Low-Carb Diet + SGLT2 Inhibitor for Ketosis Management

(CASINO Trial)

Overseen By Recruitment Department

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: AdventHealth Translational Research Institute

Must be taking: SGLT2 inhibitors

Must not be taking: Psychiatric medications, Anti-diabetic agents

Disqualifiers: Cardiovascular disease, Diabetes, Hypertension, Infection, Kidney disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a low-carb diet combined with an SGLT2 inhibitor (a medication that lowers blood sugar levels) affects blood ketone levels. It examines whether this combination can help manage ketosis, a condition where the body burns fat instead of carbs for energy. The trial is open to generally healthy individuals who have maintained a stable weight for the past six months and can follow specific dietary guidelines. This research could lead to new methods for managing ketosis and improving metabolic health. As a Phase 1 trial, the focus is on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking advancements in metabolic health.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications that may influence metabolism, anti-diabetic agents, blood thinners, and chronic use of aspirin or other non-steroidal anti-inflammatory drugs. If you have recently changed your medication or dosage in the past 3 months, you may also be excluded.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining a low-carb diet with an SGLT2 inhibitor can sometimes lead to a rare condition called diabetic ketoacidosis (DKA). This condition occurs when the body produces too many ketones, chemicals made when fat is used for energy instead of sugar. However, very low-carb diets are generally safe and have low rates of DKA in individuals, regardless of whether they have type 2 diabetes.

SGLT2 inhibitors can lower the risk of serious problems, such as certain types of strokes, by about 50%, which is a significant benefit. Nonetheless, the risk of rare side effects like DKA should be considered and discussed with a healthcare provider. Weigh the benefits against the potential risks when considering participation in a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining a low-carbohydrate diet with an SGLT2 inhibitor for ketosis management because it offers a novel approach to addressing metabolic conditions. Most existing treatments focus on medication alone, but this combination leverages the natural effects of a low-carb diet to potentially enhance the body's ability to maintain healthy ketone levels. SGLT2 inhibitors, typically used to manage blood sugar in diabetes by promoting glucose excretion in urine, may also help facilitate ketosis more effectively when paired with dietary changes. This dual approach could provide more significant and synergistic benefits compared to using medication or diet alone, offering a promising new avenue for patients seeking better metabolic control.

What evidence suggests that this trial's treatments could be effective for ketosis management?

Research has shown that SGLT2 inhibitors can aid in weight loss and reduce body fat, which helps manage type 2 diabetes. In this trial, participants will receive a combination of SGLT2 inhibitors and a low-carb diet, enhancing the body's ability to burn fat for energy instead of carbohydrates. However, there is a rare risk of developing euglycemic diabetic ketoacidosis (euDKA), where acid levels in the blood increase even if blood sugar remains normal. Studies suggest that while low-carb diets are generally safe, close health monitoring is crucial when using them with SGLT2 inhibitors. Overall, this combination has shown promise in managing weight and improving health, but it requires careful management to avoid risks. ^{1 2 3 4 6}

Who Is on the Research Team?

Melissa Erickson, PhD

Principal Investigator

AdventHealth Translational Research Institute

Are You a Good Fit for This Trial?

Healthy volunteers aged 18-60 with a BMI of 21-35 kg/m2, who have been weight stable and are willing to follow the study's diet and procedures. Excluded are those with high blood pressure, liver disease, drug use, eating disorders, certain medical or psychiatric conditions, recent blood donation or medication changes that affect metabolism.

Inclusion Criteria

I am either male or female.

Willing and able to comply with scheduled visits, laboratory tests, and other study procedures

Otherwise healthy, as determined by medical history and laboratory tests

Exclusion Criteria

I am taking medication for diabetes.

I don't have health issues or take medications that would interfere with the study.

I have a condition that affects my blood's ability to clot or causes bleeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an SGLT2 inhibitor combined with a low-carbohydrate adaptive diet to achieve moderate ketosis

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Low-Carbohydrate Diet
• SGLT2 inhibitor

Trial Overview The trial is exploring how a low-carbohydrate diet paired with an SGLT2 inhibitor affects ketone levels in the blood. Participants will adapt to this controlled diet to induce moderate ketosis under close observation.

How Is the Trial Designed?

Group I: Single, Experimental Group Experimental Treatment 2 Interventions

SGLT2i + adaptive study diet of progressive dietary carbohydrate reduction

Who Is Running the Clinical Trial?

AdventHealth Translational Research Institute

Lead Sponsor

Trials

51

Recruited

5,900+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8998359/

The Use of SGLT-2 Inhibitors Coupled With a Strict Low- ... Literature investigation revealed that a strict low carbohydrate diet can rarely lead to DKA in the setting of SLGT-2 inhibitor use.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10672595/

The Ketogenic Effect of SGLT-2 Inhibitors—Beneficial or ... Weight loss → a ketogenic diet can lead to significant weight loss, and SGLT-2 inhibitors have been shown to reduce body weight and body fat. Cardiovascular ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2376060520310105

Euglycemic Diabetic Ketoacidosis Caused by SGLT2 ... We describe 2 patients with T2DM who developed euDKA caused by SGLT2 inhibitor use while on a ketogenic diet and provide a review of the literature.

4. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.16252

Illnesses associated with ketosis including diabetic ... Very low carbohydrate ketogenic diets are generally safe with low rates of IAK, including DKA, in people with and without type 2 diabetes.

5. endocrinologydiabetes.org endocrinologydiabetes.org/article/S2376-0605(20)30638-6/fulltext

Successful Reimplementation Of A Very Low Carbohydrate ... We report a case of a successful reimplementation of a very low carbohydrate ketogenic diet (VLCKD) after a case of euglycemic diabetic ketoacidosis (euDKA).

6. edm.bioscientifica.com edm.bioscientifica.com/view/journals/edm/2023/4/EDM23-0086.xml

A low-carbohydrate diet in place of SGLT2i therapy in a ... Summary. In patients with diabetes mellitus, the toxic milieu caused by abnormal glucose and free fatty acid handling can lead to heart failure (HF).