Study of the Reversibility of Glucose Intolerance Caused by Chronic Aspartame Consumption

NCT02520258 | Completed

• 1 other identifier: THU-0887
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

Experiments have shown that some artificial sweeteners like those in diet soda can cause changes in how the body responds to and uses sugar. These changes increase the chance of obesity, type 2 diabetes, and other metabolic diseases. In this study, the investigators plan to see if the most common artificial sweetener, aspartame (brand name Equal, NutraSweet), causes these changes. The investigators believe that if metabolic changes are observed in a person who consumes aspartame, then removing all aspartame from the diet might lead to a reversal of the changes and a normalization of test results.This would impact sweetener additives in our foods and thus decrease the incidence of obesity, diabetes, and the metabolic syndrome.

Conditions

Glucose Metabolism Disorder

Keywords

artificial sweeteners; obesity; diabetes; metabolic syndrome; aspartame

Outcome Measures

Primary Outcomes (2)

• Interval changes in blood glucose

  Phase II (cohort 1): Interval changes in blood glucose will be quantified from area under the curve calculated from oral glucose tolerance tests (OGTT)

  Interval 1: days 1 to 7; interval 2: days 8 to 28; interval 3: days 29 to 35

• Blood glucose

  Phase I (both cohorts): Blood glucose will be quantified from incremental area under the curve calculated from averaged oral glucose tolerance tests (OGTT)

  Screening Visit 2: conducted between day -42 up to Day 1.

Secondary Outcomes (16)

• Interval changes in Glucagon

  Interval 1: days 1 to 7; interval 2: days 8 to 28; interval 3: days 29 to 35

• Glucagon

  Screening Visit 2: conducted between day -42 up to Day 1.

• Interval changes in Peptide Tyrosine Tyrosine (PYY)

  Interval 1: days 1 to 7; interval 2: days 8 to 28; interval 3: days 29 to 35

• Peptide Tyrosine Tyrosine (PYY)

  Screening Visit 2: conducted between day -42 up to Day 1.

• Interval changes in Leptin

  Interval 1: days 1 to 7; interval 2: days 8 to 28; interval 3: days 29 to 35

Other Outcomes (11)

• Interval changes in glycated hemoglobin (HbA1C) - Phase II (Cohort 1)

  Interval 1: days 1 to 7; interval 2: days 8 to 28; interval 3: days 29 to 35

• Glycated hemoglobin (HbA1C) - Phase I (both cohorts)

  Screening Visit 2: conducted between day -42 up to Day 1.

• Interval changes in body mass index (BMI) - Phase II (Cohort 1)

  Interval 1: days 1 to 7; interval 2: days 8 to 28; interval 3: days 29 to 35

Study Arms (2)

Aspartame Consumers - Cohort 1

EXPERIMENTAL

Experimental Group/Arm Phase I - Questionnaires and fasting oral glucose tolerance test (OGTT). Phase II - (If OGTT results are abnormal, participants will be invited to participate in Phase II) Five (5) week study phase with Prudent Metabolic Diet and Intervention of diet soda containing aspartame only; Week 1: Prudent Metabolic Diet and 36oz diet soda po daily, Week 2-4: Prudent Metabolic Diet and no diet soda, Week 5: Prudent Metabolic Diet and 36 oz diet soda po daily.

Other: Oral glucose tolerance test (OGTT); Other: Diet soda containing aspartame only

Aspartame Naive Participants - Cohort 2

ACTIVE COMPARATOR

Control Group/Arm Phase I - Questionnaires and fasting oral glucose tolerance test (OGTT). Phase II - Not applicable for this cohort.

Other: Oral glucose tolerance test (OGTT)

Interventions

Oral glucose tolerance test (OGTT) OTHER

OGTT will be conducted following a ten (10) hour fast on Screening Visit 2 (Screening Visit 2 may be conducted between Day -42 to Day 1).

Aspartame Consumers - Cohort 1; Aspartame Naive Participants - Cohort 2

Diet soda containing aspartame only OTHER

7 days of 36 oz diet soda po daily (Week 1), followed by 21 days washout (Weeks 2-4), and 7 days rechallenge (Week 5); Prudent metabolic diet; Oral glucose tolerance test (OGTT) on days (+/-2) 3, 7, 10, 14, 21, 28, 31, 35

Aspartame Consumers - Cohort 1

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female aged 18 - 45
• Weight stable for at least 3 months prior to screening (\< 5% weight change)
• BMI of 21 - 29
• Cohort 1 - Aspartame Consumers: Primary dietary sweetener is aspartame; consumes at least 36 ounces of diet soda in which aspartame is a primary ingredient (Diet Coke or Diet Dr Pepper) a day for at least 6 months duration prior to study enrollment (Primary dietary sweetener is aspartame" should be defined as: "840g per week sucrose equivalent from aspartame and less than 280 grams per week sucrose equivalent from all other sweeteners (non-caloric and caloric sweeteners). For reference, one 12oz soda is 40g sucrose equivalent, and one teaspoon (one packet) of artificial sweetener is 4g sucrose equivalent.)"
• Cohort 2 - Aspartame Naïve Participants: Consumes less than or equal to 2 cans of diet soda per week
• Screening Visit #2 OGTT Outcome:
• h plasma glucose \< 110 mg/dl AND
• h plasma glucose \< 140 mg/dl
• Abnormal OGTT during the screening phase of the study (area under curve on the high end of distribution)
• Must be able to comply with a metabolic Prudent diet
• Willing to fast 10 hours before each OGTT and BodPod
• Current level of exercise (aerobic and/or resistance training) must be able to be sustained while an in-patient

You may not qualify if:

• Any evidence of US National Cholesterol Education Program Adult Treatment Panel III
• Clinical Identification of the Metabolic Syndrome (must have 3 or more of the following risk factors):
• Abdominal Obesity, given as a waist circumference:
• Men \>102 cm (\>40 in)
• Women \> 88 cm (\>35 in)
• Triglycerides \>150 mg/dl
• HDL Cholesterol:
• Men \< 40 mg/dl
• Women \<50 mg/dl
• Blood Pressure \>130/ \>85 mm Hg
• Fasting Glucose \> 110 mg/dl
• Average systolic blood pressure (SBP) \> 150 mmHg and / or diastolic blood pressure (DBP) \> 90 mmHG (based on 3 BPs taken at screening visit #1),
• LDL-C \> 240mg/dl
• Triglycerides \> 400 mg/dl
• Evidence of a liver disorder (ALT \> three fold of the ULN)

Sponsors & Collaborators

• Rockefeller University: lead

Study Sites (1)

The Rockefeller University

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Glucose Metabolism Disorders; Obesity; Diabetes Mellitus; Metabolic Syndrome

Interventions

Glucose Tolerance Test

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Endocrine System Diseases; Insulin Resistance; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques

Study Officials

• Thomas Huber, MD PhD

  Rockefeller University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Assistant Professor

Study Record Dates

• First Submitted: July 30, 2015
• First Posted: August 11, 2015
• Study Start: August 1, 2015
• Primary Completion: June 25, 2019
• Study Completion: June 25, 2019
• Last Updated: June 4, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)