The Fructose and Allulose Catalytic Effects (FACE) Trial
Condition: Type 2 Diabetes
Study type: Interventional

Summary: 
      Diabetes remains one of the most important unmet prevention and treatment challenges, and the
      prevalence of diabetes continues to grow. Some functional food ingredients may hold promise
      as potential therapies for diabetes. One such functional food is allulose, which is a c-3
      epimer of fructose. Allulose is a non-caloric sugar found naturally in small amounts in foods
      such as dried fruits, brown sugar and maple syrup. Previous research has found that catalytic
      doses of fructose and allulose have been shown to decrease the postprandial glycemic
      responses to high glycemic index meals. Fructose, in exchange for other carbohydrates, has
      also been found to decrease HbA1c levels. Whether the effects of fructose and allulose are
      equivalent is of particular interest, as allulose represents a non-caloric alternative to
      fructose. The minimum 'catalytic' dose at which improvements in carbohydrate metabolism are
      observed also remains to be determined for each of the sugars in people with and without
      diabetes. This study is an acute randomized controlled dose-finding equivalence trial to
      assess the effect of fructose and allulose at 2 dose levels (5g and 10g) compared with
      control (0g) on the glucose and insulin responses to a 75g oral glucose tolerance test (OGTT)
      in healthy and type 2 diabetes participants.
    

Detailed description: 
      Diabetes remains one of the most important unmet prevention and treatment challenges. Despite
      the growing armamentarium of medications, which include six new classes of drugs since
      metformin was first approved in 1995 in the US, the combined prevalence of impaired glucose
      tolerance (IGT) and diabetes continues to grow. Although oral antihyperglycaemic agents have
      been shown to prevent the development of diabetes in high-risk individuals and to reduce the
      risk of microvascular complications in individuals with type 2 diabetes, they have failed to
      deliver the anticipated macrovascular benefits.

      Some functional food ingredients may hold promise as potential therapies for diabetes. An
      emerging literature has shown that low-dose fructose and its c-3 epimer, allulose (a
      non-caloric sugar found naturally in small amounts in foods such as dried fruits, brown
      sugar, and maple syrup which is generally recognized as safe [GRAS] by the FDA under GRN 400
      since 2012 and GRN 498 since 2014) may benefit glycemic control.

      Clinical translation of these findings has proven promising. Catalytic doses of fructose at
      7.5g and 10g and allulose at 5g, 7.5g, and 10g (but not 2.5g) have been shown to decrease the
      postprandial glycemic responses to high glycemic index meals (oral glucose, maltodextrins, or
      mashed potatoes) from ~15-30% in healthy participants and those with prediabetes or diabetes.
      These acute effects have been shown to be sustainable over the longer term in the case of
      fructose. In separate systematic reviews and meta-analyses of controlled feeding trials, the
      investigators showed that both small doses (defined as ≤36g/day based on 3 meals at ≤10g/meal
      and 2 snacks at ≤3g/snack) and higher doses (median, 60g/day) of fructose in exchange for
      other carbohydrates decreased HbA1c by 0.4% and 0.53%, respectively, a level of reduction
      which exceed the clinically meaningful threshold of 0.3% proposed by the Federal Drug
      Administration (FDA) for the development of new oral anti-hyperglycemic agents.

      Although these findings provide a compelling proof of concept, there is an urgent need for
      replication studies. Whether the effects of fructose and allulose are equivalent is of
      particular interest, as allulose represents a non-caloric alternative to fructose. The
      minimum 'catalytic' dose at which improvements in carbohydrate metabolism are observed also
      remains to be determined for each of the sugars in people with and without diabetes.

      OBJECTIVES

        -  To assess the acute catalytic effects of fructose and allulose at 2 dose levels (5g,
           10g) compared with control (0g) on glucose and insulin responses to a 75g oral glucose
           tolerance test (75g-OGTT) in healthy participants and participants with type 2 diabetes.

        -  To assess whether there is a dose response or threshold over the proposed dose range
           (0g, 5g, 10g) for the effects of fructose and allulose on glucose and insulin responses
           to a 75g-OGTT in healthy participants and participants with type 2 diabetes.

        -  To assess whether the effects of allulose and fructose are equivalent on the primary
           endpoint of incremental area under the curve (iAUC) for plasma glucose across the 2 dose
           levels (5g and 10g) compared with control (0g) in healthy participants and participants
           with type 2 diabetes.
    

Intervention name(s): Allulose; Fructose; Control
Intervention type(s): Other; Other; Other
Intervention description(s): A double-blind, randomized, multiple-crossover "equivalence" design. Each participant will act as their own control receiving the treatments in random order, each separated by a 1 week washout period. The treatment will be developed by Tate & Lyle.; A double-blind, randomized, multiple-crossover "equivalence" design. Each participant will act as their own control receiving the treatments in random order, each separated by a 1 week washout period. The treatment will be developed by Tate & Lyle.; A double-blind, randomized, multiple-crossover "equivalence" design. Each participant will act as their own control receiving the treatments in random order, each separated by a 1 week washout period. The treatment will be developed by Tate & Lyle.
Other intervention name(s): D-psicose
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: Allulose; Fructose; Dose Response; Catalytic Dose; Carbohydrate metabolism; Randomized clinical trials