Proof of Concept Study; The Effect of an Encapsulated Nutrient Mixture on Ileal Brake Activation
Condition: Body Weight Decreased
MeSH terms: Body Weight
Study type: Interventional

Summary: 
      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.
    

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.
    

Intervention name(s): Encapsulated nutrients; Placebo
Intervention type(s): Other; Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: food intake, satiety, satiation, nutrients, ileal brake