Type2diabetesEarly Phase 1NCT06229678
Ketones, SGLT2, HFrEF
A Early Phase 1 study testing Empagliflozin 25 MG Oral Tablet and Acipimox 250 Mg Oral Capsule in people with Type2diabetes and Heart Failure With Reduced Ejection Fraction, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
Trial summary
The study team will examine the effects of elevated plasma ketone levels following initiation of SGLT2 inhibitor therapy in high-risk type 2 diabetes mellitus (T2DM) individuals with heart failure (HF) with reduced ejection fraction (HFrEF) providing an energy-rich fuel that is taken up with great avidity by the… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Type2diabetes, Heart Failure With Reduced Ejection Fraction
- What is being tested?
- Empagliflozin 25 MG Oral Tablet and Acipimox 250 Mg Oral Capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 71 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Jan 2024to 1 Mar 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 2 Diabetes Mellitus
- Class II-III New York Heart Association (NYHA) heart failure and reduced ejection fraction (EF) <50%
- Age 18-80 years
- BMI 23-44 kg/m2
- Glycated hemoglobin (HbA1c) 6.0-10.0%
- Blood Pressure (BP) ≤ 145/85 mmHg
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- Estimated glomerular filtration rate (eGFR) ≥30 ml/min•1.73 m2
- Only Type 2 diabetics treated with diet/exercise, metformin, sulfonylureas, metformin/sulfonylurea, Glucagon-like peptide-1 receptor agonist (GLP-1 RA), or insulin
- Stable body weight (±4 pounds) over the previous 3 months prior to enrollment
- Ability to understand study procedures and to comply with them for the entire length of the study.
Who cannot join
- Heart failure due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, severe valvular heart disease, hypertrophic obstructive cardiomyopathy.
- Significant change in diuretic management during the month prior to screening (defined by doubling of diuretic dose or addition of another heart failure medication)
- Type 2 Diabetics treated with Dipeptidyl Peptidase-4 Inhibitor (DPP4i) or pioglitazone
- Pregnancy, lactation, or plans to become pregnant. A negative pregnancy test will be performed before each MRI study to assess current status. For women of child-bearing age (WOCBA) willingness to use contraception, if applicable.
- Allergy/sensitivity to study drugs or their ingredients.
- Cancer.
- Current drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- Inability or unwillingness of individual or legal guardian/representative to give written informed consent.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Texas Diabetes Institute - University Health System
San Antonio, Texas, 78207
Sivaram Neppala, MD, 210-358-7200, neppalas@uthscsa.edu
Jemema Rajan, MD, 210-358-7200, rajanj@uthscsa.edu
About this study
Official title: Ketones, Muscle Metabolism, and SGLT2 Inhibitors
The study team will examine the effects of elevated plasma ketone levels following initiation of SGLT2 inhibitor therapy in high-risk type 2 diabetes mellitus (T2DM) individuals with heart failure (HF) with reduced ejection fraction (HFrEF) providing an energy-rich fuel that is taken up with great avidity by the myocardium, to measure change in Left Ventricle diastolic and systolic function
Read the detailed description
The study team will examine the effects of elevated plasma ketones caused by 12-week treatment with an SGLT2i (empagliflozin) treatment in participants with T2DM and HF. The study team will focus on three possible mechanisms of action for these effects and test the following:
(i) Skeletal muscle bioenergetics. Using 31P-MRS, the team will quantify phosphocreatine [PCr], ATP, inorganic phosphate, phosphodiester, and intracellular pH. With 1H-MRS, and will measure intramyocellular lipid content at rest and ATPmax production after exercise. The team will examine the relationships between phosphorous metabolite concentrations, intramyocellular lipid content, and ATP generation before and after 12 weeks of SGLT2 inhibition.
(ii) LV systolic and diastolic function using cardiac MRI in type 2 diabetic patients with Class II-III NYHA heart failure and reduced EF.
(iii) To examine the contribution of the SGLT2i-induced increase in plasma ketone concentration on myocardial function and myocardial blood flow by inhibiting the rise in plasma ketone concentration with acipimox while continuing empagliflozin.
(iv) Improvements in Patient-Reported Outcomes (PRO). Kansas City Cardiomyopathy Questionnaire ( KCCQ) scoring will be used to evaluate self-reported physical function and well-being. This tool is a well-developed and validated method to obtain patient self-reported parameters of health in adults.
- Being tested
- Empagliflozin 25 MG Oral Tablet, Placebo, Acipimox 250 Mg Oral Capsule
- Keywords
- ketones, cardiovascular benefit
- Medical subject headings
- Ketosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Empagliflozin 25 MG Oral TabletDrug
Also called jardiance
Empagliflozin 25MG will be administered orally once per day for 3 months
PlaceboDrug
The placebo will be administered orally once per day for 3 months
Acipimox 250 Mg Oral CapsuleDrug
subjects will be started on acipimox 250mg every 6 hours for 8 days while on continued empagliflozin/placebo therapy. This will be added at the end of 3 months after they finished baseline studies
| Study group | Role | What they receive |
|---|---|---|
| Empagliflozin Group | Experimental | Subjects will be randomized 2:1 to receive empagliflozin, 25mg/day for 3 months Receives: Drug: Empagliflozin 25 MG Oral Tablet; Drug: Acipimox 250 Mg Oral Capsule |
| Placebo group | Placebo comparator | Subjects will be randomized to receive the empagliflozin placebo for 3 months Receives: Drug: Placebo; Drug: Acipimox 250 Mg Oral Capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Phosphocreatine
A measure of phosphocreatine change from baseline to study end
Measured: Baseline to 3 months
Change in Adenosine Triphosphate (ATP)
A measure of ATP change from baseline to study end
Measured: Baseline to 3 months
Change in Inorganic Phosphate
A measure of inorganic phosphate change from baseline to study end
Measured: Baseline to 3 months
Change in Phosphodiester
A measure of phosphodiester change from baseline to study end
Measured: Baseline to 3 months
ATPmax production
Exercise induced ATPmax production change
Measured: Baseline to 3 months
Secondary outcomes (6)
Plasma Beta-hydroxybutyrate (β-OH-B)
Change in β-OH-B with medication
Measured: baseline to 3 months
Acetoacetate concentrations
Change in acetoacetate concentrations
Measured: baseline to 3 months
6-min walking test
Change in the distance that can be covered in a 6 minute walk test
Measured: baseline to 3 months
Patient-Reported Outcomes Measure Information System
By checking KCCQ (Kansas City Cardiomyopathy) scoring: Responses are categorized under 3 sub scales (symptom burden, physical limitation and quality of life) with a range of possible subscale scores from 0 to 100, with 100 representing the least burden of symptoms. The total KCCQ score represents the mean of the three sub scale scores.
Measured: baseline to 3 months
plasma ketone concentration on myocardial function
To examine the contribution of the SGLT2i-induced increase in plasma ketone concentration on myocardial function by inhibiting the rise in plasma ketone concentration with acipimox while continuing empagliflozin.
Measured: Baseline to 3months + 8 days
plasma ketone concentration on myocardial blood flow
To examine the contribution of the SGLT2i-induced increase in plasma ketone concentration on myocardial blood flow by inhibiting the rise in plasma ketone concentration with acipimox while continuing empagliflozin.
Measured: Baseline to 3months + 8 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2024
- Study start25 Jan 2024
- Primary completion1 Nov 2026 (estimated)
- Study completion1 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type2diabetesStudies of the same condition, open and under way.
- 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A randomized (2:1) placebo controlled double blind study
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 71 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Texas Health Science Center at San Antonio
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ralph DeFronzo, MD, Principal investigator, The University of Texas Health Science Center at San Antonio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06229678
- Sponsor's protocol ID
- STUDY00000012
- Other IDs
- R01DK107680
- Status last verified
- Feb 2026
- First submitted
- 18 Dec 2023
- Last updated
- 5 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The PI will actively participate in journal clubs and symposia and present abstracts at national meetings, as well as submit manuscripts to top peer-reviewed journals.
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ketones, Muscle Metabolism, and SGLT2 Inhibitors
- ClinicalTrials.gov ID
- NCT06229678
- Acronym / sponsor ID
- STUDY00000012
- Keywords
- ketones, cardiovascular benefit
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 71 participants (estimated)
- Lead sponsor
- The University of Texas Health Science Center at San AntonioUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 25 Jan 2024 (actual)
- Primary completion
- 1 Nov 2026 (estimated)
- Study completion
- 1 Mar 2027 (estimated)
- First posted
- 29 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study team will examine the effects of elevated plasma ketone levels following initiation of SGLT2 inhibitor therapy in high-risk type 2 diabetes mellitus (T2DM) individuals with heart failure (HF) with reduced ejection fraction (HFrEF) providing an energy-rich fuel that is taken up with great avidity by the myocardium, to measure change in Left Ventricle diastolic and systolic function
Detailed description
The study team will examine the effects of elevated plasma ketones caused by 12-week treatment with an SGLT2i (empagliflozin) treatment in participants with T2DM and HF. The study team will focus on three possible mechanisms of action for these effects and test the following:
(i) Skeletal muscle bioenergetics. Using 31P-MRS, the team will quantify phosphocreatine [PCr], ATP, inorganic phosphate, phosphodiester, and intracellular pH. With 1H-MRS, and will measure intramyocellular lipid content at rest and ATPmax production after exercise. The team will examine the relationships between phosphorous metabolite concentrations, intramyocellular lipid content, and ATP generation before and after 12 weeks of SGLT2 inhibition.
(ii) LV systolic and diastolic function using cardiac MRI in type 2 diabetic patients with Class II-III NYHA heart failure and reduced EF.
(iii) To examine the contribution of the SGLT2i-induced increase in plasma ketone concentration on myocardial function and myocardial blood flow by inhibiting the rise in plasma ketone concentration with acipimox while continuing empagliflozin.
(iv) Improvements in Patient-Reported Outcomes (PRO). Kansas City Cardiomyopathy Questionnaire ( KCCQ) scoring will be used to evaluate self-reported physical function and well-being. This tool is a well-developed and validated method to obtain patient self-reported parameters of health in adults.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- A randomized (2:1) placebo controlled double blind study
| Arm | Type | Receives |
|---|---|---|
| Empagliflozin Group | Experimental | Drug: Empagliflozin 25 MG Oral Tablet, Drug: Acipimox 250 Mg Oral CapsuleSubjects will be randomized 2:1 to receive empagliflozin, 25mg/day for 3 months |
| Placebo group | Placebo comparator | Drug: Placebo, Drug: Acipimox 250 Mg Oral CapsuleSubjects will be randomized to receive the empagliflozin placebo for 3 months |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Type 2 Diabetes Mellitus
- Class II-III New York Heart Association (NYHA) heart failure and reduced ejection fraction (EF) <50%
- Age 18-80 years
- BMI 23-44 kg/m2
- Glycated hemoglobin (HbA1c) 6.0-10.0%
Key exclusion criteria (8 listed)
- Heart failure due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, severe valvular heart disease, hypertrophic obstructive cardiomyopathy.
- Significant change in diuretic management during the month prior to screening (defined by doubling of diuretic dose or addition of another heart failure medication)
- Type 2 Diabetics treated with Dipeptidyl Peptidase-4 Inhibitor (DPP4i) or pioglitazone
- Pregnancy, lactation, or plans to become pregnant. A negative pregnancy test will be performed before each MRI study to assess current status. For women of child-bearing age (WOCBA) willingness to use contraception, if applicable.
- Allergy/sensitivity to study drugs or their ingredients.
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 |
|---|---|---|
| Empagliflozin 25 MG Oral TabletAlso: jardianceEmpagliflozin 25MG will be administered orally once per day for 3 months | Drug | Empagliflozin Group |
| PlaceboThe placebo will be administered orally once per day for 3 months | Drug | Placebo group |
| Acipimox 250 Mg Oral Capsulesubjects will be started on acipimox 250mg every 6 hours for 8 days while on continued empagliflozin/placebo therapy. This will be added at the end of 3 months after they finished baseline studies | Drug | Empagliflozin Group, Placebo group |
Primary outcome
Change in Phosphocreatine
Time frame: Baseline to 3 months
A measure of phosphocreatine change from baseline to study end
Change in Adenosine Triphosphate (ATP)
Time frame: Baseline to 3 months
A measure of ATP change from baseline to study end
Change in Inorganic Phosphate
Time frame: Baseline to 3 months
A measure of inorganic phosphate change from baseline to study end
Change in Phosphodiester
Time frame: Baseline to 3 months
A measure of phosphodiester change from baseline to study end
ATPmax production
Time frame: Baseline to 3 months
Exercise induced ATPmax production change
6 secondary outcomes
Plasma Beta-hydroxybutyrate (β-OH-B)
Time frame: baseline to 3 months
Acetoacetate concentrations
Time frame: baseline to 3 months
6-min walking test
Time frame: baseline to 3 months
Patient-Reported Outcomes Measure Information System
Time frame: baseline to 3 months
plasma ketone concentration on myocardial function
Time frame: Baseline to 3months + 8 days
plasma ketone concentration on myocardial blood flow
Time frame: Baseline to 3months + 8 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2026.
- Individual participant dataSharing planned: Yes. The PI will actively participate in journal clubs and symposia and present abstracts at national meetings, as well as submit manuscripts to top peer-reviewed journals.
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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.
Ralph DeFronzo, MD principal investigator
The University of Texas Health Science Center at San Antonio
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Empagliflozin 25 MG Oral Tablet and Acipimox 250 Mg Oral Capsule in people with Type2diabetes and Heart Failure With Reduced Ejection Fraction, run by The University of Texas Health Science Center at San Antonio at 1 site 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 10 inclusion and 8 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: looking for participants now, as of the sponsor's last update on 5 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ralph DeFronzo, MD (210-567-6691, defronzo@uthscsa.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Phosphocreatine (time frame: Baseline to 3 months). The study lists 5 primary outcomes in all. 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 Feb 2026.