Proof of Concept Study; The Effect of an Encapsulated Nutrient Mixture on Ileal Brake Activation

September 29, 2016 updated by: Maastricht University Medical Center

The Effect of an Encapsulated Nutrient Mixture on Ileal Brake Activation: A Double-blind Randomized Study to Investigate the Effects on Body Weight, Food Intake and Satiety.

Intraileal infusion of nutrients results in a reduction in food intake. A previous study by our group showed that both sucrose and casein infusion resulted in an increase in satiety and release of gastrointestinal peptides and a decrease in hunger and food intake. Encapsulating both nutrients, daily ingestion of this micro encapsulate and hereby releasing them in the distal small intestine could result in a chronic ileal brake activation. The obtained reduction in food intake and caloric intake could help overweight subjects to lose weight.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Obesity and weight management Worldwide the incidence of overweight and obesity is rapidly increasing with negative impact on health and health care costs. The efficacy of the currently available treatments is relatively limited on the long term. So far, surgical intervention has been proven to be the only strategy to overcome severe obesity in the long-term. Furthermore, in a recent meta-analysis it was concluded that dietary supplements and exercise alone does not contribute to improved weight loss after caloric restriction diets. Therefore, it is important to develop new effective strategies that induce weight loss or help weight maintenance after weight loss. A promising mechanism for weight management is to activate the so called 'ileal brake'. Ileal brake The ileal brake refers to an intestinal feedback mechanism that is triggered by nutrients at a specific location in the small intestine, resulting not only in modulation of gastrointestinal secretions and motility but also of food intake and hunger. The ileal brake can be activated by ileal infusion of undigested lipid and recently it was found that ileal infusion of sucrose and casein suppresses food intake to the same extend as equicaloric amount of lipids8. In addition to the reduction of food intake, an increase in feelings of satiety and decrease in hunger was found. Since ileal brake activation seems to be a promising target for weight management strategies alternative nutrient delivery techniques have to be used. Several studies investigated the effects of nutrient infusion in all regions of the small intestine. However all studies used intestinal feeding catheters in order to infuse nutrients directly into the desired part of the small intestine. In order to investigate the effect of long-term ileal brake activation in overweight individuals, a different approach for nutrient delivery needs to be chosen. An alternative for distal small intestinal nutrient delivery via feeding catheters is encapsulation of nutrients. Encapsulation can be used to deliver nutrients to a specific intestinal location. By encapsulation, nutrients are covered/surrounded with an edible coating. This coating is defined as a thin layer of edible material applied to the surface of the nutrients. This provides a barrier against digestion in the stomach and the proximal parts of the small intestine. Comparable approaches have already been used for site-specific drug delivery. Two examples of systems able to deliver drugs to the ileo-colonic region are the ColoPulse system described by Schellekens et al. (2010) and the ileo-colonic delivery system described by Varum et al. (2013). Both methods are invented to accelerate drug release in the ileo-colonic region and use specific Eudragit® polymer coatings. Adjusting these polymer coatings results in a more proximal (ileum) delivery. However these techniques were developed for drug delivery. To activate the ileal brake it is preferred to use a completely food grade application. Another food grade approach to deliver nutrients to the distal small intestine is micro-encapsulation. This micro-encapsulation technique will be used in the present study to deliver a mixture of nutrients consisting mostly sucrose (60%) , casein (30%) in a shell of whey protein (10%) to the distal small intestine. The delivery method patented by AnaBio Technologies Ltd. (http://www.AnaBio.ie/) comprises an active component, encapsulated within a protein matrix of preferably whey protein. The mechanism by which their technique delivers the active to the preferred intestinal location is based on pH, surface porosity of the microspheres, and reaction to specific enzymes. These three parameters are used to design the micro-encapsulation beads to deliver the active ingredient to the preferred intestinal location (e.g. duodenum, jejunum or ileum). Furthermore the size of the micro-beads is important for intestinal transit time. AnaBio uses their data collected from human and animal studies to relate the size of the micro-beads to intestinal transit time, dose volume and physiological characteristics. The micro-bead size (micron range) can be chosen based on the population group and the required transit time, an average used size is 150 micron. The advantage of these small particles is that the particles can be mixed with a food product. The ratio active : encapsulated protein matrix is 95 : 5%. This means that if sucrose will be encapsulated 95% of the micro-bead is pure sucrose and 5% is whey protein. We know from our previous research8 that infusion with 13 grams of sucrose is able to activate the ileal brake. For the present study we will use a mixture of encapsulated sucrose microbeats (60%) and encapsulated casein microbeats (30%) in order to simulate the composition of a small mixed carbohydrate and protein rich meal. Efficacy small intestinal delivery AnaBio provided data (which cannot be shared due to IP applications) of four in vivo studies of which 3 were human studies and 1 pig study. In these studies the efficacy of their delivery method has been investigated. It can be concluded from these studies that the whey protein micro-encapsulation technique is a specific intestinal delivery method for specific to either the ileum (2 human studies and 1 pig study) or the jejunum (1 human study). Present study In the present study the effect of 6 weeks ileal brake activation on body weight, BMI and waist circumference will be investigated. It is hypothesized that 6 weeks ileal brake activation by delivery of an encapsulated nutrient mixture to the distal small intestine results in reduced body weight. This will be studied by daily ingestion of an encapsulated nutrient mixture (e.g. 60% sucrose and 30% casein encapsulated in 10% whey protein) either delivered to the distal small intestine (active) or stomach (placebo) before lunch and dinner for 6 weeks in a randomized, double blind parallel placebo controlled trial. This will be studied in the second phase of the study (phase 2). Pre intervention, study day 1 and 2 (SD1 and SD2), middle (SD4) and post (SD5) intervention period the efficacy of the to decrease food intake (>68 kcal) will be evaluated. It is unknown whether the ileal brake will be activated by the encapsulated nutrient mixture delivered to the distal small intestine (active) to the same magnitude as ileal brake activation by ileal sucrose and casein infusion. Therefore, we will study the ileal brake activation efficacy of the encapsulated nutrient mixture ingestion on ad libitum food intake. This will be done in the first phase of the study (phase 1). Pre-intervention the efficacy will be tested in a randomized placebo controlled cross over design. Within every subject the difference in ad libitum food intake after active or placebo ingestion will be studied. If the active encapsulated nutrient mixture does not result in a reduction of food intake the intervention will not start.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
62

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Limburg
      • Maastricht, Limburg, Netherlands, 6229 HX
        • Maastricht University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Based on medical history and previous examination, no gastrointestinal complaints can be defined.
  • Age between 18 and 65 years. A higher age comes with a higher chance of comorbidities. These could influence our study outcomes and therefore this age range was chosen. This study will include healthy adult subjects (male and female). Women must be taking contraceptives (only needed in women with childbearing potential)
  • BMI between 25 -30 kg/m2
  • Normal Dutch eating habits eating three meals a day including breakfast as assessed by a validated questionnaire
  • Voluntary participation
  • Able to participate in the study, willing to give informed consent and to comply with the study procedures and restrictions

Exclusion Criteria:

  • History of severe cardiovascular, respiratory, urogenital, gastrointestinal/ hepatic, hematological/immunologic, HEENT (head, ears, eyes, nose, throat), dermatological/connective tissue, musculoskeletal, metabolic/nutritional, endocrine, neurological/psychiatric diseases, allergy, major surgery and/or laboratory assessments which might limit participation in or completion of the study protocol. The severity of the disease (major interference with the execution of the experiment or potential influence on the study outcomes) will be decided and documented by the principal investigator.
  • Use of any medication, except oral contraceptives, which may interfere with this study (major interference with the execution of the experiment or potential influence on the study outcomes). This has to be decided and documented by the principle investigator.
  • Administration of investigational drugs or participation in any scientific intervention study which may interfere with this study, to be decided by the principle investigator, in the 90 days prior to the study.
  • Major abdominal surgery interfering with gastrointestinal function (uncomplicated appendectomy, cholecystectomy and hysterectomy allowed, and other surgery) upon judgement of the principle investigator.
  • Dieting (medically prescribed, diabetic and vegetarian)
  • Pregnancy, lactation
  • Excessive alcohol consumption (>20 alcoholic consumptions per week)
  • Intention to stop smoking
  • Self-admitted HIV-positive state
  • Above average score (>2.26) on the restrained eating scale of the Dutch Eating Behaviour Questionnaire
  • Reported unexplained weight loss or gain of >4 kg in the month prior to screening

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Encapsulated nutrients
The investigational product will be a shot of sterile water (80 ml) mixed with a total of 21.6 grams encapsulate consisting of 13 grams of sucrose (60% of the total) encapsulated whey protein (<5% of total). On top of the encapsulated sucrose, 6.44 grams of casein (30% of total) encapsulated in whey protein (<5% of total) will be mixed with the shot of water. The micro-beats of encapsulated sucrose and casein are 150 µm and the ratio active (sucrose and casein) : whey is 95:5%, this means that the shot of water contains 13 grams of encapsulated sucrose, 6.44 grams of encapsulated casein and 1.3 grams of whey protein required for the encapsulation.
Other: Encapsulated nutrients
Placebo Comparator: Placebo
The placebo has the same nutrient composition (e.g. 13 grams of sucrose and 6.44 grams of casein) as the active and will be equicaloric, and will also be mixed with a shot of sterile water (80 ml). The main difference of the placebo is that this nutrient mixture will be immediately released in the stomach, instead of being delivered to the ileum (active). This immediate release of the nutrient mixture is possible by using a different micro-encapsulation technique.
Other: Placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Ileal brake activation and weight loss.
Time Frame: 43 days (measuring outcome at T=23 days and T=43 days)
The difference in body weight before and after 6 weeks ileal brake activation by nutrient delivery to the distal small intestine (active; group 1) compared to nutrient mixture delivery to the stomach (placebo; group 2).
43 days (measuring outcome at T=23 days and T=43 days)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Ileal brake and food intake.
Time Frame: 43 days (measuring outcome at T=23 days and T=43 days)
To investigate whether intake of encapsulated nutrient mixture delivered in the distal small intestine (active) decreases the amount of food consumed during a subsequent ad libitum meal compared to encapsulated nutrient mixture delivered in the stomach (placebo) in time, analysed pre-, middle and post intervention.
43 days (measuring outcome at T=23 days and T=43 days)
Ileal brake and VAS scores.
Time Frame: 43 days (measuring outcome at T=23 days and T=43 days)
To investigate whether intake of encapsulated nutrient mixture (active) increases satiation analysed by VAS-scores compared to placebo pre, middle and post intervention.
43 days (measuring outcome at T=23 days and T=43 days)

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Ileal brake and plasma GLP-1 level
Time Frame: 43 days (measuring outcome at T=23 days and T=43 days)
To evaluate effects of 6 weeks encapsulated nutrient delivery to the distal small intestine (active) on GLP-1 plasma concentration compared to nutrient delivery to the stomach (placebo). This will be analysed by monitor blood glucose and insulin responses in time pre- and post-intervention.
43 days (measuring outcome at T=23 days and T=43 days)
Ileal brake and plasma glucose level
Time Frame: 43 days (measuring outcome at T=23 days and T=43 days)
To evaluate effects of 6 weeks encapsulated nutrient delivery to the distal small intestine (active) on glucose plasma concentration compared to nutrient delivery to the stomach (placebo). This will be analysed by monitor blood glucose and insulin responses in time pre- and post-intervention.
43 days (measuring outcome at T=23 days and T=43 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Maastricht University Medical Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: A.A.M. Masclee, MD, PhD, Maastricht University Medical Center (MUMC+)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 14, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 16, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 21, 2015

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 30, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 29, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • METC 143062

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