The Fructose and Allulose Catalytic Effects (FACE) Trial

August 4, 2017 updated by: John Sievenpiper, University of Toronto

An Acute Randomized Dose-finding Equivalence Trial of Small, Catalytic Doses of Fructose and Allulose on Postprandial Carbohydrate Metabolism: The Fructose and Allulose Catalytic Effects (FACE) Study

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • 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

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5C 2T2
        • The Toronto 3D (Diet, Digestive tract and Disease) Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital

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

Ages Eligible for Study

14 years to 71 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Healthy participants:

    • Adult males and non-pregnant females
    • Normal weight
    • Non-smokers
    • Free of any disease or illness
    • Do not regular take any medications
    • Have a primary care physician

  • Diabetes participants:

    • Well-controlled diabetes on diet and/or oral antihyperglycemic agents
    • Not taking insulin
    • Free of any major illness
    • Have a primary care physician

Exclusion Criteria:

  • Healthy participants:

    • Age <18 or >75y, Pregnant female
    • Regular medication use
    • Complementary or alternative medicine (CAM) use
    • BMI<18.5kg/m2, >30kg/m2
    • Prediabetes or diabetes (HbA1c≥6%, FBG≥6.1mmol/L)
    • Hypertension (BP≥140/90), Dyslipidemia (Canadian Cardiovascular Society guidelines)
    • Metabolic syndrome (harmonized definition)
    • Polycystic ovarian syndrome
    • Cardiovascular disease
    • Gastrointestinal disease
    • Previous bariatric surgery
    • Liver disease (abnormal liver enzymes)
    • Hyperthyroidism (abnormal TSH)
    • Hypothyroidism (abnormal TSH)
    • Nephropathy (albumin-to-creatinine ratio [ACR] >20)
    • Chronic kidney disease (eGFR >60ml/min/1.73m2)
    • Inflammatory conditions (CRP>3g/L)
    • Acute or chronic infection (abnormal white blood cell count (WBC), CRP>3g/L)
    • Anemia (abnormal Hb)
    • Lung disease
    • Cancer/malignancy
    • Psychiatric illness
    • Major surgery in the last 6 months
    • Other major illness
    • Smoker
    • Heavy alcohol use (>3 drinks/day)

  • Diabetes participants:

    • Age <18 or >75y
    • Pregnant female
    • Poorly controlled diabetes (HbA1c>7.5%)
    • Recent diabetes medication change (< 3 months)
    • Insulin use
    • Complementary or alternative medicine (CAM) use
    • BMI<18.5kg/m2, ≥35kg/m2
    • Cardiovascular disease
    • Retinopathy
    • Neuropathy
    • Diabetic foot
    • Gastrointestinal disease
    • Previous bariatric surgery
    • Liver disease (abnormal liver enzymes)
    • Hyperthyroidism (abnormal TSH)
    • Hypothyroidism (abnormal TSH)
    • Anemia (abnormal Hb)
    • Nephropathy (albumin-to-creatinine ratio [ACR] >20)
    • Chronic kidney disease (eGFR >60ml/min/1.73m2)
    • Inflammatory conditions (CRP>3g/L)
    • Acute or chronic infection (abnormal WBC, CRP>3g/L)
    • Lung disease
    • Cancer/malignancy
    • Psychiatric illness
    • Major surgery in the last 6 months
    • Other major illness
    • Smoker
    • Heavy alcohol use (>3 drinks/day)

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: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Allulose + 75g OGTT
Allulose added to a 75 g OGTT of 500 mL at 2 doses (5g and 10g). The drinks will be matched as much as possible in appearance, taste (sweetness), texture, and packaging.
Other: Allulose
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 Names:
  • D-psicose
Experimental: Fructose + 75g OGTT
Fructose added to a 75 g OGTT of 500 mL at 2 doses (5g and 10g). The drinks will be matched as much as possible in appearance, taste (sweetness), texture, and packaging.
Other: Fructose
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.
Active Comparator: 75g OGTT (Control)
A 75 g OGTT (alone) of 500 mL will be given to each participant. The drinks will be matched as much as possible in appearance, taste (sweetness), texture, and packaging.
Other: Control
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Plasma glucose iAUC
Time Frame: up to 12 weeks
up to 12 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Plasma glucose total AUC
Time Frame: up to 12 weeks
up to 12 weeks
Plasma insulin iAUC
Time Frame: up to 12 weeks
up to 12 weeks
Plasma insulin total AUC
Time Frame: up to 12 weeks
up to 12 weeks
Maximum concentrations (Cmax) for plasma glucose and insulin
Time Frame: up to 12 weeks
up to 12 weeks
Time of maximum concentrations (Tmax) for plasma glucose and insulin
Time Frame: up to 12 weeks
up to 12 weeks
Matsuda whole body insulin sensitivity index (Matsuda ISI OGTT);
Time Frame: up to 12 weeks
up to 12 weeks
Early insulin secretion index (∆PI30-0/∆PG30-0);
Time Frame: up to 12 weeks
up to 12 weeks
Insulin secretion-sensitivity index-2 (ISSI-2)
Time Frame: up to 12 weeks
up to 12 weeks
Mean incremental plasma glucose and insulin responses
Time Frame: up to 12 weeks
up to 12 weeks
Mean plasma glucose and insulin responses
Time Frame: up to 12 weeks
up to 12 weeks

Collaborators and Investigators

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

Sponsor

University of Toronto

Collaborators

Tate & Lyle

Investigators

  • Principal Investigator: John L Sievenpiper, MD PhD FRCPC, University of Toronto

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

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

November 1, 2015

Primary Completion (Actual)

August 1, 2016

Study Completion (Actual)

August 1, 2016

Study Registration Dates

First Submitted

May 21, 2015

First Submitted That Met QC Criteria

June 1, 2015

First Posted (Estimate)

June 2, 2015

Study Record Updates

Last Update Posted (Actual)

August 8, 2017

Last Update Submitted That Met QC Criteria

August 4, 2017

Last Verified

August 1, 2017

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • UT-FACE 2015

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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