unit, Ulster University	Coleraine	Co.Londonderry	United Kingdom	BT52 1SA

Sponsors and Collaborators

• University of Ulster
• Federico II University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Ulster
• ClinicalTrials.gov Identifier: NCT05845229
• Other Study ID Numbers: REC/19/0096
• First Posted: May 6, 2023
• Last Update Posted: May 6, 2023
• Last Verified: May 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Ulster: Lipid mediators; Nutrient sensing,; Bioavailability,; N-acylethanolamines,; Satiety.

Study Results

No Results Posted as of May 6, 2023