Study Of Drinks With Artificial Sweeteners in People With Type 2 Diabetes (SODAS)

• ClinicalTrials.gov Identifier: NCT03944616
• Recruitment Status: Recruiting
• First Posted: May 9, 2019
• Last Update Posted: May 16, 2022
• Sponsor: University of California, Irvine
• Collaborators: University of Minnesota; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): Andrew Odegaard, University of California, Irvine

Study Description

Brief Summary:

Diet beverages sweetened with artificial sweeteners occupy a unique category in the food environment as they are a source of intensely sweet taste with no calories. Diet beverages are the single largest contributor to artificial sweetener intake in the U.S. diet, and people with diabetes are the highest consumers of diet beverages, tending to consume them as a replacement for dietary sources of sugar, especially in place of sugar-sweetened beverages. This behavior has been endorsed by dietetic and scientific organizations, and diet beverages are marketed as being synonymous with better health, suitable for weight loss, and thus advantageous for diabetes control. The underlying public health concern is that there are few data to support or refute the benefit or harm of habitual diet beverage consumption by people with diabetes; therefore randomized trials with relevant outcomes must be conducted because they would address many limitations of previous research and have major implications for dietary recommendations on diet beverage intake and primary and secondary prevention of chronic disease. To begin addressing this important scientific gap the investigators are testing the effect of diet beverage intake on diabetes control parameters in free-living adults with type 2 diabetes in a randomized, two arm parallel trial with a run-in period of 2-weeks and an active intervention period of 24-weeks. This study will recruit 200 patients with type 2 diabetes who are usual consumers of commercial diet beverages and randomize them to receive and consume either: 1) A commercial diet beverage of choice (3 servings or 24 oz. daily); or 2) Unflavored bottled water of choice (sparkling or plain) (3 servings or 24 oz. daily). The primary outcome will be a central measure of clinical diabetes control in glycated hemoglobin (HbA1c). The study will also measure the nature and magnitude of glycemic excursions via continuous glucose monitors, as well as clinical markers of cardiometabolic risk and kidney function. Lastly, investigators will measure plausible mechanisms whereby diet beverage intake may alter risk by assessing the effect of diet beverage intake on the functional composition of the gut microbiome via stool samples and comprehensive metabolomics, satiety hormones, as well as usual dietary intake, and upstream behavioral pathways which may inform dietary intake patterns.

Condition or disease	Intervention/treatment	Phase
Type 2 Diabetes	Behavioral: Diet Beverage; Behavioral: Water	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This study is testing the effect of commercial diet beverage intake on diabetes control parameters in free-living adults with type 2 diabetes in a randomized, two arm parallel trial with a run-in period of 2-weeks and an active intervention period of 24-weeks. We will recruit 200 patients with type 2 diabetes who are usual consumers of commercial diet beverages and randomize them to receive and consume either: 1) A commercial diet beverage of choice (3 servings or 24 oz. daily); or 2) Unflavored bottled water of choice (sparkling or plain) (3 servings or 24 oz. daily).
• Masking: Single (Outcomes Assessor)
• Masking Description: All nursing staff/phlebotomist collecting physical samples, and the lab analyzing the samples will be masked to the trial arm the participant is in. The biostatistician performing the final analyses will also be masked.
• Primary Purpose: Prevention
• Official Title: Effect of Artificially Sweetened Beverages on Diabetes Control in Adults With Type 2 Diabetes
• Actual Study Start Date: June 6, 2019
• Estimated Primary Completion Date: February 28, 2023
• Estimated Study Completion Date: February 28, 2023

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Diet Beverage; Participants will receive and consume three daily servings (24 ounces) of a non-caloric commercial diet beverage of their choice sweetened with FDA approved artificial sweeteners.	Behavioral: Diet Beverage; Participants will receive and consume three daily servings (24 ounces) of a non-caloric commercial diet beverage of their choice sweetened with FDA approved artificial sweeteners.
Experimental: Water; Participants will receive and consume three daily servings (24 ounces) of plain bottled/canned water in place of their usual commercial diet beverage. The water will be unflavored, unsweetened, non-caloric, and may be plain or sparkling. Participants randomized to consume water will be instructed to avoid intake of diet beverages.	Behavioral: Water; Participants will receive and consume three daily servings (24 ounces) of plain bottled/canned water in place of their usual commercial diet beverage. The water will be unflavored, unsweetened, non-caloric, and may be plain or sparkling. Participants randomized to consume water will be instructed to avoid intake of diet beverages.

Outcome Measures

Primary Outcome Measures :

1. HbA1c [ Time Frame: 0, 12, 24 weeks ]
   Glycated hemoglobin

Secondary Outcome Measures :

1. Time In Range [ Time Frame: All 14 day periods: Run-in (2-weeks, usual-baseline), weeks 11 and 12 (14 days), weeks 23 and 24 (14 days) ]
   Time in range is collected by a masked Continuous Glucose Monitor (CGM), which measures individual glucose levels every 15 minutes for two weeks via a sensor placed on the participants upper arm (underside). Time in Range is defined as the % of time each day with a glucose measure between 70-180 mg/dl. The range of CGM data for inclusion in this study will be 5 to 14 days, consistent with manufacturer's recommendations.
2. Glycemic Variability [ Time Frame: All 14 day periods: Run-in (2-weeks, usual-baseline), weeks 11 and 12 (14 days), weeks 23 and 24 (14 days) ]
   Glycemic variability is collected by a masked Continuous Glucose Monitor (CGM), which measures individual glucose levels every 15 minutes for two weeks via a sensor placed on the participants upper arm (underside). Glycemic variability is defined as the CV and SD. The range of CGM data for inclusion in this study will be 5 to 14 days, consistent with manufacturer's recommendations.
3. Other CGM metrics [ Time Frame: All 14 day periods: Run-in (2-weeks, usual-baseline), weeks 11 and 12 (14 days), weeks 23 and 24 (14 days) ]
   Multiple metrics are able to be calculated by CGM. The primary secondary endpoint for CGM will be Time In Range. Reporting of any other CGM metrics will be prefaced with this statement and the residual CGM metrics will be analyzed and interpreted cautiously and conservatively. They include: Mean glucose, glycemic variability, and episodes of hypoglycemia/hyperglycemia.
4. Lipid panel (Total cholesterol, LDL cholesterol, HDL cholesterol, Fasting Triglycerides), all mg/dL [ Time Frame: 0, 12, 24 weeks ]
   A lipid panel is a standard measurement for assessing clinical CVD risk
5. Kidney function [ Time Frame: 0, 6, 12, 18, 24 weeks ]
   Serum creatinine is a standard clinical measurement for kidney function
6. Fasting glucose and Insulin [ Time Frame: 0, 6, 12, 18, 24 weeks ]
   Standard clinical measures
7. Fructosamine/Glycated Albumin [ Time Frame: 0, 6, 12, 18, 24 weeks ]
   Fructosamine and glycated albumin levels represent usual glycemia over the past 2-3 weeks, and are considered valid markers of short term clinical glycemic patterns by the American Diabetes Association
8. Blood pressure [ Time Frame: 0, 6, 12, 18, 24 weeks ]
   Systolic and Diastolic blood pressure, standard clinical measurement
9. Weight (kg) [ Time Frame: 0, 6, 12, 18, 24 weeks ]
   Weight measured on standardized scale in gown
10. Dietary Quality (Healthy Eating Index) [ Time Frame: Run-in period (2 weeks), Active intervention (Up to 24 weeks). ]
    Assessed by multiple unannounced 24-hour dietary recalls that will occur during the run-in to assess usual habits (2 recalls over 2 weeks) and the active intervention (5 recalls over 24 weeks), to measure any changes in diet quality metric. Results will be used to calculate a metric of diet quality in the Healthy Eating Index that is based upon the USDA Dietary Guidelines.
11. DHP-18 [ Time Frame: 0, 6, 12, 18, 24 weeks ]
    A diabetes-specific patient reported outcome measure developed to evaluate the health-related quality of life of people living with type 2 diabetes
12. Food Craving Inventory [ Time Frame: 0, 6, 12, 18, 24 weeks ]
    Measures different domains of general and specific food cravings
13. Sleep Quality and Patterns [ Time Frame: 0, 6, 12, 18, 24 weeks ]
    Pittsburgh Sleep Quality Index
14. Physical activity [ Time Frame: All 14 day periods: Run-in (2-weeks, usual-baseline), weeks 11 and 12 (14 days), weeks 23 and 24 (14 days) ]
    Objectively measured via Activpal
15. Serotonin [ Time Frame: 0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses ]
    Chemical and neurotransmitter measured in blood with myriad roles, including appetite and digestion
16. Leptin [ Time Frame: 0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses ]
    Hormone measured in the blood with satiety related role
17. Thyroid Stimulating Hormone (TSH) [ Time Frame: 0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses ]
    Hormone measured in the blood with energy balance related role
18. Neuropeptide Y [ Time Frame: 0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses ]
    Peptide measured in the blood with satiety related role
19. cholecystokinin (CCK) [ Time Frame: 0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses ]
    Peptide measured in the blood with satiety related role
20. Gut Microbiome [ Time Frame: 0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses ]
    Measured with kit: Self-collection and stabilization of microbial DNA from feces for gut microbiome profiling
21. Comprehensive metabolomics [ Time Frame: 0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses ]
    Serum collection for comprehensive metabolomics analysis for integrative analysis with gut microbiome
22. Dietary Practices [ Time Frame: 0, 6, 12, 18, 24 weeks ]
    Short questionnaire assessing dietary behaviors related to meal frequency, timing, and eating away from home

Eligibility Criteria

• Ages Eligible for Study: 35 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion criteria: We will include men, women and non-binary participants with T2D, age 35 years and older, able to provide informed consent, otherwise healthy, who meet the following criteria:

• Physician diagnosed type 2 diabetes ≥ 6 months prior to screening
• HbA1c 6.5-8.5% at participant screening
• Current treatment with lifestyle changes or stable diabetes-related medication levels for the past 3 months
• Willingness to provide consent to contact treating physician and physician agreement to refrain from changing diabetes-related medications during the trial (change defined as > 2 fold change in dose of any 1 hyperglycemic agent or addition or subtraction of an agent)
• No physician-directed medication change for 3 months if prescribed medication for lipids or blood pressure
• Usual consumers of diet beverages (≥ 3 servings/ week (24 oz.) and the willingness to maintain fidelity of the intervention, and participate in all aspects of the intervention
• Not actively looking to make major lifestyle alterations during the study period with stable weight for 2 months (within 3%).

Exclusion Criteria:

• Type 1 diabetes or suspected type 1 diabetes (lean with polyuria, polydipsia, and weight loss with little response to metformin)
• "Secondary" diabetes due to specific causes (e.g. monogenic syndromes, pancreatic surgery, and pancreatitis)
• Diabetic Ketoacidosis hospitalization within last 6 months
• Severe/major hypoglycemia in the last 3 months-severe/major hypoglycemia is defined as a hypoglycemic event in which patient requires assistance of another person to manage the episode
• Glucocorticoid use (prednisone 2.5 mg/d or more or its equivalent)
• History of intolerance or allergy to diet beverages or AS or phenylketonuria
• Any condition that is known to affect the validity of the glycemic measures (Hba1c)
• Major cardiovascular disease event or surgery within past 6 months
• Gastrointestinal disease
• Renal or liver disease
• Current treatment for cancer
• Those with major surgery planned or history of bariatric surgery
• Antibiotic treatment (> 6 days) within past 6 months
• Currently pregnant (via self-report) or planning to become pregnant during study period; <1 year postpartum and breast feeding
• Current participation in another interventional clinical trial
• Previous randomization in this study,
• Heavy alcohol consumption (on average >2 drinks/day for women and >3 drinks/day for men)
• Habitual consumer of SSB ≥ 1 serving / day (8 oz.)
• Does not drink diet beverages
• BMI < 20.0 kg/m2

Contacts and Locations

Contacts

Contact: Andrew Odegaard, PhD, MPH; (949) 824-0920; aodegaar@uci.edu

Contact: Syma Rashid, MBBS; 949-824-0920; srashid1@uci.edu

Locations

United States, California

University of California, Irvine; Recruiting

Irvine, California, United States, 92697

Contact: Syma Rashid, MBBS 949-824-0920 srashid1@uci.edu

United States, Minnesota

University of Minnesota; Recruiting

Minneapolis, Minnesota, United States, 55454

Contact: Sarah Rydell, MPH 612-625-1017 rydell@umn.edu

Sponsors and Collaborators

University of California, Irvine

University of Minnesota

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

More Information

• Responsible Party: Andrew Odegaard, Associate Professor, University of California, Irvine
• ClinicalTrials.gov Identifier: NCT03944616
• Other Study ID Numbers: R01DK117028 [HS# 2018-4756]; 1R01DK117028-01A1 ( U.S. NIH Grant/Contract )
• First Posted: May 9, 2019
• Last Update Posted: May 16, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: It is not yet known if there will be a plan to make IPD available.

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

Keywords provided by Andrew Odegaard, University of California, Irvine:

Diet beverages; diet; diabetes control; artificial sweeteners; continuous glucose monitor; gut microbiome; metabolomics

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases