Beta-hydroxybutyrate for Type 2 Diabetes
(Protocol1 Trial)
Recruiting in Palo Alto (17 mi)
+1 other location
Overseen byRalph A DeFronzo, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: The University of Texas Health Science Center at San Antonio
Must not be taking: GLP-1 RA, DPP4i, Pioglitazone, Insulin
Disqualifiers: Pregnancy, Breastfeeding, MRI contraindications, others
No Placebo Group
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?To examine the effect of an increase in plasma beta-hydroxy-butyrate (B-OH-B) levels, spanning the physiologic and pharmacologic range (+0.5, +2.0, and +5.0 mmol/L), on: (i) parameters of left ventricular (LV) systolic and diastolic function utilizing cardiac magnetic resonance imaging (MRI) and (ii) myocardial glucose uptake using positron emission tomography (PET) with 18F-fluoro-2-deoxy-D-glucose in type 2 diabetic patients with Class II-III New York Heart Association (NYHA).
Will I have to stop taking my current medications?
If you are taking medications like GLP-1 RA, DPP4i, pioglitazone, SGLT2 inhibitors, or insulin, you will need to stop them to participate in this trial. The protocol does not specify about other medications, so it's best to discuss with the trial team.
What data supports the effectiveness of the drug Beta-hydroxybutyrate, Farxiga, dapagliflozin for Type 2 Diabetes?
Dapagliflozin (Farxiga) is effective in treating type 2 diabetes by lowering blood sugar levels and is also approved to reduce the risk of kidney and heart problems in people with chronic kidney disease. It works by helping the kidneys remove sugar from the body through urine, and it has been shown to be effective and generally well-tolerated in numerous clinical trials.
12345Is dapagliflozin (Farxiga) safe for humans?
Dapagliflozin (Farxiga) is generally considered safe for humans, with clinical trials showing it is well tolerated. Common side effects include genital and urinary tract infections, but it does not cause serious issues like liver or kidney damage. It is not recommended for people with moderate or severe kidney problems.
34567How is the drug dapagliflozin unique in treating type 2 diabetes?
Dapagliflozin is unique because it works by blocking a protein in the kidneys called SGLT2, which helps remove excess sugar from the body through urine, and it does this without relying on insulin. This makes it a good option for people who need additional help managing their blood sugar levels alongside other diabetes medications.
12345Eligibility Criteria
This trial is for adults aged 18-80 with Type 2 diabetes and heart failure (Class II-III NYHA) who have an ejection fraction below 50%. Participants should have a BMI of 23-38, stable blood pressure, and specific levels of HbA1c and NT-proBNP. Those on certain diabetes medications or with conditions that could risk safety or affect results can't join.Inclusion Criteria
Your body mass index (BMI) is between 23 and 38.
My heart's pumping ability is reduced, and I have some limitations on physical activity.
Your HbA1c level is between 6.0% and 9.0%.
+5 more
Exclusion Criteria
I am not pregnant or breastfeeding.
Any other condition that in the opinion of the investigator create a hazard to the subject safety, endanger the study procedures or interfere with the interpretation of study results
I am currently taking medication for diabetes.
+1 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Baseline Assessment
Baseline cardiac MRI and blood samples are taken to measure cardiac functional parameters and various biomarkers
1 day
1 visit (in-person)
Treatment
Participants receive a prime-continuous infusion of racemic B-OH-B to increase plasma B-OH-B concentration, followed by MRI and PET studies
1 day
1 visit (in-person)
Follow-up
Participants return for a repeat PET/18F-2-DOG study to examine the effect of hyperketonemia on myocardial glucose uptake and blood flow
14 days
1 visit (in-person)
Participant Groups
The study tests how different levels of beta-hydroxy-butyrate (B-OH-B), a ketone body, affect heart muscle function and sugar uptake in the heart using advanced imaging techniques like cardiac MRI and PET scans in people with Type 2 diabetes suffering from heart failure.
3Treatment groups
Active Control
Group I: Group I Beta-Hydroxy-ButyrateActive Control1 Intervention
Administration of beta-hydroxy-butyrate at 0.4 mg/kg.min for 20 minutes and then at a constant rate of 0.2 mg/kg.min until study end
Group II: Group II Beta-Hydroxy-ButyrateActive Control1 Intervention
Administration of beta-hydroxy-butyrate at 1.5 mg/kg.min for 20 minutes and then at a constant rate of 0.75 mg/kg.min until study end
Group III: Group III Beta-Hydroxy-ButyrateActive Control1 Intervention
Administration of beta-hydroxy-butyrate at 4.0 mg/kg.min for 20 minutes and then at a constant rate of 2.0 mg/kg.min until study end
Beta-hydroxy-butyrate is already approved in European Union, United States, Japan for the following indications:
🇪🇺 Approved in European Union as Farxiga for:
- Type 2 diabetes
🇺🇸 Approved in United States as Farxiga for:
- Type 2 diabetes
- Heart failure
🇯🇵 Approved in Japan as Forxiga for:
- Type 2 diabetes
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Texas Diabetes Institute - University Health SystemSan Antonio, TX
University of Texas Health Science Center San AntonioSan Antonio, TX
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Who Is Running the Clinical Trial?
The University of Texas Health Science Center at San AntonioLead Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Collaborator
References
Pharmacokinetics, pharmacodynamics and clinical efficacy of dapagliflozin for the treatment of type 2 diabetes. [2021]Dapagliflozin (DAPA) (Farxiga or Forxiga) is a sodium glucose cotransporter 2 (SGLT2) inhibitor approved for type 2 diabetes mellitus(T2DM) treatment.
Selective reaction monitoring of negative electrospray ionization acetate adduct ions for the bioanalysis of dapagliflozin in clinical studies. [2021]Dapagliflozin (Farxiga), alone, or in the fixed dose combination with metformin (Xigduo), is an orally active, highly selective, reversible inhibitor of sodium-glucose cotransporter type 2 (SGLT2) that is marketed in United States, Europe, and many other countries for the treatment of type 2 diabetes mellitus. Here we report a liquid chromatography-tandem mass spectrometry (LC-MS/MS) bioanalytical assay of dapagliflozin in human plasma. A lower limit of quantitation (LLOQ) at 0.2 ng/mL with 50 μL of plasma was obtained, which reflects a 5-fold improvement of the overall assay sensitivity in comparison to the previous most sensitive assay using the same mass spectrometry instrumentation. In this new assay, acetate adduct ions in negative electrospray ionization mode were used as the precursor ions for selective reaction monitoring (SRM) detection. Sample preparation procedures and LC conditions were further developed to enhance the column life span and achieve the separation of dapagliflozin from potential interferences, especially its epimers. The assay also quantifies dapagliflozin's major systemic circulating glucuronide metabolite, BMS-801576, concentrations in human plasma. The assay was successfully transferred to contract research organizations (CROs), validated, and implemented for the sample analysis of pediatric and other critical clinical studies. This assay can be widely used for bioanalytical support of future clinical studies for the newly approved drug Farxiga or any combination therapy containing dapagliflozin.
Dapagliflozin: a review of its use in patients with type 2 diabetes. [2022]Dapagliflozin (Forxiga(®), Farxiga(®)) is an orally administered sodium-glucose co-transporter-2 (SGLT2) inhibitor used in the management of patients with type 2 diabetes. Dapagliflozin reduces renal glucose reabsorption by inhibiting the transporter protein SGLT2 in the renal proximal tubule, thereby increasing urinary glucose excretion and reducing blood glucose levels. Its mechanism of action is independent of insulin secretion or action; therefore, dapagliflozin provides complementary therapy when used in combination with other antihyperglycaemic drugs. This article updates an earlier review of dapagliflozin and focuses on longer-term efficacy and tolerability data (e.g. from extensions of earlier clinical trials), as well as data from studies in special patient populations (e.g. history of cardiovascular disease). Numerous well-designed clinical trials with dapagliflozin, primarily as add-on therapy for 24 weeks (but also as monotherapy or initial combination therapy), have consistently demonstrated reductions in glycosylated haemoglobin, fasting plasma glucose levels and bodyweight. Extensions of these trials show the effects are maintained over longer-term follow-up periods of ≈1-4 years and dapagliflozin is generally well tolerated. Dapagliflozin has a low risk of hypoglycaemia, although the incidence varies depending on background therapy, and genital mycotic infections (particularly in women) are the most common adverse events. Dapagliflozin is not recommended in patients with moderate or severe renal impairment. In view of its unique mechanism of action and now well-established efficacy and tolerability profile, dapagliflozin is a useful treatment option in the management of type 2 diabetes, although its effects on diabetic complications remain to be evaluated.
Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus. [2021]To review clinical evidence for the efficacy, safety, and tolerability of dapagliflozin (Farxiga-AstraZeneca), a sodium glucose cotransporter 2 inhibitor, as monotherapy or in combination with other hypoglycemic agents for the treatment of type 2 diabetes.
Antidiabetic Drug Approved to Reduce Risk of Kidney Disease. [2023]Dapagliflozin (Farxiga) is now approved to reduce the risk of declining kidney function, kidney failure, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease with or without type 2 diabetes.
Dapagliflozin no longer licensed for type 1 diabetes. [2022]Overview of: Medicines and Healthcare products Regulatory Agency. Dapagliflozin (Forxiga): no longer authorised for treatment of type 1 diabetes mellitus. Drug Safety Update 2021;15:3.
Dapagliflozin: a novel sodium-glucose cotransporter type 2 inhibitor for the treatment of type 2 diabetes mellitus. [2021]The prevalence of diabetes mellitus has grown to staggering numbers, and its incidence is expected to rise in the next 2 decades. The need for novel approaches to treat hyperglycemia cannot be ignored. Current agents have been shown to modestly improve glycemia and in some cases prevent complications of diabetes, but they become less effective over time and are often accompanied by undesirable adverse effects. Dapagliflozin is the lead agent in a new class of oral antidiabetic agents known as sodium-glucose cotransporter type 2 (SGLT2) inhibitors, which represent a novel approach to the management of type 2 diabetes mellitus. By selectively and reversibly blocking the SGLT2 receptor, dapagliflozin prevents the reabsorption of glucose at the renal proximal tubule. Phase II and III clinical trials have demonstrated that dapagliflozin is a safe and effective method for treating type 2 diabetes. Dapagliflozin produces a sustained, dose-dependent reduction in plasma glucose levels while simultaneously improving insulin secretion and sensitivity. Over 12-24 weeks, reductions in hemoglobin A(1c) ranged from 0.54-0.89% when dapagliflozin was administered once/day (either as monotherapy or add-on therapy to oral antidiabetic drugs with or without insulin) to patients with type 2 diabetes. Therapy with dapagliflozin also results in a mild osmotic-diuretic effect that may account for decreases in total body weight (~2-3 kg) and blood pressure (systolic 2-5 mm Hg, diastolic 1.5-3 mm Hg), and increases in hematocrit (1-2%). Dapagliflozin has a favorable safety profile, with the rates of hypoglycemia similar to those of placebo. Genital and urinary tract infections were more commonly reported in patients taking dapagliflozin (2-13%) than those taking placebo (0-8%). Dapagliflozin does not appear to cause electrolyte disturbances, hepatotoxicity, or nephrotoxicity. Results from clinical trials have been promising, and well-designed clinical programs that address the long-term safety and efficacy of dapagliflozin are under way.