NCT02833415

Brief Summary

This study is a clinical study to investigate the gluconeogenesis pathway related to visceral adipose tissue (VAT) in obese individuals without type 2 diabetes and the effects of empagliflozin (EMPA) on glucose homeostasis in viscerally-obese individuals using functional studies of glycerol metabolism in hepatic gluconeogenesis using a well-validated nuclear magnetic resonance (NMR) spectroscopy platform.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Mar 2016

Typical duration for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2016

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

July 5, 2016

Completed
9 days until next milestone

First Posted

Study publicly available on registry

July 14, 2016

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2018

Completed
10 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2018

Completed
6 months until next milestone

Results Posted

Study results publicly available

May 2, 2019

Completed
Last Updated

January 23, 2020

Status Verified

January 1, 2020

Enrollment Period

1.8 years

First QC Date

July 5, 2016

Results QC Date

February 26, 2019

Last Update Submit

January 22, 2020

Conditions

Obesity, Visceral

Keywords

VisceralObesityAdiposeDiabetes

Outcome Measures

Primary Outcomes (1)

  • Change in Glycerol Enrichment

    \[U-13C3\] glycerol enrichment in plasma blood glucose over time will be measured by nuclear magnetic resonance spectroscopy. This is a percentage change from baseline to follow up in the percent enrichment of exogenous glycerol in blood glucose. We are unable to report a measure of central tendency and dispersion as the outcome is a percent change in the area under the enrichment curve for each group between baseline and follow-up. There is no measure of central tendency for these measurements without bootstrapping, which was not performed.

    3 months

Study Arms (2)

Empagliflozin

EXPERIMENTAL

Empagliflozin 10 mg by mouth daily for 3 months.

Drug: [U-13C3] glycerolDrug: Empagliflozin

Placebo

PLACEBO COMPARATOR

Placebo one tablet daily for 3 months

Drug: [U-13C3] glycerolDrug: Placebo (for Empagliflozin)

Interventions

[U-13C3] glycerolDRUG

Ingestion of \[U-13C3\] glycerol based on human's body weight such as (50 mg/kg body weight).

Also known as: Glycerine, Glycerin
EmpagliflozinPlacebo
EmpagliflozinDRUG

Active drug

Also known as: EMPA, Jardiace
Empagliflozin
Placebo (for Empagliflozin)DRUG

Placebo tablet manufactured to mimic EMPA 10 mg tablet.

Also known as: Placebo, Sugar pill
Placebo

Eligibility Criteria

Age30 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Obese, defined as BMI ≥ 30 kg/m2, at both time of abdominal fat imaging and at study entry.
  • Ages 30-65
  • No prevalent diagnosis of type 2 diabetes mellitus, either at the time of abdominal fat imaging or at study entry.
  • Previous abdominal fat quantification by magnetic resonance imaging in the Dallas Heart Study or possible neck-to-knee MRI for VAT measurement may be performed.

You may not qualify if:

  • Pregnant or breastfeeding
  • Incarcerated
  • Chronic kidney or liver disease
  • History of frequent (\>2/year) urinary tract infections
  • Non-obese either at time of abdominal fat imaging or at present.
  • Greater than 10% change in body weight (kg) between time of abdominal fat imaging and present.
  • Has donated blood within last 6 weeks
  • Cannot give informed consent, understand the protocol, or tolerate any aspect of the protocol
  • If undergoing MRI, persons with metal implants contraindicated for 3Tesla MRI exams will be excluded. Severe claustrophobia will also be assessed prior to an MRI exam.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (6)

  • Neeland IJ, Ayers CR, Rohatgi AK, Turer AT, Berry JD, Das SR, Vega GL, Khera A, McGuire DK, Grundy SM, de Lemos JA. Associations of visceral and abdominal subcutaneous adipose tissue with markers of cardiac and metabolic risk in obese adults. Obesity (Silver Spring). 2013 Sep;21(9):E439-47. doi: 10.1002/oby.20135. Epub 2013 May 19.

    PMID: 23687099BACKGROUND

  • Neeland IJ, Turer AT, Ayers CR, Powell-Wiley TM, Vega GL, Farzaneh-Far R, Grundy SM, Khera A, McGuire DK, de Lemos JA. Dysfunctional adiposity and the risk of prediabetes and type 2 diabetes in obese adults. JAMA. 2012 Sep 19;308(11):1150-9. doi: 10.1001/2012.jama.11132.

    PMID: 22990274BACKGROUND

  • Nurjhan N, Kennedy F, Consoli A, Martin C, Miles J, Gerich J. Quantification of the glycolytic origin of plasma glycerol: implications for the use of the rate of appearance of plasma glycerol as an index of lipolysis in vivo. Metabolism. 1988 Apr;37(4):386-9. doi: 10.1016/0026-0495(88)90140-0.

    PMID: 3357420BACKGROUND

  • Baba H, Zhang XJ, Wolfe RR. Glycerol gluconeogenesis in fasting humans. Nutrition. 1995 Mar-Apr;11(2):149-53.

    PMID: 7647479BACKGROUND

  • Jin ES, Sherry AD, Malloy CR. Interaction between the pentose phosphate pathway and gluconeogenesis from glycerol in the liver. J Biol Chem. 2014 Nov 21;289(47):32593-603. doi: 10.1074/jbc.M114.577692. Epub 2014 Oct 6.

    PMID: 25288790BACKGROUND

  • Neeland IJ, de Albuquerque Rocha N, Hughes C, Ayers CR, Malloy CR, Jin ES. Effects of Empagliflozin Treatment on Glycerol-Derived Hepatic Gluconeogenesis in Adults with Obesity: A Randomized Clinical Trial. Obesity (Silver Spring). 2020 Jul;28(7):1254-1262. doi: 10.1002/oby.22854.

    PMID: 32568464DERIVED

MeSH Terms

Conditions

Obesity, AbdominalObesityDiabetes Mellitus

Interventions

GlycerolempagliflozinSugars

Condition Hierarchy (Ancestors)

OverweightOvernutritionNutrition DisordersNutritional and Metabolic DiseasesBody WeightSigns and SymptomsPathological Conditions, Signs and SymptomsGlucose Metabolism DisordersMetabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

Triose Sugar AlcoholsSugar AlcoholsAlcoholsOrganic ChemicalsCarbohydrates

Results Point of Contact

Title
Ian J. Neeland MD
Organization
University of Texas Southwestern Medical Center
ian.neeland@utsouthwestern.edu
214-645-1267

Study Officials

  • Ian Neeland, MD

    University of Texas Southwestern Medical Center

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
M.D.

Study Record Dates

First Submitted

July 5, 2016

First Posted

July 14, 2016

Study Start

March 1, 2016

Primary Completion

January 1, 2018

Study Completion

November 1, 2018

Last Updated

January 23, 2020

Results First Posted

May 2, 2019

Record last verified: 2020-01

Data Sharing

IPD Sharing
Will share

IPD sharing will be done upon reasonable request.

Shared Documents
STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
Access Criteria
Email the PI with request.

Locations

US(1)