Sodium-glucose Co Transporter 2 (sGLT2) Inhibitor and Endogenous Ketone Production

• Status: Recruiting
• Trial end date: 2022-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Background:

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.

Objectives:

To study how taking Jardiance affects ketone levels in people without diabetes.

Eligibility:

Adults at least 55 years old without diabetes

Design:

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: National Institute on Aging (NIA)
• Treatments: Empagliflozin

Criteria

• INCLUSION CRITERIA:

• Age 55 years and older.

• Healthy (see exclusion criteria below).

• Able to understand the study risks and procedures, and consent to participate in the study.

• Able to read and speak English.

EXCLUSION CRITERIA (SCREENING VISIT):

• History of diabetes (requiring any medical treatment other than diet and exercise) or fasting plasma glucose > 126 mg/dl or HbA1c> 6.5 %.

• History of hypoglycemia.

• BMI > 35 kg/m(2).

• Creatinine clearance less than 60 ml/min as measured by GFR.

• Glucosuria

• History of anemia within the past 6 months or Hgb <11.0 mg/dL for women and Hgb <12.5 mg/dL for men.

• Current steroid use or steroid use within 90 days of screening, excluding eye drops.

• Currently taking loop diuretics (Lasix, for example).

• Participant presently following a calorie restriction diet, low carb/high fat diet.

• HIV virus infection

• Hepatitis B infection, as evidenced by a positive HBsAG at screen visit.

• Hepatitis C infection that has not been treated. (The screen blood work must show HCV RNA quantitative is not detectable).

• Active infection/fever that may cause changes in glucose metabolism.

• Known allergy to sGLT2 inhibitors in the past.

• Thyroid dysfunction that is not controlled or treated. This will be determined by Free T3, T4, Free T4 or TSH not within MedStar Harbor Hospital laboratory normal ranges for this pilot study.

• Adrenal dysfunction as determined by a cortisol level not within the normal range for MedStar Harbor Hospital Laboratory for this pilot study.

• Kidney or liver disease, (GFR < 60 mL/min/1.73 m(2) and/or liver enzymes not within normal ranges for MedStar Harbor Hospital Laboratory for this pilot study.

• Severe gastrointestinal diseases such as Crohn s disease or ulcerative colitis requiring continuous treatment.

• History of severe pulmonary disease such as chronic obstructive pulmonary disease (COPD) or asthma requiring continuous medication use.

• Patients with known, or evidence of, peripheral vascular disease.

• History of chronic urinary tract infections.

• History of recurrent or recent dehydration in the past year.

• History of recurrent or recent vaginal yeast infection.

• Alcohol intake greater than 30 grams (drink more than 2 beers OR equivalent per day).

• History of severe psychiatric conditions associated with behavioral problems or requiring chronic medical treatment.

• Poor venous access.

• Inability to walk 2,000 steps

• Donation or loss of 400 mL or more of blood within 56 days prior to and subsequent to screening.

• Participation in another study in the past 30 days, in which a study drug was administered.

• Currently participating in another study unless the investigator feels it would not interfere with the study.

• History of a medical condition or any other reason that, in the opinion of the investigator, will make participation in this study unsafe.

• Blood work or urine tests that are not considered by the study physician to be in an acceptable range for the study.

• Metal implants and devices incompatible with 3T Magnetic Resonance Imaging (MRI), or another contraindication to MRI.