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

NCT03852901 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 19006019-AG-0060
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

Background: The drug empagliflozin 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. We investigated how empagliflozin affects ketone levels, which could lead to ways to improve brain health as people age. Objectives: To study how taking empagliflozin affects systemic and brain metabolism including ketone levels in people without diabetes. Eligibility: Adults at least 55 years old without diabetes Design: After a screening Visit, eligible participants were admitted to the NIA Clinical Unit during Visits 1 (baseline), 2 (first dose) and 3 (last/14th dose). On each Visit, blood draws were performed and circulating metabolites and hormones were repeatedly measured over 34-hour periods. Using plasma from fasting state only, we isolated total and neuronal-origin extracellular vesicles to measure proteins of the IGF-1 and insulin signaling cascades. Furthermore, on each Visit, we performed magnetic resonance spectroscopy (MRS) to measure concentrations of a plethora of metabolites in the brain. Between Visits 2 and 3, participants were taking the drug at home. A continuous glucose monitoring device was placed to detect potential glucose fluctuations while at home. The study was concluded for participants after the end of Visit 3.

Conditions

Empaglifozin; Physiological Effects of Drugs; Hypoglycemic Agents; Sodium-Glucose Transporter 2 Inhibitors

Keywords

Ketones; Metabolism; Hormones; Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

• Change in Serum β-hydroxybutyrate (BHB)

  Change in serum β-hydroxybutyrate (BHB) after 14 days on empagliflozin, compared with baseline.

  14 days

Secondary Outcomes (7)

• Change in Plasma Glucose

  14 days

• Change in Serum Non-esterified Fatty Acids (NEFAs)

  14 days

• Change in Plasma Insulin

  14 days

• Change in Serum Acetoacetate (AcAc)

  14 days

• Change in 1H MRS BHB

  14 days

Study Arms (1)

Single Arm

EXPERIMENTAL

Single group

Drug: empagliflozin (Jardiance) 25 mg

Interventions

empagliflozin (Jardiance) 25 mg DRUG

Oral empagliflozin 25 mg/day x 14 days

Single Arm

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 55 years and older.

You may not qualify if:

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

Sponsors & Collaborators

• National Institute on Aging (NIA): lead

Study Sites (1)

National Institute on Aging, Clinical Research Unit

Baltimore, Maryland, 21224, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Ketosis; Alzheimer Disease

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Josephine M. Egan, MD, Clinical Director
• Organization: National Institute on Aging

eganj@mail.nih.gov

410-558-8414

Study Officials

• Josephine M Egan, M.D.

  National Institute on Aging (NIA)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2019
• First Posted: February 25, 2019
• Study Start: March 28, 2019
• Primary Completion: November 12, 2020
• Study Completion: December 13, 2021
• Last Updated: August 2, 2022
• Results First Posted: August 2, 2022

Record last verified: 2021-12-13

Locations

US (1)