SGLT2 Inhibition in Older Obese Adults With Pre-diabetes

NCT04401904 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: HSC20190766H2P30AG044271
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

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.

Conditions

Aging

Keywords

pre-diabetes; aging; glucose metabolism; borderline diabetes

Outcome Measures

Primary Outcomes (1)

• AGE-RAGE Measurement in Plasma

  Change in AGE-RAGE measured by enzyme-linked immunosorbent assay (ELISA).

  Baseline to 12 weeks

Secondary Outcomes (2)

• Grip Strength

  Baseline to 12 weeks

• 6 Minute Walking Distance

  Baseline to 12 weeks

Study Arms (2)

Dapagliflozin

EXPERIMENTAL

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

Nutritional Counseling

OTHER

10 participants with pre-diabetes will be randomized to receive nutritional counseling weekly for 12 weeks

Behavioral: Nutritional counseling

Interventions

Dapagliflozin 10 mg DRUG

10 participants randomized to receive 12 weeks of daily dapagliflozin 10mg by mouth

Also known as: Farxiga

Dapagliflozin

Nutritional counseling BEHAVIORAL

10 participants randomized to receive 12 weeks of weekly counseling on nutrition

Nutritional Counseling

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or post-menopausal women.
• Age= 60+ years.
• All ethnic groups.
• Body Mass index (BMI) between 30-38 kg/m2.
• 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).
• Stable body weight (±3% for ≥3 months).
• Willing to adhere to medication regimen for three months.
• Montreal Cognitive Assessment score ≥21

You may not qualify if:

• Diagnosis of diabetes based on American Diabetes Association (ADA) criteria
• Impaired renal function with estimated Glomerular Filtration Rate (eGFR) \< 45 mL/min/1.73m2 .
• Impaired liver function with labs ≥3 times upper limits of normal range
• Abnormal hematocrit with lower limits of ≤30%
• Abnormal triglycerides with upper limits ≥600 mg/dL
• Abnormal Thyroid stimulating hormone (TSH) values ≤0.3 and ≥10
• Urinalysis results with ˃ 5-10 white blood cell count
• Concomitant medications known to affect glucose and lipid homeostasis (anti-diabetes medications, glucocorticoids, atypical antipsychotics, anti-transplant rejection medications, anti-retrovirals).
• 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.
• 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
• Poorly controlled blood pressure (systolic BP\>180, diastolic BP\>100 mmHg).
• 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)
• Blood donation within 2 months prior to enrollment
• History of frequent UTI

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• National Institute on Aging (NIA): collaborator

Study Sites (2)

Texas Diabetes Institute - University Health System

San Antonio, Texas, 78207, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Glucose Intolerance

Interventions

dapagliflozin; Nutrition Assessment

Condition Hierarchy (Ancestors)

Hyperglycemia; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Epidemiologic Measurements; Public Health; Environment and Public Health

Results Point of Contact

• Title: Carolina Solis-Herrera, MD
• Organization: UT Health San Antonio

solisherrera@uthscsa.edu

210-567-4900

Study Officials

• Carolina Solis-Herrera

  University of Texas Health at San Antonio

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 22, 2020
• First Posted: May 26, 2020
• Study Start: June 25, 2020
• Primary Completion: September 14, 2022
• Study Completion: September 14, 2022
• Last Updated: January 5, 2024
• Results First Posted: January 5, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, 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

Locations

US (2)