SGLT2 Inhibition in Older Obese Adults With Pre-diabetes (SGLT2i)
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|ClinicalTrials.gov Identifier: NCT04401904|
Recruitment Status : Not yet recruiting
First Posted : May 26, 2020
Last Update Posted : May 26, 2020
|Condition or disease||Intervention/treatment||Phase|
|Aging||Drug: Dapagliflozin 10 mg Behavioral: Nutritional counseling||Phase 1 Phase 2|
Investigations into the aging process have identified major cellular dysfunctions that contribute to aging, including but not limited to increased burden of damaged DNA and protein, reduction in mitochondrial respiration, and the development of pro-inflammatory senescent cells. Developing and testing interventions that interact with multiple points of this spectrum may delay the aging process. Based on prior investigations, the study team believe the SGLT2 inhibitor class of drugs may target these basic mechanisms involved in the aging process and propose testing in a high-risk human population to evaluate their effectiveness in ameliorating aging-associated dysfunctions. Specifically, the investigators hypothesize that SGLT2i drugs will lead to reductions in oxidative damage to DNA and proteins, AGE-RAGE, and cellular senescence, which will be accompanied by improvements in mitochondrial function. If the hypothesis is correct, these findings could lead to the development of new approaches to increase both health-span and lifespan.
This is a single center, open-label, randomized controlled trial. The target enrollment for this pilot study is 20 completed subjects, split evenly between experimental and control groups. Each subject will be randomized to either the experimental group of dapagliflozin 10mg daily for 12 weeks or the control group of nutritional counseling for weight loss. Health-span and clinical evaluations will be taken at baseline and at weeks 10-12 of the study.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||20 completed subjects are planned. Each subject will be randomized to either the experimental group of dapagliflozin 10mg daily for 12 weeks or the control group of nutritional counseling for weight loss.|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Effect of SGLT2 Inhibition on Aging-related Biomarkers in Older Obese Adults With Pre-diabetes|
|Estimated Study Start Date :||August 1, 2020|
|Estimated Primary Completion Date :||August 31, 2021|
|Estimated Study Completion Date :||August 31, 2022|
10 participants with pre-diabetes will be randomized to the experimental group to receive dapagliflozin 10mg by mouth daily for 12 weeks.
Drug: Dapagliflozin 10 mg
10 participants randomized to receive 12 weeks of daily dapagliflozin 10mg by mouth
Other Name: Farxiga
10 participants with pre-diabetes will be randomized to receive nutritional counseling weekly for 12 weeks
Behavioral: Nutritional counseling
10 participants randomized to receive 12 weeks of weekly counseling on nutrition
- AGE-RAGE measurement in urine [ Time Frame: Baseline to 12 weeks ]Change in AGE-RAGE measured by enzyme-linked immunosorbent assay (ELISA).
- Mitochondrial Function [ Time Frame: Baseline to 12 weeks ]Change % on muscle mitochondrial respiration measured in muscle tissue with Oroboros in O2 Flux per mg tissue.
- Insulin Sensitivity [ Time Frame: Baseline to 12 weeks ]Percentage of change in insulin sensitivity using the Matsuda index derived from the Oral GlucoseTolerance test.
- Oxidative Stress [ Time Frame: Baseline to 12 weeks ]Change in reactive oxygen species (ROS) production using the Oxygraph instrument.
- Cellular Senescence [ Time Frame: Baseline to 12 weeks ]Change in senescence cell markers (p16, p21, beta gal) measure by Reverse transcription polymerase chain reaction (RT PCR) (Australia (AU)).
- DNA methylation [ Time Frame: Baseline to 12 weeks ]Change in DNA methylation and epigenetic clock.
- Grip Strength [ Time Frame: Baseline to 12 weeks ]Change in grip strength measured using a hand-held dynamometer in Newton meters (Nm)
- Isometric knee extension [ Time Frame: Baseline to 12 weeks ]Change in isometric torque using a Biodex dynamometer (Nm)
- 6 minute walking distance [ Time Frame: Baseline to 12 weeks ]Change in walking distance in the 6 minute walking test.
- Volumes of maximal oxygen uptake (VO2 max) [ Time Frame: Baseline to 12 weeks ]Change % in VO2 max measured by cardiopulmonary exercise testing (CPET)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04401904
|Contact: Carolina Solis-Herrera, MDfirstname.lastname@example.org|
|Contact: Antoinette Lewisemail@example.com|
|United States, Texas|
|Texas Diabetes Institute - University Health System|
|San Antonio, Texas, United States, 78207|
|University of Texas Health Science Center at San Antonio|
|San Antonio, Texas, United States, 78229|
|Principal Investigator:||Carolina Solis-Herrera||University of Texas Health at San Antonio|