Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

SGLT2 Inhibition in Older Obese Adults With Pre-diabetes (SGLT2i)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04401904
Recruitment Status : Not yet recruiting
First Posted : May 26, 2020
Last Update Posted : May 26, 2020
Sponsor:
Information provided by (Responsible Party):
The University of Texas Health Science Center at San Antonio

Brief Summary:
Inhibitors of the sodium-glucose co-transporter (SGLT2) are FDA-approved for the treatment of type 2 diabetes (T2DM). Their mechanism of action involves lowering of blood glucose concentration secondary to increased glucose excretion of glucose by the kidney. These drugs also improve body weight, blood pressure, and cardiac function. Based on these pleiotropic effects, including its calorie restriction-mimetic properties, the study team hypothesize that SGLT2 drugs will impact several basic aging-related processes, including reductions in oxidative damage to DNA and proteins, advanced glycation end products (AGE) and receptor for AGE (RAGE), cellular senescence, and mitochondrial function.

Condition or disease Intervention/treatment Phase
Aging Drug: Dapagliflozin 10 mg Behavioral: Nutritional counseling Phase 1 Phase 2

Detailed Description:

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prediabetes

Arm Intervention/treatment
Experimental: Dapagliflozin
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

Nutritional Counseling
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




Primary Outcome Measures :
  1. AGE-RAGE measurement in urine [ Time Frame: Baseline to 12 weeks ]
    Change in AGE-RAGE measured by enzyme-linked immunosorbent assay (ELISA).


Secondary Outcome Measures :
  1. 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.

  2. Insulin Sensitivity [ Time Frame: Baseline to 12 weeks ]
    Percentage of change in insulin sensitivity using the Matsuda index derived from the Oral GlucoseTolerance test.

  3. Oxidative Stress [ Time Frame: Baseline to 12 weeks ]
    Change in reactive oxygen species (ROS) production using the Oxygraph instrument.

  4. 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)).

  5. DNA methylation [ Time Frame: Baseline to 12 weeks ]
    Change in DNA methylation and epigenetic clock.

  6. Grip Strength [ Time Frame: Baseline to 12 weeks ]
    Change in grip strength measured using a hand-held dynamometer in Newton meters (Nm)

  7. Isometric knee extension [ Time Frame: Baseline to 12 weeks ]
    Change in isometric torque using a Biodex dynamometer (Nm)

  8. 6 minute walking distance [ Time Frame: Baseline to 12 weeks ]
    Change in walking distance in the 6 minute walking test.

  9. Volumes of maximal oxygen uptake (VO2 max) [ Time Frame: Baseline to 12 weeks ]
    Change % in VO2 max measured by cardiopulmonary exercise testing (CPET)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Men or post-menopausal women.
  2. Age= 60+ years.
  3. All ethnic groups.
  4. Body Mass index (BMI) between 30-37 kg/m2.
  5. Diagnosis of pre-diabetes (HbA1c 5.7-6.4% and 2 hr. Oral Glucose Tolerance Test (OGTT) glucose between 140-199 mg/dL, evaluated at Visit 1 and 2).
  6. Stable body weight (±3% for ≥3 months).
  7. Willing to adhere to medication regimen for three months.
  8. Montreal Cognitive Assessment score ≥21

Exclusion Criteria:

  1. Diagnosis of diabetes based on American Diabetes Association (ADA) criteria
  2. Impaired renal function with estimated Glomerular Filtration Rate (eGFR) < 45 mL/min/1.73m2 .
  3. Impaired liver function with labs ≥3 times upper limits of normal range
  4. Abnormal hematocrit with lower limits of ≤30%
  5. Abnormal triglycerides with upper limits ≥600 mg/dL
  6. Abnormal Thyroid stimulating hormone (TSH) values ≤0.3 and ≥10
  7. Urinalysis results with ˃ 5-10 white blood cell count
  8. Concomitant medications known to affect glucose and lipid homeostasis (anti-diabetes medications, glucocorticoids, atypical antipsychotics, anti-transplant rejection medications, anti-retrovirals).
  9. Current treatment with anticoagulants (warfarin). Aspirin (up to 325 mg) and clopidogrel will be permitted if these can be held for seven days prior to the biopsies.
  10. History of recent cardiovascular event in the last 6 months or Heart Failure (New York Heart Classification greater than class III-IV; recent EKG changes that suggest active heart disease
  11. Poorly controlled blood pressure (systolic BP>180, diastolic BP>100 mmHg).
  12. Active inflammatory, autoimmune, infectious, hepatic, gastrointestinal, malignant, and uncontrolled psychiatric disease (Subjects with depression, anxiety, PTSD, etc. can enroll if controlled and on stable medication)

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Carolina Solis-Herrera, MD 210-567-6691 solisherrera@uthscsa.edu
Contact: Antoinette Lewis 210-450-8023 lewisa@uthscsa.edu

Locations
Layout table for location information
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
Sponsors and Collaborators
The University of Texas Health Science Center at San Antonio
Investigators
Layout table for investigator information
Principal Investigator: Carolina Solis-Herrera University of Texas Health at San Antonio
Layout table for additonal information
Responsible Party: The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier: NCT04401904    
Other Study ID Numbers: HSC20190766H
First Posted: May 26, 2020    Key Record Dates
Last Update Posted: May 26, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Protocol, Statistical Analysis Plan, Published data
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: After study completion, upon publication of data and on ClinicalTrials.gov 1 year after primary completion date of study.
Access Criteria: Data will be analysed by a statistician for publication and by direct communication with the principal investigator

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by The University of Texas Health Science Center at San Antonio:
pre-diabetes
aging
glucose metabolism
borderline diabetes
Additional relevant MeSH terms:
Layout table for MeSH terms
Prediabetic State
Glucose Intolerance
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hyperglycemia
2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs