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The Fructose and Allulose Catalytic Effects (FACE) Trial

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ClinicalTrials.gov Identifier: NCT02459834
Recruitment Status : Completed
First Posted : June 2, 2015
Last Update Posted : August 8, 2017
Sponsor:
Collaborator:
Tate & Lyle
Information provided by (Responsible Party):
John Sievenpiper, University of Toronto

Brief 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.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Other: Allulose Other: Fructose Other: Control Not Applicable

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  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Official Title: 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
Study Start Date : November 2015
Actual Primary Completion Date : August 2016
Actual Study Completion Date : August 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Fructose

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 Name: 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.




Primary Outcome Measures :
  1. Plasma glucose iAUC [ Time Frame: up to 12 weeks ]

Secondary Outcome Measures :
  1. Plasma glucose total AUC [ Time Frame: up to 12 weeks ]
  2. Plasma insulin iAUC [ Time Frame: up to 12 weeks ]
  3. Plasma insulin total AUC [ Time Frame: up to 12 weeks ]
  4. Maximum concentrations (Cmax) for plasma glucose and insulin [ Time Frame: up to 12 weeks ]
  5. Time of maximum concentrations (Tmax) for plasma glucose and insulin [ Time Frame: up to 12 weeks ]
  6. Matsuda whole body insulin sensitivity index (Matsuda ISI OGTT); [ Time Frame: up to 12 weeks ]
  7. Early insulin secretion index (∆PI30-0/∆PG30-0); [ Time Frame: up to 12 weeks ]
  8. Insulin secretion-sensitivity index-2 (ISSI-2) [ Time Frame: up to 12 weeks ]
  9. Mean incremental plasma glucose and insulin responses [ Time Frame: up to 12 weeks ]
  10. Mean plasma glucose and insulin responses [ Time Frame: up to 12 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02459834


Locations
Canada, Ontario
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
Toronto, Ontario, Canada, M5C 2T2
Sponsors and Collaborators
University of Toronto
Tate & Lyle
Investigators
Principal Investigator: John L Sievenpiper, MD PhD FRCPC University of Toronto

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: John Sievenpiper, Associate Professor, University of Toronto
ClinicalTrials.gov Identifier: NCT02459834     History of Changes
Other Study ID Numbers: UT-FACE 2015
First Posted: June 2, 2015    Key Record Dates
Last Update Posted: August 8, 2017
Last Verified: August 2017

Keywords provided by John Sievenpiper, University of Toronto:
Allulose
Fructose
Dose Response
Catalytic Dose
Carbohydrate metabolism
Randomized clinical trials