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Strategies To OPpose Sugars With Non-nutritive Sweeteners Or Water (STOP Sugars NOW) Trial

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ClinicalTrials.gov Identifier: NCT03543644
Recruitment Status : Recruiting
First Posted : June 1, 2018
Last Update Posted : May 20, 2019
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
John Sievenpiper, University of Toronto

Brief Summary:
Health authorities recommend a reduction in added sugars from sugar-sweetened beverages (SSBs) due to risk of obesity and diabetes. As a sugar-reduction strategy, finding the ideal SSB replacement is of the utmost importance. Those who are already consuming SSBs might not easily replace it with water and therefore non-nutritive sweetened beverages (NSBs) present a sweetened alternative, though guidelines recommend water instead of NSBs as a replacement for SSBs. Recent evidence suggests that saccharine, a non-nutritive sweetener, which is not found in NSBs, might induce glucose intolerance by altering gut microbiota in humans. It is currently not known if replacing SSBs with NSBs (which contain low-calorie sweeteners other than saccharine) or water will have any effect on the human gut microbiota and any downstream diabetic risk. The investigators plan to undertake a randomized controlled cross-over trial in 75 healthy adults to assess the effect of replacing SSBs with equal amounts of NSBs or water for 4 weeks on the composition and diversity of human gut microbiota, changes in glucose tolerance and total body fat in those who regularly drink SSBs. Each participant will act as their own control receiving each of the three interventions of SSB, NSB and water for four weeks in random order, each period separated by a four-week wash-out period. All study visits will occur at the Clinical Nutrition and Risk Factor Modification Centre at St. Michael's Hospital. This study will contribute to knowledge that will inform dietary guidelines and public policy with regards to the best possible replacement for SSBs. It will also shed light on the potential mechanism of the adverse effects of NSBs and if the replacement of SSBs by NSBs or water are in fact similar with respect to their effect on gut bacteria and any downstream diabetic risk.

Condition or disease Intervention/treatment Phase
Healthy Overweight and Obesity Metabolic Syndrome PreDiabetes Diabetes Overweight Obesity Dysglycemia Cardiovascular Diseases Cardiovascular Risk Factor Hypertension Other: Sugar-sweetened beverage (SSB) Other: Non-nutritive sweetened beverages (NSB) Other: Water Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Randomized Controlled Trial of the Effect of Replacing Sugar-sweetened Beverages With Non-nutritive Sweetened Beverages or Water on Gut Microbiome and Metabolic Outcomes: STOP Sugars NOW Trial
Actual Study Start Date : May 31, 2018
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : November 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Drinking Water

Arm Intervention/treatment
Active Comparator: Sugar-sweetened beverage (SSB)
The SSB intervention will consist the participants' consuming their usual serving of cans SSBs (each 355 ml, 42 grams sugar) per day. The calories of the SSB group will not be matched to allow for "real-world" substitutions using products available on the market.
Other: Sugar-sweetened beverage (SSB)
SSBs will be provided to each participant. Participants will be able to choose their SSB of choice from the list in the protocol. They will be instructed to drink their usual SSB intake, study drinks provided, while freely consume their usual background diets. They will revert to their usual SSB intake during wash-out phase during which they will not receive any beverage drinks from the study.

Experimental: Non-nutritive sweetened beverage (NSB)
The NSB intervention consists of substituting the participants' usual serving of cans SSBs with NSBs (each 355 ml, 0 grams sugar) per day. The calories of the NSB group will not be matched to allow for "real-world" substitutions using products available on the market.
Other: Non-nutritive sweetened beverages (NSB)
NSBs will be provided to each participant. Participants will be be given the NSB equivalent to the usual SSB chosen from the list in the protocol. They will be instructed to replace their usual SSBs with the NSBs while freely consume their usual background diets. They will revert to their usual SSB intake during wash-out phase during which they will not receive any beverage drinks from the study.

Experimental: Water
The water intervention consists of substituting the participants' usual serving of cans SSBs with bottles or cans of still or sparkling water (each 355 ml bottle or can, 0 grams sugar) per day. The calories of the water group will not be matched to allow for "real-world" substitutions using products available on the market.
Other: Water
Water will be provided to each participant. They will be instructed to replace their usual SSBs with the water while freely consume their usual background diets. They will revert to their usual SSB intake during wash-out phase during which they will not receive any beverage drinks from the study.




Primary Outcome Measures :
  1. Gut microbiome composition measured by 16S rRNA gene sequencing [ Time Frame: Week 0 and week 4 of each intervention ]
  2. 75g OGTT derived plasma glucose iAUC [ Time Frame: Week 0 and week 4 of each intervention ]

Secondary Outcome Measures :
  1. Change in waist circumference [ Time Frame: Week 0 and week 4 of each intervention ]
  2. Change in body weight [ Time Frame: Week 0 and week 4 of each intervention ]
  3. Change in fasting plasma glucose [ Time Frame: Week 0 and week 4 of each intervention ]
  4. 75g OGTT derived 2-hour plasma glucose [2h-PG] [ Time Frame: Week 0 and week 4 of each intervention ]
  5. 75g OGTT derived Matsuda whole body insulin sensitivity index [Matsuda ISI OGTT] [ Time Frame: Week 0 and week 4 of each intervention ]

Other Outcome Measures:
  1. Ectopic fat in liver (intra-hepatocellular lipid [IHCL]) by 1H-MRS (sub-study, n=25) [ Time Frame: Week 0 and week 4 of each intervention ]
  2. Ectopic fat in calf muscles (intra-myocellular lipid [IMCL]) by 1H-MRS (sub-study, n=25) [ Time Frame: Week 0 and week 4 of each intervention ]
  3. Fasting plasma insulin [ Time Frame: Week 0 and week 4 of each intervention ]
  4. 75g OGTT derived iAUC plasma insulin [ Time Frame: Week 0 and week 4 of each intervention ]
  5. 75g OGTT derived maximum concentrations (Cmax) and time to maximum concentrations (Tmax) of plasma glucose [ Time Frame: Week 0 and week 4 of each intervention ]
  6. 75g OGTT derived maximum concentrations (Cmax) and time to maximum concentrations (Tmax) of plasma insulin [ Time Frame: Week 0 and week 4 of each intervention ]
  7. 75g OGTT derived mean incremental plasma glucose [ Time Frame: Week 0 and week 4 of each intervention ]
  8. 75g OGTT derived mean incremental plasma insulin [ Time Frame: Week 0 and week 4 of each intervention ]
  9. Homeostatic model assessment of insulin resistance (HOMA IR) [ Time Frame: Week 0 and week 4 of each intervention ]
  10. Insulin secretion-sensitivity index-2 (ISSI-2) [ Time Frame: Week 0 and week 4 of each intervention ]
  11. Satiety, hunger, and food cravings (using the Control of Eating Questionnaire) [ Time Frame: Week 0 and week 4 of each intervention ]
  12. Diet quality by Alternative Healthy Eating Index (AHEI) (using a weighed three-day diet record) [ Time Frame: Week 0 and week 4 of each intervention ]
  13. Adherence markers - Objective biomarkers of SSBs (increased 13C/12C ratios in serum fatty acids and increased urinary fructose) [ Time Frame: Week 0 and week 4 of each intervention ]
  14. Adherence markers - Objective biomarkers water (decreased 13C/12C ratios in serum fatty acids and decreased urinary fructose) [ Time Frame: Week 0 and week 4 of each intervention ]
  15. Adherence markers - Objective biomarkers NSBs (increased urinary acesulfame potassium and/or sucralose) [ Time Frame: Week 0 and week 4 of each intervention ]
  16. Adherence markers - Beverage logs [ Time Frame: Week 0 and week 4 of each intervention ]
  17. Adherence markers - Returned unused bottles [ Time Frame: Week 0 and week 4 of each intervention ]
  18. Cardiometabolic risk - change in systolic blood pressure [ Time Frame: Week 0 and week 4 of each intervention ]
  19. Cardiometabolic risk - change in diastolic blood pressure [ Time Frame: Week 0 and week 4 of each intervention ]
  20. Cardiometabolic risk - Lipid profile - LDL Cholesterol [ Time Frame: Week 0 and week 4 of each intervention ]
  21. Cardiometabolic risk - Lipid profile - HDL Cholesterol [ Time Frame: Week 0 and week 4 of each intervention ]
  22. Cardiometabolic risk - Lipid profile - non-HDL Cholesterol [ Time Frame: Week 0 and week 4 of each intervention ]
  23. Cardiometabolic risk - Lipid profile - Total Cholesterol [ Time Frame: Week 0 and week 4 of each intervention ]
  24. Cardiometabolic risk - Lipid profile - Triglycerides [ Time Frame: Week 0 and week 4 of each intervention ]
  25. Cardiometabolic risk - C-Reactive Protein (CRP) [ Time Frame: Week 0 and week 4 of each intervention ]
  26. Cardiometabolic risk - urinary sodium [ Time Frame: Week 0 and week 4 of each intervention ]
  27. Cardiometabolic risk - Liver function/injury by ALT [ Time Frame: Week 0 and week 4 of each intervention ]
  28. Cardiometabolic risk - Liver function/injury by AST [ Time Frame: Week 0 and week 4 of each intervention ]
  29. Cardiometabolic risk - Liver function/injury by ALP [ Time Frame: Week 0 and week 4 of each intervention ]
  30. Cardiometabolic risk - Liver function/injury by TBIL [ Time Frame: Week 0 and week 4 of each intervention ]
  31. Cardiometabolic risk - Kidney function/injury by creatinine [ Time Frame: Week 0 and week 4 of each intervention ]
  32. Cardiometabolic risk - Kidney function/injury by eGFR [ Time Frame: Week 0 and week 4 of each intervention ]
  33. Cardiometabolic risk - Kidney function/injury by urinary ACR [ Time Frame: Week 0 and week 4 of each intervention ]
  34. Urinary and blood metabolomic panel [ Time Frame: Week 0 and week 4 of each intervention ]
  35. Urinary and blood proteomic panel [ Time Frame: Week 0 and week 4 of each intervention ]


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, adult (age, 18-75 years) men and non-pregnant women;
  • Overweight or obese (BMI > 23 kg/m2 for Asian individuals and > 25 kg/m2 other individuals);
  • High waist circumference (> 94 cm in men, > 80 cm in women in Europid, Sub-Saharan African, Eastern Mediterranean, and Middle Eastern individuals; > 90 cm in men and > 80 cm in women for South Asian, Chinese, Japanese, and South and Central American individuals
  • Currently report drinking SSBs regularly (≥ 1 serving daily);
  • Have a primary care physician;
  • Nonsmoker;
  • Free of any diseases or illnesses;
  • Not regularly taking any medications that have a clinically relevant effect on the primary outcomes

Exclusion Criteria:

  • Age < 18 or > 75 years;
  • BMI < 23 kg/m2 for Asian individuals and < 25 kg/m2 other individuals;
  • Waist circumference < 94cm in men, < 80cm in women in Europid, Sub-Saharan African, Eastern Mediterranean, and Middle Eastern individuals; < 90cm in men and < 80 cm in women for South Asian, Chinese, Japanese, and South and Central American individuals;
  • Not regularly drinking SSBs (≥1 serving per day);
  • Pregnant or breast feeding females, or women planning on becoming pregnant throughout study duration;
  • Regular medication use (except birth control and PRN meds such as Advil, Tylenol, etc);
  • Antibiotic use in the last 3 months;
  • Complementary or alternative medicine (CAM) use as deemed inappropriate by investigators;
  • Self-reported diabetes;
  • Self-reported hypertension (or systolic blood pressure (BP) ≥ 160 mmHg or diastolic BP ≥ 100 mmHg [26]);
  • Self-reported polycystic ovarian syndrome;
  • Self-reported cardiovascular disease;
  • Self-reported gastrointestinal disease;
  • Previous bariatric surgery;
  • Self-reported liver disease;
  • Self-reported hyperthyroidism or hypothyroidism;
  • Self-reported kidney disease;
  • Self-reported chronic infection;
  • Self-reported lung disease;
  • Self-reported cancer/malignancy;
  • Self-reported schizophrenia spectrum and other psychotic disorders, bipolar and related disorders, and dissociative disorders;
  • Major surgery in the last 6 months;
  • Other major illness or health-related incidence within the last 6 months;
  • Smoker;
  • Regular recreational drug users;
  • Heavy alcohol use (> 3 drinks/day);
  • Do not have a primary care physician;
  • Participation in any trials within the last 6 months or for the duration of this study;
  • Individuals planning on making dietary or physical activity changes throughout study duration;
  • If participating in MRI portion of study: any condition or circumstance which would prevent the participant from having an MRI (e.g. having prostheses or metal implants, tattoos, or claustrophobia)

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): NCT03543644


Contacts
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Contact: Maxine Seider, MSc, RD 416-867-7460 ext 48216 SeiderM@smh.ca
Contact: Tauseef Khan, PhD 416-867-7460 ext 48216 tauseef.khan@utoronto.ca

Locations
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Canada, Ontario
St Michael's Hospital Recruiting
Toronto, Ontario, Canada, M5C2T2
Contact: Maxine Seider, MSc, RD    4168677460 ext 8216    seiderm@smh.ca   
Principal Investigator: John Sievenpiper, MD, PhD, FRCPC         
Sponsors and Collaborators
University of Toronto
Canadian Institutes of Health Research (CIHR)
Investigators
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Principal Investigator: John L Sievenpiper, MD PhD FRCPC University of Toronto
  Study Documents (Full-Text)

Additional Information:
Publications:
World Health Organization, WHO | Sugars intake for adult and children. 2015.
Dietary Guidelines Advisory Committee, 2015-2020 Dietary Guidelines for Americans - health.gov. 2015.
Heart and Stroke Foundation of Canada, Sugar, heart disease and stroke. 2014.
Committee, D.G.A. and Others, Scientific Report of the 2015 Dietary Guidelines Advisory Committee. Washington (DC): USDA and US Department of Health and Human Services, 2015.
Fedorak, R., et al., 546 High Sugar Diets Promote an Inflammatory Microbiota and Reduce Gene Expression Related to Intestinal Barrier Function. Gastroenterology, 2016. 150(4): p. S114-S115.
Canadian Diabetes, A. Waist Circumference. Available from: https://www.diabetes.ca/diabetes-and-you/healthy-living-resources/weight-management/waist-circumference.
Leung AA, Daskalopoulou SS, Dasgupta K, McBrien K, Butalia S, Zarnke KB, Nerenberg K, Harris KC, Nakhla M, Cloutier L, Gelfer M, Lamarre-Cliche M, Milot A, Bolli P, Tremblay G, McLean D, Tran KC, Tobe SW, Ruzicka M, Burns KD, Vallée M, Prasad GVR, Gryn SE, Feldman RD, Selby P, Pipe A, Schiffrin EL, McFarlane PA, Oh P, Hegele RA, Khara M, Wilson TW, Penner SB, Burgess E, Sivapalan P, Herman RJ, Bacon SL, Rabkin SW, Gilbert RE, Campbell TS, Grover S, Honos G, Lindsay P, Hill MD, Coutts SB, Gubitz G, Campbell NRC, Moe GW, Howlett JG, Boulanger JM, Prebtani A, Kline G, Leiter LA, Jones C, Côté AM, Woo V, Kaczorowski J, Trudeau L, Tsuyuki RT, Hiremath S, Drouin D, Lavoie KL, Hamet P, Grégoire JC, Lewanczuk R, Dresser GK, Sharma M, Reid D, Lear SA, Moullec G, Gupta M, Magee LA, Logan AG, Dionne J, Fournier A, Benoit G, Feber J, Poirier L, Padwal RS, Rabi DM; Hypertension Canada. Hypertension Canada's 2017 Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of Hypertension in Adults. Can J Cardiol. 2017 May;33(5):557-576. doi: 10.1016/j.cjca.2017.03.005. Epub 2017 Mar 10. Erratum in: Can J Cardiol. 2017 Dec;33(12 ):1733-1734.
Food and Drug Administration, Multiple Endpoints in Clinical Trials: Guidance for Industry [Draft Guidance]. 2017.
Benjamini, Y. and D. Yekutieli, The control of the false discovery rate in multiple testing under dependency. Annals of statistics, 2001: p. 1165-1188.
Benjamini, Y. and Y. Hochberg, Controlling the false discovery rate: a practical and powerful approach to multiple testing. Journal of the royal statistical society. Series B (Methodological), 1995: p. 289-300.
Noto, H., et al., Long-term Low-carbohydrate Diets and Type 2 Diabetes Risk: A Systematic Review and Meta-analysis of Observational Studies. Journal of General and Family Medicine, 2016. 17(1): p. 60-70.
Health Canada, Draft Guidance Document on Food Health Claims Related to the Reduction in Post-Prandial Glycaemic Response F.D. Bureau of Nutritional Sciences, Health Products and Food Branch Editor. 2013. p. 12.

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Responsible Party: John Sievenpiper, Principal Investigator, Associate Professor, Staff Physician, Scientist, University of Toronto
ClinicalTrials.gov Identifier: NCT03543644     History of Changes
Other Study ID Numbers: CIHR-STOP Sugars NOW
First Posted: June 1, 2018    Key Record Dates
Last Update Posted: May 20, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by John Sievenpiper, University of Toronto:
Microbiome
Sugar Sweetened Beverages
Diet Beverages
Non-Nutritive Sweetened Beverages
Glucose response

Additional relevant MeSH terms:
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Obesity
Metabolic Syndrome
Prediabetic State
Overweight
Cardiovascular Diseases
Overnutrition
Nutrition Disorders
Body Weight
Signs and Symptoms
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Diabetes Mellitus
Endocrine System Diseases