Effect of NNS on Metformin/GDF15, Pilot

Can Sweetened Drinks Impair Therapeutic Effects of Metformin?

Metformin use for diabetes has the benefit of causing weight loss in some. The investigators in a preclinical trial, demonstrated that mice consuming non-nutritive sweetened (NNS) drinks had worse glucose improvements and weight loss than mice consuming sugar drinks or water. This study will conduct a pilot to determine if this translates into pediatric clinical practice. The hypothesis is that NNS drinks impair metformin-induced satiation, weight loss, and glucose tolerance.

Study Overview

• Status: Recruiting
• Conditions: Obesity, Adolescent; Pre Diabetes
• Intervention / Treatment: Behavioral: avoid sugary and NNS drinks plus start Metformin; Behavioral: avoid sugary drinks (allowed water and drinks sweetened with NNS) plus start Metformin

Detailed Description

This study will enroll 40 children ages 10-21 years (will be recruited from the University of Florida (UF) Pediatric Obesity& Metabolic clinic in Gainesville) and randomize eligible participants into a 2-arm, 12-week Metformin (500mg BID) intervention (n=20/group) in which one arm will be randomized to receive education and counseling to avoid all sweetened drinks (drink water only) and the other to avoid drinks sweetened with sugar (can have diet drinks sweetened with NNS). Participants will be asked to consume minimum of 3 drinks/day In the initial visit (baseline visit) the investigators will do a complete evaluations of physical health and eating behaviors. The investigators will draw lab work including A1c and GDF15 levels. The investigators will also get anthropometric measurements of height and weight to calculate body mass index (BMI). For assessment of beverage intake, the investigators reviewed questionnaires validated in children and adolescents in the past 10 years to better reflect currently available beverages. The investigators combined data from BEVQ-15 (that was validated in children aged 6-18 years) and BFQ(17 items questionnaire validated in young adults, aged 16-30 years),and edited further to make the important distinction between unsweetened and artificially sweetened drinks while adding several examples to each category to help improve correct selection. The investigators will also limit to weekly intake assessments. Data will be collected biweekly. Following completion of the 12-week intervention, participants will return fasting to assess the effectiveness of the metformin treatment on the following: hemoglobin A1C (A1c), Growth Differentiation Factor 15 (GDF15), with BMI and 24-hour dietary recall, including questions about change in hunger while on metformin. The investigators predict that metformin-induced GDF15 levels will be blunted in participants consuming NNS beverages. To improve compliance and decrease attrition, The investigators will provide performance feedback and interpretation of physiological parameters.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Esraa Ismail, MD; Phone Number: 352-294-5069; Email: esraaismail@ufl.edu
• Study Contact Backup: Name: Jennifer Hosford; Phone Number: 352-294-5759; Email: jennifer.hosford@medicine.ufl.edu

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32608
      • Recruiting
      • UF pediatric metabolic and obesity clinic
      • Contact: Angelina Bernier, MD; Phone Number: 352-265-7337

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Eligible patients will have already been prescribed Metformin as part of their normal clinical care
• Must also be aged 10-21 years
• Have a diagnosis of obesity (BMI > 95th%ile or >30 kg/m2 - whichever is lower) and pre-diabetes (A1c between 5.7 and 6.4%)

Exclusion Criteria:

• Previous treatment with oral hypoglycemic medications, (2) resting systolic blood pressure (SBP)>180 mm/Hg or diastolic blood pressure (DBP)>100mm/Hg, (3) self-reported pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Avoid Sugary Drinks and Artificially Sweetened Drinks ( plus Metformin); Counseling on Beverage Intake to avoid sugary sweetened and NNS (non-nutritive sweetened) drinks plus Metformin therapy (subjects will be given 12-week Metformin (500mg BID) as standard of care therapy).	Behavioral: avoid sugary and NNS drinks plus start Metformin; Subjects will receive education and counseling to avoid all sweetened drinks (drink water only). Participants will be asked to consume minimum of 3 drinks/day
Active Comparator: Avoid sugary drinks only, allowed water and drinks with NNS (plus Metformin); Counseling on Beverage Intake to avoid sugary drinks (allowed water and drinks sweetened with NNS) plus Metformin therapy (subjects will be given 12-week Metformin (500mg BID) as standard of care therapy).	Behavioral: avoid sugary drinks (allowed water and drinks sweetened with NNS) plus start Metformin; Subjects will avoid drinks sweetened with sugar (can have diet drinks sweetened with NNS). Participants will be asked to consume minimum of 3 drinks/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in BMI z-score between the two groups at 12 weeks	Compare post-intervention (metformin) body weight between participants randomized to receive education and counseling to either a) avoid all sweetened drinks (drink water only) or b) avoid drinks sweetened with sugar (can have diet drinks sweetened with NNS)	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
improvement of A1C due to metformin between the 2 groups at 12 weeks	Compare post-intervention change in glycemic control between participants randomized to receive education and counseling to either a) avoid all sweetened drinks (drink water only) or b) avoid drinks sweetened with sugar (can have diet drinks sweetened with NNS)	12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
metformin-induced rise in GDF15 in both groups at 12 weeks	Compare post-intervention rise in GDF15 between participants randomized to receive education and counseling to either a) avoid all sweetened drinks (drink water only) or b) avoid drinks sweetened with sugar (can have diet drinks sweetened with NNS)	12 weeks

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Angelina Bernier, MD, University of Florida; Principal Investigator: Esraa Ismail, MD, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2022
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: April 13, 2022
• First Submitted That Met QC Criteria: May 31, 2022
• First Posted (Actual): June 2, 2022

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Pediatric Obesity; Prediabetic State; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: IRB202102435

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No