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Randomized Controlled Trial
. 2023 Feb 28;15(5):1238.
doi: 10.3390/nu15051238.

Rationale, Design and Participants Baseline Characteristics of a Crossover Randomized Controlled Trial of the Effect of Replacing SSBs with NSBs versus Water on Glucose Tolerance, Gut Microbiome and Cardiometabolic Risk in Overweight or Obese Adult SSB Consumer: Strategies to Oppose SUGARS with Non-Nutritive Sweeteners or Water (STOP Sugars NOW) Trial and Ectopic Fat Sub-Study

Sabrina Ayoub-Charette  1   2 , Néma D McGlynn  1   2 , Danielle Lee  1   2 , Tauseef Ahmad Khan  1   2 , Sonia Blanco Mejia  1   2 , Laura Chiavaroli  1   2 , Meaghan E Kavanagh  1   2 , Maxine Seider  3 , Amel Taibi  1 , Chuck T Chen  1 , Amna Ahmed  1   2 , Rachel Asbury  4   5 , Madeline Erlich  1   2   5 , Yue-Tong Chen  1 , Vasanti S Malik  1   6 , Richard P Bazinet  1 , D Dan Ramdath  7   8 , Caomhan Logue  9 , Anthony J Hanley  1   10   11 , Cyril W C Kendall  1   2   8 , Lawrence A Leiter  1   2   12   13   14 , Elena M Comelli  1 , John L Sievenpiper  1   2   12   13   14
Affiliations
Randomized Controlled Trial

Rationale, Design and Participants Baseline Characteristics of a Crossover Randomized Controlled Trial of the Effect of Replacing SSBs with NSBs versus Water on Glucose Tolerance, Gut Microbiome and Cardiometabolic Risk in Overweight or Obese Adult SSB Consumer: Strategies to Oppose SUGARS with Non-Nutritive Sweeteners or Water (STOP Sugars NOW) Trial and Ectopic Fat Sub-Study

Sabrina Ayoub-Charette et al. Nutrients. .

Abstract

Background: Health authorities are near universal in their recommendation to replace sugar-sweetened beverages (SSBs) with water. Non-nutritive sweetened beverages (NSBs) are not as widely recommended as a replacement strategy due to a lack of established benefits and concerns they may induce glucose intolerance through changes in the gut microbiome. The STOP Sugars NOW trial aims to assess the effect of the substitution of NSBs (the "intended substitution") versus water (the "standard of care substitution") for SSBs on glucose tolerance and microbiota diversity.

Design and methods: The STOP Sugars NOW trial (NCT03543644) is a pragmatic, "head-to-head", open-label, crossover, randomized controlled trial conducted in an outpatient setting. Participants were overweight or obese adults with a high waist circumference who regularly consumed ≥1 SSBs daily. Each participant completed three 4-week treatment phases (usual SSBs, matched NSBs, or water) in random order, which were separated by ≥4-week washout. Blocked randomization was performed centrally by computer with allocation concealment. Outcome assessment was blinded; however, blinding of participants and trial personnel was not possible. The two primary outcomes are oral glucose tolerance (incremental area under the curve) and gut microbiota beta-diversity (weighted UniFrac distance). Secondary outcomes include related markers of adiposity and glucose and insulin regulation. Adherence was assessed by objective biomarkers of added sugars and non-nutritive sweeteners and self-report intake. A subset of participants was included in an Ectopic Fat sub-study in which the primary outcome is intrahepatocellular lipid (IHCL) by 1H-MRS. Analyses will be according to the intention to treat principle.

Baseline results: Recruitment began on 1 June 2018, and the last participant completed the trial on 15 October 2020. We screened 1086 participants, of whom 80 were enrolled and randomized in the main trial and 32 of these were enrolled and randomized in the Ectopic Fat sub-study. The participants were predominantly middle-aged (mean age 41.8 ± SD 13.0 y) and had obesity (BMI of 33.7 ± 6.8 kg/m2) with a near equal ratio of female: male (51%:49%). The average baseline SSB intake was 1.9 servings/day. SSBs were replaced with matched NSB brands, sweetened with either a blend of aspartame and acesulfame-potassium (95%) or sucralose (5%).

Conclusions: Baseline characteristics for both the main and Ectopic Fat sub-study meet our inclusion criteria and represent a group with overweight or obesity, with characteristics putting them at risk for type 2 diabetes. Findings will be published in peer-reviewed open-access medical journals and provide high-level evidence to inform clinical practice guidelines and public health policy for the use NSBs in sugars reduction strategies.

Trial registration: ClinicalTrials.gov identifier, NCT03543644.

Keywords: glucose control; glycemia; gut microbiota; low- and no-calorie sweeteners; overweight; randomized controlled trial; sugar-sweetened beverages; sweetening agents; type 2 diabetes; water.

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Conflict of interest statement

S.A.-C. avoids consuming NSBs and SSBs and has received an honorarium from the international food information council (IFIC) for a talk on artificial sweeteners, the gut microbiome, and the risk for diabetes. N.D.M. was a former employee of Loblaw Companies Limited and current employee of Enhanced Medical Nutrition. She has completed consulting work for contract research organizations, restaurants, start-ups, the International Food Information Council, and the American Beverage Association, all of which occurred outside of the submitted work. T.A.K. has taken honorarium for lectures from International Food Information Council (IFIC) and Institute for the Advancement of Food and Nutrition Sciences (IAFNS; formerly ILSI North America). LC was previously employed as a casual clinical coordinator at INQUIS Clinical Research, Ltd. (formerly Glycemic Index Laboratories, Inc.), a contract research organization. M.E.K. has received funding from a Toronto 3D PhD Scholarship award and the CIHR Canadian Graduate Scholarship Doctoral Award and is a part-time employee at INQUIS Clinical Research, Ltd., a contract research organization. R.A. has received funding from the CIHR Canada Graduate Scholarships Master’s Award and the Ontario Graduate Scholarship (OGS). M.E. has received funding from the United Soybean Board (the United States Department of Agriculture [USDA] Soy “Check-off” Program) and a CIHR Canadian Graduate Scholarships Master’s Award. V.S.M. has received funding from the Government of Canada through the Canada Research Chair Endowment, Connaught New Researcher Award, The Joannah & Brian Lawson Centre for Child Nutrition, University of Toronto; Temerty Faculty of Medicine Pathway Grant, University of Toronto; Canada Foundation for Innovation; Ontario Research Fund. She has served as a consultant for the City and County of San Francisco for litigation related to health warning labels on soda. R.P.B. has received industrial grants, including those matched by the Government of Canada through the Canada Research Chair Endowment, and/or travel support or consulting fees largely related to work on brain fatty acid metabolism from Arctic Nutrition, Bunge Ltd., DSM, Fonterra Inc, Mead Johnson, Natures Crops International, Nestec Inc. Pharmavite, and Sancero Inc. He is on the executive of the International Society for the Study of Fatty Acids and Lipids and held a meeting on behalf of Fatty Acids and Cell Signaling, both of which rely on corporate sponsorship. Dr. Bazinet has given expert testimony in relation to supplements and the brain. D.D.R. has received research support from Pulse Canada, the Saskatchewan Pulse Growers Association, and the Ontario Bean Growers Association. He has no other conflict of interest to declare. A.J.H. holds investigator-initiated research funds from Dairy Farmers of Canada. C.W.C.K. has received grants or research support from the Advanced Food Materials Network, Agriculture and Agri-Foods Canada, Almond Board of California, American Pistachio Growers, Barilla, Calorie Control Council, Canadian Institutes of Health Research, Canola Council of Canada, International Nut and Dried Fruit Council, International Tree Nut Council Research and Education Foundation, Loblaw Brands, Pulse Canada, Saskatchewan Pulse Growers and Unilever; has received in-kind research support from the Almond Board of California, American Peanut Council, Barilla, California Walnut Commission, Kellogg Canada, Loblaw Companies, Quaker (PepsiCo), Primo, Unico, Unilever, WhiteWave Foods; has received travel support or honorariums from the American Peanut Council, American Pistachio Growers, Barilla, California Walnut Commission, Canola Council of Canada, General Mills, International Nut and Dried Fruit Council, International Pasta Organization, Loblaw Brands Ltd., Nutrition Foundation of Italy, Oldways Preservation Trust, Paramount Farms, Peanut Institute, Pulse Canada, Sabra Dipping, Saskatchewan Pulse Growers, Sun-Maid, Tate & Lyle, Unilever and White Wave Foods; has served on the scientific advisory board for the International Tree Nut Council, International Pasta Organization, Lantmannen, McCormick Science Institute, Oldways Preservation Trust, Paramount Farms and Pulse Canada; is a member of the International Carbohydrate Quality Consortium, executive board member of the Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes; is on the Clinical Practice Guidelines Expert Committee for Nutrition Therapy of the European Association for the Study of Diabetes; and is a director of the Toronto 3D Knowledge Synthesis and Clinical Trials Foundation. E.M.C. has received research support from Ocean Spray Cranberries and Lallemand Health Solutions; and has received consultant fees or speaker and travel support from Danone and Lallemand Health Solutions. She held the Lawson Family Chair in Microbiome Nutrition Research at The University of Toronto. J.L.S. has received research support from the Canadian Foundation for Innovation, Ontario Research Fund, Province of Ontario Ministry of Research and Innovation and Science, Canadian Institutes of health Research (CIHR), Diabetes Canada, American Society for Nutrition (ASN), International Nut and Dried Fruit Council (INC) Foundation, National Honey Board (U.S. Department of Agriculture [USDA] honey “Checkoff” program), Institute for the Advancement of Food and Nutrition Sciences (IAFNS; formerly ILSI North America), Pulse Canada, Quaker Oats Center of Excellence, The United Soybean Board (USDA soy “Checkoff” program), The Tate and Lyle Nutritional Research Fund at the University of Toronto, The Glycemic Control and Cardiovascular Disease in Type 2 Diabetes Fund at the University of Toronto (a fund established by the Alberta Pulse Growers), The Plant Protein Fund at the University of Toronto (a fund which has received contributions from IFF), and The Nutrition Trialists Network Research Fund at the University of Toronto (a fund established by an inaugural donation from the Calorie Control Council). He has received food donations to support randomized controlled trials from the Almond Board of California, California Walnut Commission, Peanut Institute, Barilla, Unilever/Upfield, Unico/Primo, Loblaw Companies, Quaker, Kellogg Canada, Danone, Nutrartis, Soylent, and Dairy Farmers of Canada. He has received travel support, speaker fees and/or honoraria from ASN, Danone, Dairy Farmers of Canada, FoodMinds LLC, Nestlé, Abbott, General Mills, Nutrition Communications, International Food Information Council (IFIC), Calorie Control Council, International Sweeteners Association, International Glutamate Technical Committee, Phynova, and Brightseed. He has or has had ad hoc consulting arrangements with Perkins Coie LLP, Tate & Lyle, and Inquis Clinical Research. He is a former member of the European Fruit Juice Association Scientific Expert Panel and former member of the Soy Nutrition Institute (SNI) Scientific Advisory Committee. He is on the Clinical Practice Guidelines Expert Committees of Diabetes Canada, European Association for the study of Diabetes (EASD), Canadian Cardiovascular Society (CCS), and Obesity Canada/Canadian Association of Bariatric Physicians and Surgeons. He serves or has served as an unpaid member of the Board of Trustees and an unpaid scientific advisor for the Carbohydrates Committee of IAFNS. He is a member of the International Carbohydrate Quality Consortium (ICQC), Executive Board Member of the Diabetes and Nutrition Study Group (DNSG) of the EASD, and Director of the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. His spouse is an employee of AB InBev. D.L., S.B.M., M.S., A.T., C.T.C., A.A., Y.T.C., C.L., and L.A.L. reports no relevant competing interests.

Figures

Figure 1
Figure 1
Flow of Participants through the Trial and the Data Collection Schedule. Questionnaires include Personal Information, Demographic Data and Medical History Questionnaires, Symptoms and Craving/Hunger/Satiety Questionnaires and Case Report Forms. formula image = Randomization event: AHRC-REDCap program; Blocked (Latin squares) randomization; Allocation concealment; 1H-MRS = proton magnetic resonance spectroscopy; formula image = Water; formula image = sugar-sweetened beverage (SSB); formula image = non-nutritive sweetened beverage (NSB); N = number; OGTT = 2-h 75 g oral glucose tolerance test.
Figure 2
Figure 2
Flow of Participants through the Trial and the Data Collection Schedule. Text in blue refers to the Ectopic Fat sub-study. 1H-MRS= proton magnetic resonance spectroscopy; BMI = body mass index; BP = blood pressure; COVID-19 = coronavirus disease 2019; GI = gastrointestinal; H2O = water; HIV = human immunodeficiency virus; HTN = hypertension; ITT = intention-to-treat; N = number; NSB = non-nutritive sweetened beverage; SSB = sugar-sweetened beverage; V = visit; WC = waist circumference.
See this image and copyright information in PMC

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