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Use of Empagliflozin to Treat Prediabetes

Primary Purpose

PreDiabetes, Prediabetic State, Overweight and Obesity

Status

Recruiting

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Empagliflozin

Multivitamin-Placebo

About this trial

This is an interventional basic science trial for PreDiabetes

Eligibility Criteria

18 Years - 59 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

BMI 26-45 kg/m2
Weight stable (± 2 kg in previous 6 months)
Prediabetes:
fasting blood glucose 100-125 mg/dL, or
2-hour plasma glucose 140-199 mg/dL after 75 g glucose load, or
HbA1c 5.7-6.4% (39-47 mmol/mol)

Exclusion Criteria:

Regular moderate-vigorous exercise (≥30 min/session on ≥2 days per week)
Pregnancy, planning to become pregnant or nursing
Lidocaine allergy
Current or recent smoking or nicotine use (≤ 1-year abstention)
Medications including glucose lowering medications and supplements (SGLT2 inhibitors, GLP1 agonists, sulfonylurea, insulin, TZDs); mono-amine oxidase inhibitors; beta-blockers; diuretics
Major metabolic or cardiovascular conditions (e.g., type 1 diabetes, Crohn's disease, untreated hypo- or hyperthyroid, cancer, coronary artery disease, tachycardia, prior bariatric surgery, peripheral vascular disease, liver diseases (e.g., cirrhosis)
Type 2 diabetes:
fasting blood glucose ≥126 mg/dL, or
2-hour plasma glucose ≥200 mg/dL after 75 g glucose load, or
HbA1c ≥6.5% (48 mmol/mol)
Contraindications/precautions for empagliflozin (impaired renal function (EGR<60), history of: empagliflozin hypersensitivity, ketoacidosis, hypotension, recurring urinary tract or genital mycotic infections, amputation)

Sites / Locations

Oregon State UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Empagliflozin

Multivitamin-Placebo

Arm Description

Participants will be provided 10-25mg empagliflozin per day for 13 weeks.

Participants will be provided 1 multivitamin-placebo per day for 13 weeks.

Outcomes

Primary Outcome Measures

Insulin-stimulated glucose disposal

The glucose infusion rate to maintain glycemia during insulin clamp, using plasma enrichment of glucose isotope tracer to determine changes in rates of insulin-stimulated glucose disposal

Secondary Outcome Measures

Oral glucose tolerance

The change in blood glucose concentration in response to a 75g glucose beverage

Fasting plasma glucose concentration

The change in fasting plasma glucose concentration

Whole-body fat oxidation

Indirect calorimetry will be used to determine the change in whole-body rate of fat oxidation during basal and insulin-stimulated conditions

Skeletal muscle insulin signaling

Immunoblotting to determine the change in activation of insulin signaling proteins in skeletal muscle collected at basal and during insulin-stimulated conditions

Skeletal muscle lipids

Mass spectrometry lipidomic analysis of skeletal muscle to determine changes in muscle lipid content

Skeletal muscle mitochondrial respiratory function

Changes in skeletal muscle mitochondrial respiratory capacity measured using high-resolution respirometry

Skeletal muscle energetic stress

Immunoblotting to determine changes in activation of AMPK and related signaling proteins pathways

Full Information

NCT ID

NCT05426525

First Posted

June 8, 2022

Last Updated

June 26, 2023

Sponsor

Oregon State University

Collaborators

Samaritan Health Services

1. Study Identification

Unique Protocol Identification Number

NCT05426525

Brief Title

Use of Empagliflozin to Treat Prediabetes

Official Title

Use of Empagliflozin to Treat Prediabetes - a Randomized, Double-blind, Placebo-controlled 13-week Intervention Trial

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 13, 2022 (Actual)

Primary Completion Date

April 2025 (Anticipated)

Study Completion Date

April 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Oregon State University

Collaborators

Samaritan Health Services

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The overall purpose of this study is to identify how empagliflozin (a drug commonly used to treat type 2 diabetes) impacts skeletal muscle metabolic health among adults with prediabetes. Our aims are to: 1) Test the ability of empagliflozin to improve regulation of glucose metabolism (i.e., blood sugar) among overweight and obese individuals at risk for diabetes, and 2) Identify mechanisms to explain how empagliflozin may improve skeletal muscle glucose metabolism. We hypothesize empagliflozin will improve regulation of glucose metabolism due to changes in whole-body and skeletal muscle metabolism (e.g., increased rates of whole-body fat oxidation, evidence of impaired skeletal muscle mitochondrial respiratory function and increased energetic stress, lower accumulation of skeletal muscle lipids and improved skeletal muscle insulin signaling compared with placebo treatment).

Detailed Description

The overall study design is a 13-week, double-blind, placebo-controlled intervention trial, testing the ability of empagliflozin to improve glucose metabolism among overweight and obese individuals at risk for diabetes (compared with a multivitamin-placebo). The study involves metabolic testing before and during the intervention to identify changes in outcomes as a function of the intervention and to ensure participant safety. The study involves 9 visits to the Samaritan Athletic Medicine Center on the campus of Oregon State University in Corvallis, Oregon. Full completion of the study is anticipated to take ~4 months. The project is being completed in collaboration with physicians at Samaritan Health Services.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

PreDiabetes, Prediabetic State, Overweight and Obesity

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Pills will be prepared and dispensed by a pharmacy to blind participants and investigators.

Allocation

Randomized

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Empagliflozin

Arm Type

Experimental

Arm Description

Participants will be provided 10-25mg empagliflozin per day for 13 weeks.

Arm Title

Multivitamin-Placebo

Arm Type

Placebo Comparator

Arm Description

Participants will be provided 1 multivitamin-placebo per day for 13 weeks.

Intervention Type

Drug

Intervention Name(s)

Empagliflozin

Other Intervention Name(s)

Jardiance

Intervention Description

Participants will take 10mg empagliflozin per day for 2 weeks. Absent contraindications, dosing will be increased to 25 mg empagliflozin per day for the next 11 weeks.

Intervention Type

Drug

Intervention Name(s)

Multivitamin-Placebo

Intervention Description

Participants will take 1 multivitamin per day for 13 weeks.

Primary Outcome Measure Information:

Title

Insulin-stimulated glucose disposal

Description

The glucose infusion rate to maintain glycemia during insulin clamp, using plasma enrichment of glucose isotope tracer to determine changes in rates of insulin-stimulated glucose disposal

Time Frame

Insulin-stimulated glucose disposal is measured before the start of the intervention (baseline) and during week 13 of the intervention.

Secondary Outcome Measure Information:

Title

Oral glucose tolerance

Description

The change in blood glucose concentration in response to a 75g glucose beverage

Time Frame

Oral glucose tolerance is measured before the start of the intervention (baseline) and during week 12 of the intervention.

Title

Fasting plasma glucose concentration

Description

The change in fasting plasma glucose concentration

Time Frame

Fasting plasma glucose is measured before the start of the intervention (baseline) and during week 13 of the intervention.

Title

Whole-body fat oxidation

Description

Indirect calorimetry will be used to determine the change in whole-body rate of fat oxidation during basal and insulin-stimulated conditions

Time Frame

Whole-body fat oxidation is measured before the start of the intervention (baseline) and during week 13 of the intervention.

Title

Skeletal muscle insulin signaling

Description

Immunoblotting to determine the change in activation of insulin signaling proteins in skeletal muscle collected at basal and during insulin-stimulated conditions

Time Frame

Skeletal muscle insulin signaling is measured before the start of the intervention (baseline) and during week 13 of the intervention.

Title

Skeletal muscle lipids

Description

Mass spectrometry lipidomic analysis of skeletal muscle to determine changes in muscle lipid content

Time Frame

Skeletal muscle lipids are measured before the start of the intervention (baseline) and during week 13 of the intervention.

Title

Skeletal muscle mitochondrial respiratory function

Description

Changes in skeletal muscle mitochondrial respiratory capacity measured using high-resolution respirometry

Time Frame

Skeletal muscle mitochondrial respiratory function is measured before the start of the intervention (baseline) and during week 13 of the intervention.

Title

Skeletal muscle energetic stress

Description

Immunoblotting to determine changes in activation of AMPK and related signaling proteins pathways

Time Frame

Skeletal muscle energetic stress is measured before the start of the intervention (baseline) and during week 13 of the intervention.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

59 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: BMI 26-45 kg/m2 Weight stable (± 10 lbs in previous 3 months) Fasting blood glucose <126 mg/dL or HbA1c <6.5% (<48mmol/mol) Exclusion Criteria: Regular moderate-vigorous exercise (≥30 min/session on ≥2 days per week) Pregnancy, planning to become pregnant or nursing Lidocaine allergy Current or recent smoking or nicotine use (≤ 1-year abstention) Medications including glucose lowering medications and supplements (SGLT2 inhibitors, GLP1 agonists, sulfonylurea, insulin, TZDs); mono-amine oxidase inhibitors; beta-blockers; diuretics Major metabolic or cardiovascular conditions (e.g., type 1 diabetes, Crohn's disease, untreated hypo- or hyperthyroid, cancer, coronary artery disease, tachycardia, prior bariatric surgery, peripheral vascular disease, liver diseases (e.g., cirrhosis) Diagnosed type 2 diabetes. In absence of diagnosis, two separate samples with test results of fasting blood glucose ≥126 mg/dL or HbA1c ≥6.5% (48 mmol/mol). Contraindications/precautions for empagliflozin (impaired renal function (EGR<60), history of: empagliflozin hypersensitivity, ketoacidosis, hypotension, recurring urinary tract or genital mycotic infections, amputation)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Sean A Newsom, Ph.D.

Phone

(541) 737-1613

sean.newsom@oregonstate.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Matthew M Robinson, Ph.D.

Phone

(541) 737-1126

matthew.robinson@oregonstate.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sean A Newsom, Ph.D.

Organizational Affiliation

Oregon State University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Oregon State University

City

Corvallis

State/Province

Oregon

ZIP/Postal Code

97331

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sean A Newsom, Ph.D.

Phone

541-737-1613

sean.newsom@oregonstate.edu

First Name & Middle Initial & Last Name & Degree

Matthew M Robinson, Ph.D.

Phone

(541) 737-1126

matthew.robinson@oregonstate.edu

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

The current study is a pilot and feasibility project. IPD will not be made publicly available, save for publication and reporting requirements. Individual requests for data will be addressed by the Principal Investigator.

Learn more about this trial

Use of Empagliflozin to Treat Prediabetes

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