Study Of Drinks With Artificial Sweeteners in People With Type 2 Diabetes

Type 2 Diabetes Clinical Trial

— SODAS  

Official title:

Effect of Artificially Sweetened Beverages on Diabetes Control in Adults With Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03944616
• Other study ID #: R01DK117028 [HS# 2018-4756]
• Secondary ID: 1R01DK117028-01A
• Status: Completed
• Phase: N/A
• Start date: June 6, 2019
• Est. completion date: March 21, 2024

Study information

• Verified date: June 2024
• Source: University of California, Irvine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 181
• Est. completion date: March 21, 2024
• Est. primary completion date: March 21, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	University of California, Irvine	Irvine	California
United States	University of Minnesota	Minneapolis	Minnesota

Sponsors (3)

Lead Sponsor	Collaborator
University of California, Irvine	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HbA1c	Glycated hemoglobin	0, 12, 24 weeks
Secondary	Time In Range	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.	All 14 day periods: Run-in (2-weeks, usual-baseline), weeks 11 and 12 (14 days), weeks 23 and 24 (14 days)
Secondary	Glycemic Variability	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.	All 14 day periods: Run-in (2-weeks, usual-baseline), weeks 11 and 12 (14 days), weeks 23 and 24 (14 days)
Secondary	Other CGM metrics	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.	All 14 day periods: Run-in (2-weeks, usual-baseline), weeks 11 and 12 (14 days), weeks 23 and 24 (14 days)
Secondary	Lipid panel (Total cholesterol, LDL cholesterol, HDL cholesterol, Fasting Triglycerides), all mg/dL	A lipid panel is a standard measurement for assessing clinical CVD risk	0, 12, 24 weeks
Secondary	Kidney function	Serum creatinine/cystatin-c are standard clinical measurements for kidney function	0, 6, 12, 18, 24 weeks
Secondary	Fasting glucose and Insulin	Standard clinical measures	0, 6, 12, 18, 24 weeks
Secondary	Fructosamine/Glycated Albumin	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	0, 6, 12, 18, 24 weeks
Secondary	Blood pressure	Systolic and Diastolic blood pressure, standard clinical measurement	0, 6, 12, 18, 24 weeks
Secondary	Weight (kg)	Weight measured on standardized scale in gown	0, 6, 12, 18, 24 weeks
Secondary	Dietary Quality (Healthy Eating Index)	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.	Run-in period (2 weeks), Active intervention (Up to 24 weeks).
Secondary	DHP-18	A diabetes-specific patient reported outcome measure developed to evaluate the health-related quality of life of people living with type 2 diabetes	0, 6, 12, 18, 24 weeks
Secondary	Food Craving Inventory	Measures different domains of general and specific food cravings	0, 6, 12, 18, 24 weeks
Secondary	Sleep Quality and Patterns	Pittsburgh Sleep Quality Index	0, 6, 12, 18, 24 weeks
Secondary	Physical activity	Objectively measured via Activpal	All 14 day periods: Run-in (2-weeks, usual-baseline), weeks 11 and 12 (14 days), weeks 23 and 24 (14 days)
Secondary	Serotonin	Chemical and neurotransmitter measured in blood with myriad roles, including appetite and digestion	0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses
Secondary	Leptin	Hormone measured in the blood with satiety related role	0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses
Secondary	Thyroid Stimulating Hormone (TSH)	Hormone measured in the blood with energy balance related role	0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses
Secondary	Neuropeptide Y	Peptide measured in the blood with satiety related role	0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses
Secondary	cholecystokinin (CCK)	Peptide measured in the blood with satiety related role	0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses
Secondary	Gut Microbiome	Measured with kit: Self-collection and stabilization of microbial DNA from feces for gut microbiome profiling	0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses
Secondary	Comprehensive metabolomics	Serum collection for comprehensive metabolomics analysis for integrative analysis with gut microbiome	0, 12, 24 weeks: Samples collected and stabilized at these time points and frozen for future analyses
Secondary	Dietary Practices	Short questionnaire assessing dietary behaviors related to meal frequency, timing, and eating away from home	0, 6, 12, 18, 24 weeks
Secondary	Apolipoprotein-B	ApoB levels indicate the atherogenic particle concentration independent of the particle cholesterol content	0, 12, 24 weeks
Secondary	Apolipoprotein AI (Apo-AI)	Apo-AI the major protein component of high density lipoprotein (HDL)	0, 12, 24 weeks
Secondary	Fibrinogen	A protein involved in forming blood clots in the body	0, 12, 24 weeks
Secondary	C-reactive protein	biomarker of inflammation	0, 12, 24 weeks
Secondary	Liver function panel	Tests that measure various functions of liver	0, 12, 24 weeks
Secondary	Medication Effect Score (MES)	The medication effect score (MES) is a measure of overall diabetes regimen intensity, and is based on the dosages of medications used and their potencies. The MES is calculated for each diabetes medication in a regimen using the following equation: (actual drug dose/maximum drug dose) × drug-specific adjustment factor. The adjustment factor equates to the expected decrease in HbA1c achieved by the drug as monotherapy. The MES presumes a linear relationship between medication dosage and HbA1c, and the sum of MES values attributed to individual medications represents the maximum A1c reduction that may be expected by the regimen. It is a continuous variable with range 0 (no medications), and the maximum achievable MES is patient specific and dependent on the total number of and dose of medications reported.	0, 6, 12, 18, 24 weeks
Secondary	Therapeutic Intensity Score (TIS)	The therapeutic intensity score (TIS) is a summary measure that accounts for the number of medications and the relative doses a patient received to lower blood pressure. It is a continuous variable with range 0 (no medications), and the maximum achievable TIS is patient specific and dependent on the total number of antihypertensive medications reported.	0, 6, 12, 18, 24 weeks
Secondary	Lipid intensity therapy score	Reflects guidelines on intensity of lipid therapy for CVD risk none, low, moderate, high intensity categories	0, 6, 12, 18, 24 weeks