Ignite Creation Date:
2025-12-25 @ 2:32 AM
Ignite Modification Date:
2026-02-26 @ 6:24 AM
Study NCT ID:
NCT02459834
Status:
COMPLETED
Last Update Posted:
2017-08-08
First Post:
2015-05-21
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
The Fructose and Allulose Catalytic Effects (FACE) Trial
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003924', 'term': 'Diabetes Mellitus, Type 2'}], 'ancestors': [{'id': 'D003920', 'term': 'Diabetes Mellitus'}, {'id': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C003243', 'term': 'psicose'}, {'id': 'D005632', 'term': 'Fructose'}], 'ancestors': [{'id': 'D006601', 'term': 'Hexoses'}, {'id': 'D009005', 'term': 'Monosaccharides'}, {'id': 'D000073893', 'term': 'Sugars'}, {'id': 'D002241', 'term': 'Carbohydrates'}, {'id': 'D007661', 'term': 'Ketoses'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'OTHER', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 50}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2015-11'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2017-08', 'completionDateStruct': {'date': '2016-08', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2017-08-04', 'studyFirstSubmitDate': '2015-05-21', 'studyFirstSubmitQcDate': '2015-06-01', 'lastUpdatePostDateStruct': {'date': '2017-08-08', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2015-06-02', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2016-08', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Plasma glucose iAUC', 'timeFrame': 'up to 12 weeks'}], 'secondaryOutcomes': [{'measure': 'Plasma glucose total AUC', 'timeFrame': 'up to 12 weeks'}, {'measure': 'Plasma insulin iAUC', 'timeFrame': 'up to 12 weeks'}, {'measure': 'Plasma insulin total AUC', 'timeFrame': 'up to 12 weeks'}, {'measure': 'Maximum concentrations (Cmax) for plasma glucose and insulin', 'timeFrame': 'up to 12 weeks'}, {'measure': 'Time of maximum concentrations (Tmax) for plasma glucose and insulin', 'timeFrame': 'up to 12 weeks'}, {'measure': 'Matsuda whole body insulin sensitivity index (Matsuda ISI OGTT);', 'timeFrame': 'up to 12 weeks'}, {'measure': 'Early insulin secretion index (∆PI30-0/∆PG30-0);', 'timeFrame': 'up to 12 weeks'}, {'measure': 'Insulin secretion-sensitivity index-2 (ISSI-2)', 'timeFrame': 'up to 12 weeks'}, {'measure': 'Mean incremental plasma glucose and insulin responses', 'timeFrame': 'up to 12 weeks'}, {'measure': 'Mean plasma glucose and insulin responses', 'timeFrame': 'up to 12 weeks'}]}, 'conditionsModule': {'keywords': ['Allulose', 'Fructose', 'Dose Response', 'Catalytic Dose', 'Carbohydrate metabolism', 'Randomized clinical trials'], 'conditions': ['Type 2 Diabetes']}, 'referencesModule': {'references': [{'pmid': '24370846', 'type': 'BACKGROUND', 'citation': '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': '22723585', 'type': 'BACKGROUND', 'citation': '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': '22354959', 'type': 'BACKGROUND', 'citation': "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': '8280078', 'type': 'BACKGROUND', 'citation': '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': '8168691', 'type': 'BACKGROUND', 'citation': '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': '21187061', 'type': 'BACKGROUND', 'citation': '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': '11812757', 'type': 'BACKGROUND', 'citation': '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': '11872657', 'type': 'BACKGROUND', 'citation': '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': '11375325', 'type': 'BACKGROUND', 'citation': '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': '11134101', 'type': 'BACKGROUND', 'citation': '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': '12221216', 'type': 'BACKGROUND', 'citation': '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': '19155592', 'type': 'BACKGROUND', 'citation': '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': '20208358', 'type': 'BACKGROUND', 'citation': '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': '11679451', 'type': 'BACKGROUND', 'citation': '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': '29890724', 'type': 'DERIVED', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': "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.", 'detailedDescription': "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.\n\nSome 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.\n\nClinical 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.\n\nAlthough 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.\n\nOBJECTIVES\n\n* 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.\n* 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.\n* 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."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Healthy participants:\n\n * Adult males and non-pregnant females\n * Normal weight\n * Non-smokers\n * Free of any disease or illness\n * Do not regular take any medications\n * Have a primary care physician\n* Diabetes participants:\n\n * Well-controlled diabetes on diet and/or oral antihyperglycemic agents\n * Not taking insulin\n * Free of any major illness\n * Have a primary care physician\n\nExclusion Criteria:\n\n* Healthy participants:\n\n * Age \\<18 or \\>75y, Pregnant female\n * Regular medication use\n * Complementary or alternative medicine (CAM) use\n * BMI\\<18.5kg/m2, \\>30kg/m2\n * Prediabetes or diabetes (HbA1c≥6%, FBG≥6.1mmol/L)\n * Hypertension (BP≥140/90), Dyslipidemia (Canadian Cardiovascular Society guidelines)\n * Metabolic syndrome (harmonized definition)\n * Polycystic ovarian syndrome\n * Cardiovascular disease\n * Gastrointestinal disease\n * Previous bariatric surgery\n * Liver disease (abnormal liver enzymes)\n * Hyperthyroidism (abnormal TSH)\n * Hypothyroidism (abnormal TSH)\n * Nephropathy (albumin-to-creatinine ratio \\[ACR\\] \\>20)\n * Chronic kidney disease (eGFR \\>60ml/min/1.73m2)\n * Inflammatory conditions (CRP\\>3g/L)\n * Acute or chronic infection (abnormal white blood cell count (WBC), CRP\\>3g/L)\n * Anemia (abnormal Hb)\n * Lung disease\n * Cancer/malignancy\n * Psychiatric illness\n * Major surgery in the last 6 months\n * Other major illness\n * Smoker\n * Heavy alcohol use (\\>3 drinks/day)\n* Diabetes participants:\n\n * Age \\<18 or \\>75y\n * Pregnant female\n * Poorly controlled diabetes (HbA1c\\>7.5%)\n * Recent diabetes medication change (\\< 3 months)\n * Insulin use\n * Complementary or alternative medicine (CAM) use\n * BMI\\<18.5kg/m2, ≥35kg/m2\n * Cardiovascular disease\n * Retinopathy\n * Neuropathy\n * Diabetic foot\n * Gastrointestinal disease\n * Previous bariatric surgery\n * Liver disease (abnormal liver enzymes)\n * Hyperthyroidism (abnormal TSH)\n * Hypothyroidism (abnormal TSH)\n * Anemia (abnormal Hb)\n * Nephropathy (albumin-to-creatinine ratio \\[ACR\\] \\>20)\n * Chronic kidney disease (eGFR \\>60ml/min/1.73m2)\n * Inflammatory conditions (CRP\\>3g/L)\n * Acute or chronic infection (abnormal WBC, CRP\\>3g/L)\n * Lung disease\n * Cancer/malignancy\n * Psychiatric illness\n * Major surgery in the last 6 months\n * Other major illness\n * Smoker\n * Heavy alcohol use (\\>3 drinks/day)'}, 'identificationModule': {'nctId': 'NCT02459834', 'briefTitle': 'The Fructose and Allulose Catalytic Effects (FACE) Trial', 'organization': {'class': 'OTHER', 'fullName': 'University of Toronto'}, 'officialTitle': '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', 'orgStudyIdInfo': {'id': 'UT-FACE 2015'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Allulose + 75g OGTT', 'description': '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.', 'interventionNames': ['Other: Allulose']}, {'type': 'EXPERIMENTAL', 'label': 'Fructose + 75g OGTT', 'description': '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.', 'interventionNames': ['Other: Fructose']}, {'type': 'ACTIVE_COMPARATOR', 'label': '75g OGTT (Control)', 'description': '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.', 'interventionNames': ['Other: Control']}], 'interventions': [{'name': 'Allulose', 'type': 'OTHER', 'otherNames': ['D-psicose'], 'description': '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.', 'armGroupLabels': ['Allulose + 75g OGTT']}, {'name': 'Fructose', 'type': 'OTHER', 'description': '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.', 'armGroupLabels': ['Fructose + 75g OGTT']}, {'name': 'Control', 'type': 'OTHER', 'description': '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.', 'armGroupLabels': ['75g OGTT (Control)']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'M5C 2T2', 'city': 'Toronto', 'state': 'Ontario', 'country': 'Canada', 'facility': "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", 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}], 'overallOfficials': [{'name': 'John L Sievenpiper, MD PhD FRCPC', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Toronto'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Toronto', 'class': 'OTHER'}, 'collaborators': [{'name': 'Tate & Lyle', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Associate Professor', 'investigatorFullName': 'John Sievenpiper', 'investigatorAffiliation': 'University of Toronto'}}}}