Dietary Fibers and Satiety in Bariatric Patients
Condition: Bariatric Surgery Candidate
Study type: Interventional

Summary: 
      The primary objective is to evaluate the effect of a viscous and fermentable dietary fibre on
      ad libitum eating in morbidly obese patients before and 6 month after Roux-en-Y gastric
      bypass (RYGB) surgery.

      The secondary objectives are to study the effect of a viscous and fermentable dietary fibre
      on perceived appetite, the production of short chain fatty acids (SCFA), breath hydrogen (as
      a marker of large intestinal fermentation), the secretion of gastrointestinal (GI) satiation
      hormones and glycaemia in morbidly obese patients before and 6 month after RYGB surgery.

      The primary study outcome measure is macronutrient and food intake (grams and kcal eaten) at
      the ad libitum buffet meal as well as time to complete the meal.

      Secondary outcome measures are 1) Appetite ratings (validated visual analogue scales, VAS)
      including hunger, fullness, thirst, desire to eat, and amount of food desired to eat. 2)
      Plasma concentrations of SCFA (propionate, acetate, butyrate). 3) Breath hydrogen (as a
      marker of large intestinal fermentation) 4) Plasma concentrations of gastrointestinal
      hormones (ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY)
      and potentially other, yet to be identified gut hormones). 4) Concentrations of plasma
      insulin and glucagon and blood glucose.

      Randomized, single-blinded cross-over trial in 24 morbidly obese human subjects undergoing
      RYGB (study A, n=12; study B, n=12). Study B also includes an additional pilot study in 6
      morbidly obese patients before and 6 month after RYGB surgery. Thus, the total number of
      subjects including the pilot study is 30.
    

Detailed description: 
      Obesity has reached epidemic proportions worldwide. The only effective treatment option
      currently available is bariatric surgery, with the gold standard procedure, the Roux-en-Y
      gastric bypass (RYGB), resulting in dramatic and sustained excess weight loss of 60-75% and
      often prompt amelioration of type 2 diabetes mellitus (T2DM). The unparalleled efficacy of
      bariatric surgery in obesity treatment opens a completely new perspective for the development
      of anti-obesity drugs, and suggests that the gastrointestinal (GI) tract is of much more
      importance in the control of eating and energy homeostasis than previously thought.Two key GI
      mechanisms have been identified to inhibit eating: 1) gastric distention resulting in
      activation of mechanoreceptors and neural gut brain signaling, and 2) small intestinal
      nutrient sensing resulting in the secretion of satiation peptides such as CCK, GLP-1 and PYY.

      A completely novel implication of the importance of the GI tract in the control of eating and
      body weight is the role of the large intestine and the gut microbiome as well as its
      metabolic products.That the gut microbiome can have potent effects on eating and body weight
      was first recognized in landmark experiments with germ-free mice that became obese when they
      were inoculated with microbiota from obese mice or humans, while they remained lean when
      microbiota was transplanted from lean mice.

      The exact mechanisms that link the gut microbiome to the control of eating and energy
      homeostasis remain however, largely unexplored. One suggestion for obesity development is
      that the 'obese' microbiome may have an increased capacity to extract energy from the same
      diet as compared with a 'lean' microbiome. In fact, short chain fatty acids (SCFA) formed
      through bacterial fermentation of indigestible carbohydrates can provide additional energy to
      the host (about 10% of total energy from the diet). However, whether this is the main cause
      for obesity development remains controversial because SCFA also stimulate the secretion of
      leptin, GLP-1 and PYY and, thus, activate eating-inhibitory mechanisms. Because under
      physiological conditions, a meal will take about 6 hours or longer (depending on meal
      composition and inter-individual variability of intestinal transit) until it reaches the
      large intestine so that fermentable meal components can be metabolized to SCFA, the
      contribution of SCFA in acute eating-inhibitory effects has been questioned in humans.
      Bariatric patients provide an ideal model to study this mechanism. Based on the anatomical
      alterations during RYGB surgery resulting in a much faster nutrient transit to the large
      intestine, it can be hypothesized that a more rapid and more pronounced production of SCFA
      contributes to the marked acute eating-inhibitory effects as seen after surgery. In addition,
      RYGB patients have a small stomach pouch about 2% of the size of a normal, un-operated
      stomach resulting in early distention upon food ingestion. The effect of increased stomach
      distention and its contribution to the overall effects on eating behavior and weight loss
      have not been evaluated, to the best of our knowledge. Dietary fibres provide an ideal
      nutritional intervention to study the underlying eating-inhibitory effects of RYGB surgery.
      1) High viscous fibres such as oat beta glucan delay gastric emptying and, thus, may
      contribute to the eating effect via an increase in gastric distention. 2) Non-viscous,
      fermentable fibres such as inulin or fructo-oligossachides (FOS) are highly fermented into
      SCFA in the large intestine upon ingestion, and thus may participate in the eating effect via
      activation of SCFA receptors and release of satiation hormones.

      The primary objective in both study A and B is to evaluate the effect of a viscous and
      fermentable dietary fibre on ad libitum eating in morbidly obese patients before and 6 month
      after RYGB surgery.

      In addition, in the pilot study in study B, the primary objective is the time course of
      fibre-induced large intestinal fermentation.

      The secondary objectives in both study A and B are to study the effect of a viscous and
      fermentable dietary fibre on perceived appetite, the production of SCFA, breath hydrogen (as
      a marker of large intestinal fermentation), the secretion GI satiation hormones and glycaemia
      in morbidly obese patients before and 6 month after RYGB surgery.

      The primary study outcome measure in both study A and B is macronutrient and food intake
      (grams and kcal eaten) at the ad libitum buffet meal as well as time to complete the meal.

      In addition, in the pilot study in study B, the primary study outcome measure is breath
      hydrogen and plasma SCFA concentrations.

      Secondary outcome measures in both study A and B are 1) Appetite ratings (validated visual
      analogue scales, VAS) including hunger, fullness, thirst, desire to eat, and amount of food
      desired to eat. 2) Plasma concentrations of SCFA (propionate, acetate, butyrate). 3) Breath
      hydrogen (as a marker of large intestinal fermentation) 4) Plasma concentrations of
      gastrointestinal hormones (ghrelin, CCK, GLP-1, PYY and potentially other, yet to be
      identified gut hormones). 4) Concentrations of plasma insulin and glucagon and blood glucose.

      Randomized, single-blinded cross-over trial in 24 morbidly obese human subjects undergoing
      RYGB (study A, n=12; study B, n=12). Study B also includes an additional pilot study in 6
      morbidly obese patients before and 6 month after RYGB surgery. Thus, the total number of
      subjects including the pilot study is 30.
    

Intervention name(s): Fiber or Placebo (depending on the randomization)
Intervention type(s): Dietary Supplement
Intervention description(s): ingestion of dietary fibers prior to meal intake
Other intervention name(s): Placebo
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Randomized, single-blinded cross-over trial in 24 morbidly obese human subjects undergoing RYGB.
Masking: Single (Participant)
Primary purpose: Supportive Care