Sodium-glucose Co Transporter 2 (sGLT2) Inhibitor and Endogenous Ketone Production
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|ClinicalTrials.gov Identifier: NCT03852901|
Recruitment Status : Recruiting
First Posted : February 25, 2019
Last Update Posted : December 20, 2019
The drug Jardiance treats diabetes. It lowers blood sugar by increasing glucose the kidneys excrete. This increases levels of ketones formed in the blood. The body makes ketones when it does not have enough glucose for fuel. The brains of many people with age-related diseases like Alzheimer s do not use glucose well. Brain use of ketones might improve mental ability. Researchers want to see how Jardiance affects ketone levels, which could lead to ways to improve brain health as people age.
To study how taking Jardiance affects ketone levels in people without diabetes.
Adults at least 55 years old without diabetes
Participants will fast before all visits and sometimes during visits. Snacks or meals will be provided.
Participants will be screened with medical history, physical exam, and blood tests.
At 3 study visits over about 4 weeks, participants will:
Have a thin plastic tube inserted in an arm vein for frequent blood samples
Have their urine collected throughout the visit
Write what they eat and when in a diary
Answer questions about symptoms
Have an MRI/MRS scan. A strong magnetic field and radio waves will take pictures of the brain and measure its blood flow and function. Participants will lie on a table that slides into the scanner. They will wear a plastic device on their head and earplugs.
Participants will take the study drug once a day for 2 weeks.
Participants will get an activity monitor and walk about 2,000 steps most evenings.
A small sensor will be inserted in participants upper arm for 4 weeks to measure blood glucose.
Participants will have a follow-up phone call.
|Condition or disease||Intervention/treatment||Phase|
|Empaglifozin Physiological Effects of Drugs Hypoglycemic Agents Sodium-Glucose Transporter 2 Inhibitors||Drug: Jardiance 25 mg||Phase 1|
Objective and Specific Aims: The objective of this proof-of-concept study is to demonstrate in non-diabetic men and women age > 55 years that a sGLT2 inhibitor will increase ketone bodies and metabolites used for gluconeogenesis. We also hypothesize that sGLT2 inhibitor (empagliflozin) will increase circulating glucagon and fatty acids, decrease circulating amino acids, increase expression of receptors and mediators of ketone metabolism in plasma exosomes and change Magnetic Resonance Spectroscopy (MRS) brain metabolism measures.
Experimental Design and Methods: 10 men and 10 women will be recruited for this pilot study. Each eligible participant will have a screen visit (Visit 0) and three additional 2-day study visits (Visit 1-3). On Visits 1, 2 and 3, frequent blood sampling for Beta-hydroxybutyrate butyrate (Beta-OHB), acetoacetate, fatty and amino acids, glucagon, insulin and glucose levels will be carried out; these visits will also include blood work for exosome markers and brain MRS. In addition, placement of a continuous glucose monitor (CGM) along with a 34-hour urine collection will be carried out. On Visits 1 and 2 the participants will wear the CGM until they return for their next visit. On Visit 3 the CGM will be removed at the end of the study visit. On Visit 1, no empagliflozin will be administered. Participants will return in 13 +/- 2 days for Visit 2. Visit 2 is the same as Visit 1 except empagliflozin 25 mg will be administered both mornings, at least 30 minutes before eating breakfast and participants will continue empagliflozin 25 mg once every morning, at least 30 minutes before eating breakfast, at home until they return in 13 +/- 2 days for Visit 3. At the end of Visit 3, empagliflozin will be stopped.
Medical Relevance and Expected Outcome: Elevating ketone bodies may bolster neuronal health and delay onset and progression of cognitive impairment. The expected outcome of this study is that we will see an increase in circulating levels of ketones, glucagon and fatty acids, an increased expression of receptors and mediators of ketone metabolism in plasma exosomes and a change in Magnetic Resonance Spectroscopy (MRS) brain metabolism measures, in subjects taking a sGLT2 inhibitor. We expect circulating amino acid levels will decrease, especially during the overnight hours. This study will aid in deciding whether this class of compound may be used in a larger study to improve cognitive function in patients with diagnosis consistent with declining cognitive function. We require that empagliflozin be taken for up to 2 weeks before returning for Visit 3, because we need to fully understand the homeostatic adaptations that may occur in the metabolite response to empagliflozin due to prolonged (up to 2 weeks) sGLT2 inhibition. It is our goal in the future to use the information gathered in this pilot study to design a long-term study in people who actually suffer from mild cognitive impairment/AD and therefore a Visit 2 (34-hour acute study) only, as outlined above, would not give us the full picture of the metabolic changes that might occur with prolonged use, especially in a non-diabetic population.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||100 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Sodium-Glucose CoTransporter 2 (sGLT2) Inhibitor and Endogenous Ketone Production|
|Actual Study Start Date :||March 28, 2019|
|Estimated Primary Completion Date :||December 31, 2022|
|Estimated Study Completion Date :||December 31, 2022|
Experimental: Single Arm
Drug: Jardiance 25 mg
This study involves a screening visit (Visit 0) and 3 study visits (Visits 1, 2 and 3) to the NIA Clinical Unit. In this pilot study, each enrolled participant will have a baseline visit (Visit 1)where no medication will be given and frequent blood draws for 34 hours
- Elevating ketone bodies may bolster neuronal health and delay onset and progression of cognitive impairment. [ Time Frame: One year ]Expected outcome of this study is that we will see an increase in circulating levels of ketones, glucagon, and fatty acids, an increased expression of receptor and mediators of ketone metabolism in plasma exosomes and a change in MRS brain metabolism measures in subject taking a sGLT2 inhibitor.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03852901
|Contact: Denise L Melvin, R.N.||(410) email@example.com|
|United States, Maryland|
|National Institute on Aging, Clinical Research Unit||Recruiting|
|Baltimore, Maryland, United States, 21224|
|Principal Investigator:||Josephine M Earley, M.D.||National Institute on Aging (NIA)|