Laxative Properties of Microencapsulated Lipid (Constipation Study)

A Proof of Principle Study of the Laxative Properties of Microencapsulated Lipid in Patients Experiencing Constipation Related to Intentional Weight Loss

The present study seeks to build on these observations to assess whether in principle, fat containing microcapsules might help patients experiencing constipation in association with weight loss interventions (including GLP-1 analogues or bariatric surgery) to both avoid/treat constipation and simultaneously optimise their ability to feel full during eating. This potential dual action may provide added benefit versus the use of traditional approaches to constipation prophylaxis e.g., lactulose.

Study Overview

• Status: Recruiting
• Conditions: Constipation
• Intervention / Treatment: Dietary supplement: Fat Microcapsules

Detailed Description

Chronic constipation most frequently arises as a functional disorder of at least 3 months duration, the aetiology of which is multifactorial encompassing dietary and lifestyle factors arising in the context of intact colonic motility. Confirmatory clinical diagnosis of chronic constipation under this definition can be made with reference to the Rome IV criteria encompassing assessment of stool frequency, quality, straining etc.

Whilst broadly prevalent across the population, constipation is particularly troublesome in a significant number of patients undergoing interventions for weight loss in obesity, be that dietary, pharmacological or surgical. Calorie restriction per se, which is a common feature of most interventions for obesity necessarily reduces stimulation of colonic motility by impacting the frequency and intensity of colonic mass movements. Moreover, decreases in dietary fibre during food restriction result in debulking of the stool.

Multiple dietary and pharmacological approaches to the management of chronic constipation are available to mitigate the risk of constipation during weight loss and treat it when it becomes manifest. However, these can often be poorly accepted due to gastrointestinal side effects. Interestingly, the potential laxative properties of orlistat, a pancreatic lipase inhibitor-based treatment for morbid obesity have been investigated in off-label studies in the setting of idiopathic chronic constipation and constipation associated with opioid pain medication and anti-psychotic (clozapine) therapy. Mechanism of action in these cases most probably relates to the pro-kinetic and lubricatory effects of the increasing passage of undigested fat to the colon. Based on these case series, the potential for weight loss pharmacotherapy with in-built mitigation of associated constipation becomes an attractive concept.

When digestive and absorptive processes are impeded or moved distally in the small intestine, as can happen with respect to dietary triglycerides during orlistat therapy, satiety gut hormone signal and quantity of food intake are affected. During an ileal infusion of a lipid emulsion, healthy subjects ate a smaller amount compared to control infusions. A study in healthy volunteers in which fat was delivered via a nasal tube to the duodenum, jejunum and ileum found that the ileal treatment had the most pronounced effect on food intake and satiety.

The investigators have used a new food encapsulation technology using natural food grade pea protein, AnaBio©*, to deliver pure oleic acid to the distal small intestine showed significant attenuation of food intake in association with enhancement of enteroendocrine satiety hormone release. The results recorded an increase in the number of bowel motions over the subsequent 24 hours in half of the participants. Subsequently, the investigators showed that ingestion of a smaller 400kcal cargo of microencapsulated oleic acid resulted in decreased hunger and food intake, no increase in the frequency of bowel motion but an increase in stool softness.

Based on the above data the investigators are encouraged to proceed with the present study, the main goal of which is therefore to investigate whether the 400kcal dose of encapsulated fat delivered to the distal small intestine might be a useful supportive therapy in patients engaged in intensive weight loss therapies and experiencing constipation as a consequence.

• Study Type: Interventional
• Enrollment (Anticipated): 31
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Carel le Roux; Phone Number: +353864117842; Email: carel.leroux@ucd.ie

Study Locations

• Ireland
  • Dublin, Ireland, Dublin 4
    • Recruiting
    • Clinical Research Centre
    • Contact: Carel le Roux; Phone Number: +353864117842; Email: carel.leroux@ucd.ie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18-65 years
• Engaged in weight loss treatment
• Diagnosis of chronic constipation (Rome IV criteria)1
• Capacity to consent to participate

Exclusion Criteria:

• Substance abuse
• Pregnancy
• Patients who are taking medication for constipation should be on stable doses of medications for constipation for more than 2 weeks. They should neither start nor stop any medication for constipation in the 2 weeks prior to the visits.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Microencapsulated fat stomach; Participants will consume a drink containing 400kcal of microencapsulated fat that will be released in the stomach.	Dietary supplement: Fat Microcapsules; Consumption of a drink that contains microencapsulated fat that will be released either in the stomach or in the distal small intestines.
Experimental: Microencapsulated fat intestine; Participants will consume a drink containing 400kcal of microencapsulated fat that will be released in the intestine.	Dietary supplement: Fat Microcapsules; Consumption of a drink that contains microencapsulated fat that will be released either in the stomach or in the distal small intestines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Completed bowel motion	Proportion of participants reporting a completed bowel motion within 24 hours.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hunger	Hunger scores as measured by Visual Analogue Scales, the scale has a score from 0 to 100 with 0 being least hungry and 100 being most hungry.	6 hours
calories	Number of calories consumed during an ad libitum meal	6 hours
Gut hormones	Gut hormones concentration	6 hours
Fullness	Fullness scores as measured by Visual Analogue Scales, the scale has a score from 0 to 100 with 0 being least full and 100 being most full	6 hours

Collaborators and Investigators

• Sponsor: University College Dublin
• Investigators: Principal Investigator: Carel le Roux, University College Dublin

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2022
• Primary Completion (Anticipated): April 15, 2023
• Study Completion (Anticipated): April 15, 2023

Study Registration Dates

• First Submitted: April 4, 2022
• First Submitted That Met QC Criteria: April 4, 2022
• First Posted (Actual): April 12, 2022

Study Record Updates

• Last Update Posted (Actual): May 31, 2022
• Last Update Submitted That Met QC Criteria: May 25, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation
• Other Study ID Numbers: RS21-058

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