AgingPhase 1/2SGLT2iNCT04401904
SGLT2 Inhibition in Older Obese Adults With Pre-diabetes
A Phase 1/2 study testing Dapagliflozin 10 mg and Nutritional counseling in people with Aging, run by The University of Texas Health Science Center at San Antonio at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 60 years and olderHealthy volunteers can take part
- Conditions the study is for
- Aging
- What is being tested?
- Dapagliflozin 10 mg and Nutritional counseling
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesUnited States
- Study dates
- 25 Jun 2020to 14 Sep 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Texas Diabetes Institute - University Health System
San Antonio, Texas, 78207
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
About this study
Official title: Effect of SGLT2 Inhibition on Aging-related Biomarkers in Older Obese Adults With Pre-diabetes
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.
Read the 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.
- Conditions
- Aging
- Being tested
- Dapagliflozin 10 mg, Nutritional counseling
- Keywords
- pre-diabetes, aging, glucose metabolism, borderline diabetes
- Medical subject headings
- Glucose Intolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dapagliflozin 10 mgDrug
Also called Farxiga
10 participants randomized to receive 12 weeks of daily dapagliflozin 10mg by mouth
Nutritional counselingBehavioural
10 participants randomized to receive 12 weeks of weekly counseling on nutrition
| Study group | Role | What they receive |
|---|---|---|
| Dapagliflozin | Experimental | 10 participants with pre-diabetes will be randomized to the experimental group to receive dapagliflozin 10mg by mouth daily for 12 weeks. Receives: Drug: Dapagliflozin 10 mg |
| Nutritional Counseling | Other | 10 participants with pre-diabetes will be randomized to receive nutritional counseling weekly for 12 weeks Receives: Behavioral: Nutritional counseling |
What is being measured
The primary outcome is the main question the study is designed to answer.
AGE-RAGE Measurement in Plasma
Change in AGE-RAGE measured by enzyme-linked immunosorbent assay (ELISA).
Measured: Baseline to 12 weeks
Secondary outcomes (2)
Grip Strength
Change in grip strength measured using a hand-held dynamometer in Newton meters (Nm)
Measured: Baseline to 12 weeks
6 Minute Walking Distance
Change in walking distance in the 6 minute walking test.
Measured: Baseline to 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2020
- Study start25 Jun 2020
- Primary completion14 Sep 2022
- Study completion14 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AgingStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center at San AntonioThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Carolina Solis-Herrera, Principal investigator, University of Texas Health at San Antonio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04401904
- Sponsor's protocol ID
- HSC20190766H
- Other IDs
- 2P30AG044271
- Acronym
- SGLT2i
- Status last verified
- Jan 2024
- First submitted
- 22 Apr 2020
- Last updated
- 5 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Protocol, Statistical Analysis Plan, Published data
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of SGLT2 Inhibition on Aging-related Biomarkers in Older Obese Adults With Pre-diabetes
- ClinicalTrials.gov ID
- NCT04401904
- Acronym / sponsor ID
- SGLT2i / HSC20190766H
- Conditions
- Aging
- Keywords
- pre-diabetes, aging, glucose metabolism, borderline diabetes
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center at San AntonioUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 25 Jun 2020 (actual)
- Primary completion
- 14 Sep 2022 (actual)
- Study completion
- 14 Sep 2022 (actual)
- First posted
- 26 May 2020 (actual)
- Results
- Posted 5 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Dapagliflozin | Experimental | Drug: Dapagliflozin 10 mg10 participants with pre-diabetes will be randomized to the experimental group to receive dapagliflozin 10mg by mouth daily for 12 weeks. |
| Nutritional Counseling | Other | Behavioral: Nutritional counseling10 participants with pre-diabetes will be randomized to receive nutritional counseling weekly for 12 weeks |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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).
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dapagliflozin 10 mgAlso: Farxiga10 participants randomized to receive 12 weeks of daily dapagliflozin 10mg by mouth | Drug | Dapagliflozin |
| Nutritional counseling10 participants randomized to receive 12 weeks of weekly counseling on nutrition | Behavioural | Nutritional Counseling |
Primary outcome
AGE-RAGE Measurement in Plasma
Time frame: Baseline to 12 weeks
Change in AGE-RAGE measured by enzyme-linked immunosorbent assay (ELISA).
2 secondary outcomes
Grip Strength
Time frame: Baseline to 12 weeks
6 Minute Walking Distance
Time frame: Baseline to 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Protocol, Statistical Analysis Plan, Published data
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carolina Solis-Herrera principal investigator
University of Texas Health at San Antonio
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Dapagliflozin 10 mg and Nutritional counseling in people with Aging, run by The University of Texas Health Science Center at San Antonio at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AGE-RAGE Measurement in Plasma (time frame: Baseline to 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2024.