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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03852901
Recruitment Status : Completed
First Posted : February 25, 2019
Results First Posted : August 2, 2022
Last Update Posted : August 2, 2022
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute on Aging (NIA) )

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Basic Science
Conditions Empaglifozin
Physiological Effects of Drugs
Hypoglycemic Agents
Sodium-Glucose Transporter 2 Inhibitors
Intervention Drug: empagliflozin (Jardiance) 25 mg
Enrollment 21
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Single Arm
Hide Arm/Group Description The single group of the study (empagliflozin group) took empagliflozin 25mg/day for 14 days.
Period Title: Overall Study
Started 21
Completed 20
Not Completed 1
Arm/Group Title Single Arm
Hide Arm/Group Description The single group underwent baseline assessment (visit 1). Fourteen days later (visit 2), participants took the first empagliflozin dose and acute effects were assessed. Participants continued taking empagliflozin once per day at home for 13 additional days, and returned for the final visit (visit 3) in which chronic effects were assessed.
Overall Number of Baseline Participants 21
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 21 participants
62.14  (6.91)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants
Female
11
  52.4%
Male
10
  47.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
3
  14.3%
White
18
  85.7%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 21 participants
21
1.Primary Outcome
Title Change in Serum β-hydroxybutyrate (BHB)
Hide Description Change in serum β-hydroxybutyrate (BHB) after 14 days on empagliflozin, compared with baseline.
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Single Arm
Hide Arm/Group Description:
The single group underwent baseline assessment (visit 1). Fourteen days later (visit 2), participants took the first empagliflozin dose and acute effects were assessed. Participants continued taking empagliflozin once per day at home for 13 additional days, and returned for the final visit (visit 3) in which chronic effects were assessed.
Overall Number of Participants Analyzed 21
Mean (Standard Error)
Unit of Measure: µM
40.717  (4.866)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Single Arm
Comments No a-priori power calculation was performed due to the exploratory nature of the study.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Type III of fixed effects. Num df = 1; Den df = 902.758; F = 70.003; Sig. < 0.001 (threshold for statistical significance p < 0.05)
Method Mixed Models Analysis
Comments Random effect: ID; Repeated measures: Visit & Timepoint; Fixed effects: Visit, Timepoint, Sex, Visit*Sex
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 40.717
Confidence Interval (2-Sided) 95%
31.166 to 50.268
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.866
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change in Plasma Glucose
Hide Description Change in plasma glucose after 14 days on empagliflozin, compared with baseline.
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Single Arm
Hide Arm/Group Description:
The single group underwent baseline assessment (visit 1). Fourteen days later (visit 2), participants took the first empagliflozin dose and acute effects were assessed. Participants continued taking empagliflozin once per day at home for 13 additional days, and returned for the final visit (visit 3) in which chronic effects were assessed.
Overall Number of Participants Analyzed 21
Mean (Standard Error)
Unit of Measure: mg/dl
-.637  (1.051)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Single Arm
Comments No a-priori power calculation was performed due to the exploratory nature of the study.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.545
Comments Type III of fixed effects. Num df = 1; Den df = 884.229; F = .367; Sig = .545 (threshold for statistical significance p < 0.05)
Method Mixed Models Analysis
Comments Random effect: ID; Repeated measures: Visit & Timepoint; Fixed effects: Visit, Timepoint, Sex, Visit*Sex
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.637
Confidence Interval (2-Sided) 95%
-2.699 to 1.426
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.051
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change in Serum Non-esterified Fatty Acids (NEFAs)
Hide Description Change in serum non-esterified fatty acids (NEFAs) after 14 days on empagliflozin, compared with baseline.
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Single Arm
Hide Arm/Group Description:
The single group underwent baseline assessment (visit 1). Fourteen days later (visit 2), participants took the first empagliflozin dose and acute effects were assessed. Participants continued taking empagliflozin once per day at home for 13 additional days, and returned for the final visit (visit 3) in which chronic effects were assessed.
Overall Number of Participants Analyzed 21
Mean (Standard Error)
Unit of Measure: mEq/L
.027  (.009)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Single Arm
Comments No a-priori power calculation was performed due to the exploratory nature of the study.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments Type III of fixed effects. Num df = 1; Den df = 880.629; F = 8.782; Sig. = 0.003 (threshold for statistical significance p < 0.05)
Method Mixed Models Analysis
Comments Random effect: ID; Repeated measures: Visit & Timepoint; Fixed effects: Visit, Timepoint, Sex, Visit*Sex
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.027
Confidence Interval (2-Sided) 95%
.009 to .044
Parameter Dispersion
Type: Standard Error of the Mean
Value: .009
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change in Plasma Insulin
Hide Description Change in plasma insulin after 14 days on empagliflozin, compared with baseline.
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Single Arm
Hide Arm/Group Description:
The single group underwent baseline assessment (visit 1). Fourteen days later (visit 2), participants took the first empagliflozin dose and acute effects were assessed. Participants continued taking empagliflozin once per day at home for 13 additional days, and returned for the final visit (visit 3) in which chronic effects were assessed.
Overall Number of Participants Analyzed 21
Mean (Standard Error)
Unit of Measure: mIU/L
-2.647  (1.329)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Single Arm
Comments No a-priori power calculation was performed due to the exploratory nature of the study.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.047
Comments Type III of fixed effects. Num df = 1; Den df = 880.870; F = 3.970; Sig. = 0.047 (threshold for statistical significance p < 0.05)
Method Mixed Models Analysis
Comments Random effect: ID; Repeated measures: Visit & Timepoint; Fixed effects: Visit, Timepoint, Sex, Visit*Sex
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.647
Confidence Interval (2-Sided) 95%
-5.255 to -0.040
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.329
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change in Serum Acetoacetate (AcAc)
Hide Description Change in serum Acetoacetate (AcAc) after 14 days on empagliflozin, compared with baseline.
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Single Arm
Hide Arm/Group Description:
The single group underwent baseline assessment (visit 1). Fourteen days later (visit 2), participants took the first empagliflozin dose and acute effects were assessed. Participants continued taking empagliflozin once per day at home for 13 additional days, and returned for the final visit (visit 3) in which chronic effects were assessed.
Overall Number of Participants Analyzed 21
Mean (Standard Error)
Unit of Measure: µM
-5.573  (1.853)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Single Arm
Comments No a-priori power calculation was performed due to the exploratory nature of the study.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments Type III of fixed effects. Num df = 1; Den df = 902.181; F = 9.049; Sig. = 0.003 (threshold for statistical significance p < 0.05)
Method Mixed Models Analysis
Comments Random effect: ID; Repeated measures: Visit & Timepoint; Fixed effects: repeated-measures. Visit, Timepoint, Sex, Visit*Sex
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.573
Confidence Interval (2-Sided) 95%
-9.210 to -1.937
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.853
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change in 1H MRS BHB
Hide Description Change in 1H MRS β-hydroxybutyrate (BHB) after 14 days on empagliflozin, compared with baseline.
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Single Arm
Hide Arm/Group Description:
The single group underwent baseline assessment (visit 1). Fourteen days later (visit 2), participants took the first empagliflozin dose and acute effects were assessed. Participants continued taking empagliflozin once per day at home for 13 additional days, and returned for the final visit (visit 3) in which chronic effects were assessed.
Overall Number of Participants Analyzed 20
Mean (Standard Error)
Unit of Measure: mmol/L
0.04  (0.03)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Single Arm
Comments No a-priori power calculation was performed due to the exploratory nature of the study.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5849
Comments Type III of fixed effects. Num df: 2; Den df = 33; F = 0.5451; Sig. = 0.5849 (threshold for statistical significance p < 0.05)
Method Mixed Models Analysis
Comments Random effect: ID; Repeated measures: Visit; Fixed effects: Visit, Sex, Age, fCSF
7.Secondary Outcome
Title Change in 1H MRS Glutamate (Glu)
Hide Description Change in 1H MRS glutamate (Glu) after 14 days on empagliflozin, compared with baseline.
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Single Arm
Hide Arm/Group Description:
The single group underwent baseline assessment (visit 1). Fourteen days later (visit 2), participants took the first empagliflozin dose and acute effects were assessed. Participants continued taking empagliflozin once per day at home for 13 additional days, and returned for the final visit (visit 3) in which chronic effects were assessed.
Overall Number of Participants Analyzed 20
Mean (Standard Error)
Unit of Measure: mmol/L
-0.23  (0.11)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Single Arm
Comments No a-priori power calculation was performed due to the exploratory nature of the study.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0142
Comments Type III of fixed effects. Num df = 2; Den df = 35; F = 4.8191; Sig. = 0.0142 (threshold for statistical significance p < 0.05)
Method Mixed Models Analysis
Comments Random effect: ID; Repeated measures: Visit; Fixed effects: Visit, Sex, Age, fCSF
8.Secondary Outcome
Title Change in 1H MRS Glutamine (Gln)
Hide Description Change in 1H MRS glutamine (Gln) after 14 days on empagliflozin, compared with baseline.
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Single Arm
Hide Arm/Group Description:
The single group underwent baseline assessment (visit 1). Fourteen days later (visit 2), participants took the first empagliflozin dose and acute effects were assessed. Participants continued taking empagliflozin once per day at home for 13 additional days, and returned for the final visit (visit 3) in which chronic effects were assessed.
Overall Number of Participants Analyzed 20
Mean (Standard Error)
Unit of Measure: mmol/L
-0.27  (0.12)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Single Arm
Comments No a-priori power calculation was performed due to the exploratory nature of the study.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.024
Comments Type III of fixed effects. Num df: 2; Den df = 34; F = 4.1501; Sig. = 0.0244 (threshold for statistical significance p < 0.05)
Method Mixed Models Analysis
Comments Random effects: ID; Repeated measures: Visit; Fixed effects: Visit, Sex, Age and fCSF
Time Frame 14 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Single Arm
Hide Arm/Group Description The single group underwent baseline assessment (visit 1). Fourteen days later (visit 2), participants took the first empagliflozin dose and acute effects were assessed. Participants continued taking empagliflozin once per day at home for 13 additional days, and returned for the final visit (visit 3) in which chronic effects were assessed.
All-Cause Mortality
Single Arm
Affected / at Risk (%)
Total   0/21 (0.00%)    
Hide Serious Adverse Events
Single Arm
Affected / at Risk (%) # Events
Total   0/21 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Single Arm
Affected / at Risk (%) # Events
Total   1/21 (4.76%)    
Renal and urinary disorders   
Mild creatinine elevation * [1]  1/21 (4.76%)  1
*
Indicates events were collected by non-systematic assessment
[1]
Mild creatinine elevation.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Josephine M. Egan, MD, Clinical Director
Organization: National Institute on Aging
Phone: 410-558-8414
EMail: eganj@mail.nih.gov
Layout table for additonal information
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute on Aging (NIA) )
ClinicalTrials.gov Identifier: NCT03852901    
Other Study ID Numbers: 190060
19-AG-0060
First Submitted: February 22, 2019
First Posted: February 25, 2019
Results First Submitted: April 11, 2022
Results First Posted: August 2, 2022
Last Update Posted: August 2, 2022