search
Back to results

Non-Nutritive Sweetener Consumption and Glucose Homeostasis in Older Adults With Prediabetes

Primary Purpose

Continuous Glucose Monitoring, Oral Glucose Tolerance, Insulin Sensitivity

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Non-Nutritive Sweetener Intake and impact on glucose homeostasis
Sponsored by
Virginia Polytechnic Institute and State University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Continuous Glucose Monitoring

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age 50+ years
  • Prediabetic (fasting glucose concentration of 100-125 mg/dL, 2-hour oral glucose tolerance test glucose concentration of 140-199 mg/dL, or a HbA1c value of 5.7% to 6.4%)
  • Weight stable for previous 6 months (±2 kg)
  • BMI <40 kg/m2
  • Sedentary to recreationally active
  • No plans to gain/lose weight or change physical activity level
  • Willing to pick up food daily and consume foods provided for an 8-week period
  • Verbal and written informed consent
  • Approval by Medical Director
  • Consume less than one serving of non-nutritive sweetener per week

Exclusion Criteria:

  • BMI >40 kg/m2
  • Diabetes or diabetes medication
  • Antibiotic, prebiotic or prebiotic use in prior 3 months
  • Uncontrolled hypertension (blood pressure (BP) > 159/99 mmHg)
  • Diagnosed inflammatory bowel disease
  • Past or current heart diseases, stroke, respiratory disease, endocrine or metabolic disease, or hematological-oncological disease
  • Vegetarian or vegan
  • Pregnant or plans to become pregnant
  • Breastfeeding
  • Food allergies or aversions, Phenylketonuria (PKU)
  • Estrogen or testosterone usage

Sites / Locations

  • Virginia TechRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Sham Comparator

Arm Label

Aspartame

Sucralose

No NNS

Arm Description

Controlled feeding study. Dosage of aspartame will follow 50% of the acceptable daily intake (equivalent to 25 mg/kg for aspartame). This amount represents 1,500 mg/day of aspartame for a 60 kg adult.

Controlled feeding study. Dosage of sucralose will follow 50% of the acceptable daily intake (equivalent to 2.5 mg/kg for sucralose). This amount represents 150 mg/day of sucralose for a 60 kg adult.

Controlled feeding study with no non-nutritive sweeteners.

Outcomes

Primary Outcome Measures

24-hour glycemic control
The area under the curve (AUC) glucose concentrations, mg/dl from the continuous glucose monitoring at baseline and follow-up will be used

Secondary Outcome Measures

Oral glucose tolerance
Oral glucose tolerance in response to 75 g glucose load; levels of glucose mg/dl will be determined 2 hrs after consuming a 75 glucose load
Insulin Sensitivity
Insulin uU/mL concentrations from the oral glucose tolerance test at baseline and follow-up will be used
Serum Endotoxin
Serum endotoxin mg/L concentrations will be measured at baseline and follow-up
C-reactive protein
C-reactive protein mg/dL concentrations will be measured at baseline and follow-up
Tumor Necrosis Factor alpha
Inflammatory cytokine: Tumor Necrosis Factor alpha pg/mL concentrations will be measured at baseline and follow-up
Interleukin 6
Inflammatory cytokine: Interleukin 6 pg/mL concentrations will be measured at baseline and follow-up
Monocyte chemoattractant protein-1
Inflammatory cytokine: Monocyte chemoattractant protein-1 pg/mL concentrations will be measured at baseline and follow-up

Full Information

First Posted
March 4, 2022
Last Updated
March 16, 2023
Sponsor
Virginia Polytechnic Institute and State University
search

1. Study Identification

Unique Protocol Identification Number
NCT05337098
Brief Title
Non-Nutritive Sweetener Consumption and Glucose Homeostasis in Older Adults With Prediabetes
Official Title
Non-Nutritive Sweetener Consumption (Aspartame and Sucralose) and Glucose Homeostasis in Older Adults With Prediabetes
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 16, 2023 (Actual)
Primary Completion Date
February 29, 2024 (Anticipated)
Study Completion Date
February 29, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Virginia Polytechnic Institute and State University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Animal and observational research in humans suggest that specific types of non-nutritive sweeteners (NNS) may impair glycemic control. However, whether NNS consumption impacts glucose homeostasis in middle-aged/older adults with prediabetes is unknown, and potential mechanisms by which this could occur have yet to be identified. The overall objective of this R21 proposal is to establish proof-of-concept for alterations in glucose homeostasis following intake of sucralose, but not aspartame, in middle-aged/older adults with prediabetes compared to a eucaloric diet with no NNS.
Detailed Description
Observational research has linked intake of non-nutritive sweeteners (NNS), which are consumed daily by ~50% of middle-aged/older U.S. adults, with increased risk of type 2 diabetes (T2D). This risk may be exacerbated by advancing age, which is associated with low-grade chronic inflammation and increased risk of T2D. Current T2D prevention recommendations related to NNS usage are unclear and confusing; use as an alternative to added sugar intake is suggested but long-term NNS use is discouraged despite minimal research to support this recommendation. Animal and observational human studies suggest detrimental effects of some NNS on glucose homeostasis. Longer-term human studies largely demonstrate null findings. Differences in study design and a lack of rigor in existing research contribute to inconclusive findings. In addition, NNS are often studied as a single entity yet types of NNS vary in their absorption and metabolism (e.g., the two most commonly consumed NNS, sucralose and aspartame). Whether NNS consumption impacts glucose homeostasis in middle-aged/older adults with prediabetes is unknown, and potential mechanisms by which this could occur have yet to be identified. The overall objective of this R21 proposal is to establish proof-of-concept for alterations in glucose homeostasis following intake of sucralose, but not aspartame, in middle-aged/older adults with prediabetes compared to a eucaloric diet with no NNS. We will investigate changes in inflammatory markers as potential mechanisms by which sucralose intake influences glucose homeostasis. Following a 2-week eucaloric lead-in diet, 51 middle-aged/older adults (50+ yrs) with prediabetes will be randomly assigned to 1 of 3 controlled feeding conditions for 6 weeks (17 participants per group): sucralose, aspartame, or a control group (no NNS). Standardized diets will be matched for macronutrients (50% carbohydrate, 35% fat, 15% protein) and other variables to avoid the potential confounds of weight change and dietary factors which may influence study outcomes (e.g., added sugars). All groups will receive identical diets, other than the additional NNS for the two NNS groups. 24-hr glycemic control using continuous glucose monitoring and insulin sensitivity and beta cell function via oral glucose tolerance test (OGTT), serum endotoxin, and inflammatory cytokines, including C-reactive protein, will be measured before and following the 6-week dietary treatment period. This research may have clinical practice and policy implications by informing U.S. dietary guidelines and guidelines for T2D prevention, which devote minimal attention to NNS and provide unclear guidance on NNS use due largely to a lack of rigorously-designed controlled feeding trials.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Continuous Glucose Monitoring, Oral Glucose Tolerance, Insulin Sensitivity, Inflammatory Markers

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
51 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Aspartame
Arm Type
Active Comparator
Arm Description
Controlled feeding study. Dosage of aspartame will follow 50% of the acceptable daily intake (equivalent to 25 mg/kg for aspartame). This amount represents 1,500 mg/day of aspartame for a 60 kg adult.
Arm Title
Sucralose
Arm Type
Active Comparator
Arm Description
Controlled feeding study. Dosage of sucralose will follow 50% of the acceptable daily intake (equivalent to 2.5 mg/kg for sucralose). This amount represents 150 mg/day of sucralose for a 60 kg adult.
Arm Title
No NNS
Arm Type
Sham Comparator
Arm Description
Controlled feeding study with no non-nutritive sweeteners.
Intervention Type
Other
Intervention Name(s)
Non-Nutritive Sweetener Intake and impact on glucose homeostasis
Intervention Description
Provision of either aspartame, sucralose, or control with no non-nutritive sweeteners to a controlled feeding study to determine impacts on glucose homeostasis.
Primary Outcome Measure Information:
Title
24-hour glycemic control
Description
The area under the curve (AUC) glucose concentrations, mg/dl from the continuous glucose monitoring at baseline and follow-up will be used
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Oral glucose tolerance
Description
Oral glucose tolerance in response to 75 g glucose load; levels of glucose mg/dl will be determined 2 hrs after consuming a 75 glucose load
Time Frame
6 weeks
Title
Insulin Sensitivity
Description
Insulin uU/mL concentrations from the oral glucose tolerance test at baseline and follow-up will be used
Time Frame
6 weeks
Title
Serum Endotoxin
Description
Serum endotoxin mg/L concentrations will be measured at baseline and follow-up
Time Frame
6 weeks
Title
C-reactive protein
Description
C-reactive protein mg/dL concentrations will be measured at baseline and follow-up
Time Frame
6 weeks
Title
Tumor Necrosis Factor alpha
Description
Inflammatory cytokine: Tumor Necrosis Factor alpha pg/mL concentrations will be measured at baseline and follow-up
Time Frame
6 weeks
Title
Interleukin 6
Description
Inflammatory cytokine: Interleukin 6 pg/mL concentrations will be measured at baseline and follow-up
Time Frame
6 weeks
Title
Monocyte chemoattractant protein-1
Description
Inflammatory cytokine: Monocyte chemoattractant protein-1 pg/mL concentrations will be measured at baseline and follow-up
Time Frame
6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 50+ years Prediabetic (fasting glucose concentration of 100-125 mg/dL, 2-hour oral glucose tolerance test glucose concentration of 140-199 mg/dL, or a HbA1c value of 5.7% to 6.4%) Weight stable for previous 6 months (±2 kg) BMI <40 kg/m2 Sedentary to recreationally active No plans to gain/lose weight or change physical activity level Willing to pick up food daily and consume foods provided for an 8-week period Verbal and written informed consent Approval by Medical Director Consume less than one serving of non-nutritive sweetener per week Exclusion Criteria: BMI >40 kg/m2 Diabetes or diabetes medication Antibiotic, prebiotic or prebiotic use in prior 3 months Uncontrolled hypertension (blood pressure (BP) > 159/99 mmHg) Diagnosed inflammatory bowel disease Past or current heart diseases, stroke, respiratory disease, endocrine or metabolic disease, or hematological-oncological disease Vegetarian or vegan Pregnant or plans to become pregnant Breastfeeding Food allergies or aversions, Phenylketonuria (PKU) Estrogen or testosterone usage
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Valisa Hedrick, PhD
Phone
540-231-7983
Email
vhedrick@vt.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Elaina Marinik, PhD
Phone
540-231-0923
Email
emarinik@vt.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Valisa Hedrick, PhD
Organizational Affiliation
Virginia Polytechnic Institute and State University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Virginia Tech
City
Blacksburg
State/Province
Virginia
ZIP/Postal Code
24061
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Valisa Hedrick, PhD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified study data will be posted to Virginia Tech's data repository, VTechData (https:// data.lib.vt.edu/). Datasets selected for sharing will be made accessible through VTechData, managed by the University Libraries at Virginia Tech. VTechData highlights, preserves, and provides access to data generated at Virginia Tech. The system relies on item/dataset level metadata as the primary building block to data discovery, access, and reuse. Published datasets are to be made accessible for at least five years.
IPD Sharing Time Frame
Data will be available following completion of the trial and will be available for at least 5 years
IPD Sharing Access Criteria
Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA).
IPD Sharing URL
http://data.lib.vt.edu/

Learn more about this trial

Non-Nutritive Sweetener Consumption and Glucose Homeostasis in Older Adults With Prediabetes

We'll reach out to this number within 24 hrs