NCT02459834

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at P25-P50 for not_applicable type-2-diabetes

Timeline
Completed

Started Nov 2015

Shorter than P25 for not_applicable type-2-diabetes

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 21, 2015

Completed
12 days until next milestone

First Posted

Study publicly available on registry

June 2, 2015

Completed
5 months until next milestone

Study Start

First participant enrolled

November 1, 2015

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2016

Completed
Last Updated

August 8, 2017

Status Verified

August 1, 2017

Enrollment Period

9 months

First QC Date

May 21, 2015

Last Update Submit

August 4, 2017

Conditions

Type 2 Diabetes

Keywords

AlluloseFructoseDose ResponseCatalytic DoseCarbohydrate metabolismRandomized clinical trials

Outcome Measures

Primary Outcomes (1)

  • Plasma glucose iAUC

    up to 12 weeks

Secondary Outcomes (10)

  • Plasma glucose total AUC

    up to 12 weeks

  • Plasma insulin iAUC

    up to 12 weeks

  • Plasma insulin total AUC

    up to 12 weeks

  • Maximum concentrations (Cmax) for plasma glucose and insulin

    up to 12 weeks

  • Time of maximum concentrations (Tmax) for plasma glucose and insulin

    up to 12 weeks

  • +5 more secondary outcomes

Study Arms (3)

Allulose + 75g OGTT

EXPERIMENTAL

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

Fructose + 75g OGTT

EXPERIMENTAL

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

75g OGTT (Control)

ACTIVE COMPARATOR

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

Interventions

AlluloseOTHER

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.

Also known as: D-psicose
Allulose + 75g OGTT
FructoseOTHER

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.

Fructose + 75g OGTT
ControlOTHER

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.

75g OGTT (Control)

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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)
  • +41 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

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, M5C 2T2, Canada

Location

Related Publications (15)

  • Sievenpiper JL, de Souza RJ, Cozma AI, Chiavaroli L, Ha V, Mirrahimi A. Fructose vs. glucose and metabolism: do the metabolic differences matter? Curr Opin Lipidol. 2014 Feb;25(1):8-19. doi: 10.1097/MOL.0000000000000042.

    PMID: 24370846BACKGROUND

  • Cozma AI, Sievenpiper JL, de Souza RJ, Chiavaroli L, Ha V, Wang DD, Mirrahimi A, Yu ME, Carleton AJ, Di Buono M, Jenkins AL, Leiter LA, Wolever TM, Beyene J, Kendall CW, Jenkins DJ. Effect of fructose on glycemic control in diabetes: a systematic review and meta-analysis of controlled feeding trials. Diabetes Care. 2012 Jul;35(7):1611-20. doi: 10.2337/dc12-0073.

    PMID: 22723585BACKGROUND

  • Sievenpiper JL, Chiavaroli L, de Souza RJ, Mirrahimi A, Cozma AI, Ha V, Wang DD, Yu ME, Carleton AJ, Beyene J, Di Buono M, Jenkins AL, Leiter LA, Wolever TM, Kendall CW, Jenkins DJ. 'Catalytic' doses of fructose may benefit glycaemic control without harming cardiometabolic risk factors: a small meta-analysis of randomised controlled feeding trials. Br J Nutr. 2012 Aug;108(3):418-23. doi: 10.1017/S000711451200013X. Epub 2012 Feb 21.

    PMID: 22354959BACKGROUND

  • Agius L, Peak M. Intracellular binding of glucokinase in hepatocytes and translocation by glucose, fructose and insulin. Biochem J. 1993 Dec 15;296 ( Pt 3)(Pt 3):785-96. doi: 10.1042/bj2960785.

    PMID: 8280078BACKGROUND

  • Van Schaftingen E, Detheux M, Veiga da Cunha M. Short-term control of glucokinase activity: role of a regulatory protein. FASEB J. 1994 Apr 1;8(6):414-9. doi: 10.1096/fasebj.8.6.8168691.

    PMID: 8168691BACKGROUND

  • Hossain MA, Kitagaki S, Nakano D, Nishiyama A, Funamoto Y, Matsunaga T, Tsukamoto I, Yamaguchi F, Kamitori K, Dong Y, Hirata Y, Murao K, Toyoda Y, Tokuda M. Rare sugar D-psicose improves insulin sensitivity and glucose tolerance in type 2 diabetes Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Biochem Biophys Res Commun. 2011 Feb 4;405(1):7-12. doi: 10.1016/j.bbrc.2010.12.091. Epub 2010 Dec 25.

    PMID: 21187061BACKGROUND

  • Shiota M, Moore MC, Galassetti P, Monohan M, Neal DW, Shulman GI, Cherrington AD. Inclusion of low amounts of fructose with an intraduodenal glucose load markedly reduces postprandial hyperglycemia and hyperinsulinemia in the conscious dog. Diabetes. 2002 Feb;51(2):469-78. doi: 10.2337/diabetes.51.2.469.

    PMID: 11812757BACKGROUND

  • Hawkins M, Gabriely I, Wozniak R, Vilcu C, Shamoon H, Rossetti L. Fructose improves the ability of hyperglycemia per se to regulate glucose production in type 2 diabetes. Diabetes. 2002 Mar;51(3):606-14. doi: 10.2337/diabetes.51.3.606.

    PMID: 11872657BACKGROUND

  • Petersen KF, Laurent D, Yu C, Cline GW, Shulman GI. Stimulating effects of low-dose fructose on insulin-stimulated hepatic glycogen synthesis in humans. Diabetes. 2001 Jun;50(6):1263-8. doi: 10.2337/diabetes.50.6.1263.

    PMID: 11375325BACKGROUND

  • Moore MC, Cherrington AD, Mann SL, Davis SN. Acute fructose administration decreases the glycemic response to an oral glucose tolerance test in normal adults. J Clin Endocrinol Metab. 2000 Dec;85(12):4515-9. doi: 10.1210/jcem.85.12.7053.

    PMID: 11134101BACKGROUND

  • Heacock PM, Hertzler SR, Wolf BW. Fructose prefeeding reduces the glycemic response to a high-glycemic index, starchy food in humans. J Nutr. 2002 Sep;132(9):2601-4. doi: 10.1093/jn/132.9.2601.

    PMID: 12221216BACKGROUND

  • Iida T, Kishimoto Y, Yoshikawa Y, Hayashi N, Okuma K, Tohi M, Yagi K, Matsuo T, Izumori K. Acute D-psicose administration decreases the glycemic responses to an oral maltodextrin tolerance test in normal adults. J Nutr Sci Vitaminol (Tokyo). 2008 Dec;54(6):511-4. doi: 10.3177/jnsv.54.511.

    PMID: 19155592BACKGROUND

  • Hayashi N, Iida T, Yamada T, Okuma K, Takehara I, Yamamoto T, Yamada K, Tokuda M. Study on the postprandial blood glucose suppression effect of D-psicose in borderline diabetes and the safety of long-term ingestion by normal human subjects. Biosci Biotechnol Biochem. 2010;74(3):510-9. doi: 10.1271/bbb.90707. Epub 2010 Mar 7.

    PMID: 20208358BACKGROUND

  • Moore MC, Davis SN, Mann SL, Cherrington AD. Acute fructose administration improves oral glucose tolerance in adults with type 2 diabetes. Diabetes Care. 2001 Nov;24(11):1882-7. doi: 10.2337/diacare.24.11.1882.

    PMID: 11679451BACKGROUND

  • Braunstein CR, Noronha JC, Glenn AJ, Viguiliouk E, Noseworthy R, Khan TA, Au-Yeung F, Blanco Mejia S, Wolever TMS, Josse RG, Kendall CWC, Sievenpiper JL. A Double-Blind, Randomized Controlled, Acute Feeding Equivalence Trial of Small, Catalytic Doses of Fructose and Allulose on Postprandial Blood Glucose Metabolism in Healthy Participants: The Fructose and Allulose Catalytic Effects (FACE) Trial. Nutrients. 2018 Jun 9;10(6):750. doi: 10.3390/nu10060750.

    PMID: 29890724DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

psicoseFructose

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

HexosesMonosaccharidesSugarsCarbohydratesKetoses

Study Officials

  • John L Sievenpiper, MD PhD FRCPC

    University of Toronto

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
OTHER
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor

Study Record Dates

First Submitted

May 21, 2015

First Posted

June 2, 2015

Study Start

November 1, 2015

Primary Completion

August 1, 2016

Study Completion

August 1, 2016

Last Updated

August 8, 2017

Record last verified: 2017-08

Locations

CA(1)