Trial Outcomes & Findings for PROTOCOL 3: Role of the Renal Nerves in the Increase in EGP in Response to Glucosuria (NCT NCT03168295)

Results Overview

Renal transplant subjects with native kidneys intact underwent measurement of EGP with an 8 hour infusion of 3-3H-glucose on 2 separate days with the administration in random order of either dapagliflozin 10mg or placebo after 3 hours of the tracer equilibration period. The equilibration at 3 hours was considered the baseline measurement. Measurement of change in endogenous glucose production was obtained for all subjects.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

34 participants

Primary outcome timeframe

baseline and 240-300 minutes

Results posted on

2020-09-17

Participant Flow

Diabetic and non-diabetic subjects were assigned to both interventions after randomization, either dapagliflozin first with placebo second, or placebo first and then dapagliflozin next.

Participant milestones

Participant milestones
Measure	Dapagliflozin First - Diabetic Subjects who have undergone renal transplant are randomly assigned to receive either dapagliflozin first followed by the placebo	Placebo Oral Tablet First - Diabetic Subjects who have undergone renal transplant are randomly assigned to receive placebo first followed by dapagliflozin	Dapagliflozin First - Non-diabetic Non-diabetic subjects who have undergone renal transplant are randomly assigned to dapagliflozin first and then receive placebo	Placebo Oral Tablet First - Non-diabetic Non-diabetic subjects who have undergone renal transplant are randomly assigned to placebo first and then receive dapagliflozin	Control Group Type 2 Diabetic subjects who did not undergo renal transplant and received dapagliflozin
Overall Study STARTED	3	3	4	4	20
Overall Study COMPLETED	3	3	4	4	20
Overall Study NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

6 of the subjects analyzed were diabetic and the remaining 8 were non-diabetic

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Diabetic Subjects n=6 Participants Diabetic renal transplant subjects with native kidneys intact who were Type 2 diabetics	Non-diabetic Subjects n=8 Participants Non-diabetic subjects after renal transplant with intact native kidneys	Control Group n=20 Participants Type 2 diabetic subjects who did not under go renal transplant	Total n=34 Participants Total of all reporting groups
Age, Customized Subjects between 18 and 70 years	6 Participants n=5 Participants	8 Participants n=7 Participants	20 Participants n=5 Participants	34 Participants n=4 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants	17 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants	17 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic	5 Participants n=5 Participants • 6 of the subjects analyzed were diabetic and the remaining 8 were non-diabetic	5 Participants n=7 Participants • 6 of the subjects analyzed were diabetic and the remaining 8 were non-diabetic	12 Participants n=5 Participants • 6 of the subjects analyzed were diabetic and the remaining 8 were non-diabetic	22 Participants n=4 Participants • 6 of the subjects analyzed were diabetic and the remaining 8 were non-diabetic
Race/Ethnicity, Customized White Non-Hispanic	1 Participants n=5 Participants • 6 of the subjects analyzed were diabetic and the remaining 8 were non-diabetic	1 Participants n=7 Participants • 6 of the subjects analyzed were diabetic and the remaining 8 were non-diabetic	8 Participants n=5 Participants • 6 of the subjects analyzed were diabetic and the remaining 8 were non-diabetic	10 Participants n=4 Participants • 6 of the subjects analyzed were diabetic and the remaining 8 were non-diabetic
Race/Ethnicity, Customized Black Non-Hispanic	0 Participants n=5 Participants • 6 of the subjects analyzed were diabetic and the remaining 8 were non-diabetic	2 Participants n=7 Participants • 6 of the subjects analyzed were diabetic and the remaining 8 were non-diabetic	0 Participants n=5 Participants • 6 of the subjects analyzed were diabetic and the remaining 8 were non-diabetic	2 Participants n=4 Participants • 6 of the subjects analyzed were diabetic and the remaining 8 were non-diabetic
Region of Enrollment United States	6 participants n=5 Participants	8 participants n=7 Participants	20 participants n=5 Participants	34 participants n=4 Participants
A1C (average blood glucose level over 3 months)	7.2 Percentage of glycated hemoglobin STANDARD_DEVIATION 0.1 • n=5 Participants	5.6 Percentage of glycated hemoglobin STANDARD_DEVIATION 0.1 • n=7 Participants	7.5 Percentage of glycated hemoglobin STANDARD_DEVIATION 0.2 • n=5 Participants	6.4 Percentage of glycated hemoglobin STANDARD_DEVIATION 0.1 • n=4 Participants

PRIMARY outcome

Timeframe: baseline and 240-300 minutes

Population: The control group did not have renal surgery and were only administered the dapagliflozin, not the placebo, so no participants show for baseline or 240 to 300 minutes for placebo measurements, only for dapagliflozin.

Renal transplant subjects with native kidneys intact underwent measurement of EGP with an 8 hour infusion of 3-3H-glucose on 2 separate days with the administration in random order of either dapagliflozin 10mg or placebo after 3 hours of the tracer equilibration period. The equilibration at 3 hours was considered the baseline measurement. Measurement of change in endogenous glucose production was obtained for all subjects.

Outcome measures

Outcome measures
Measure	Diabetic Subjects n=6 Participants Renal transplant subjects with native kidneys intact who were Type 2 diabetics	Non-diabetic Subjects n=8 Participants Non-diabetic subjects after renal transplant with intact native kidneys	Control Group n=20 Participants Type 2 diabetic subjects who did not undergo renal surgery and received dapagliflozin
Change in Endogenous Glucose Production (EGP) Baseline Measurement Placebo	2.03 mg/kg.min Standard Deviation 0.20	1.92 mg/kg.min Standard Deviation 0.10	—
Change in Endogenous Glucose Production (EGP) 240-300 minute measurement Placebo	1.55 mg/kg.min Standard Deviation 0.09	1.68 mg/kg.min Standard Deviation 0.10	—
Change in Endogenous Glucose Production (EGP) Baseline Measurement Dapagliflozin	2.21 mg/kg.min Standard Deviation 0.19	1.85 mg/kg.min Standard Deviation 0.10	2.5 mg/kg.min Standard Deviation 0.1
Change in Endogenous Glucose Production (EGP) 240-300 minute measurement Dapagliflozin	1.96 mg/kg.min Standard Deviation 0.14	1.78 mg/kg.min Standard Deviation 0.10	2.6 mg/kg.min Standard Deviation 0.1

SECONDARY outcome

Timeframe: baseline and 240-300 minutes

Population: Only type 2 diabetic subjects were included in this group, so the 8 non-diabetic renal transplant subjects were not included.

Change in Fasting Plasma Glucose in Type 2 Diabetes Mellitus subjects only

Outcome measures

Outcome measures
Measure	Diabetic Subjects n=6 Participants Renal transplant subjects with native kidneys intact who were Type 2 diabetics	Non-diabetic Subjects n=20 Participants Non-diabetic subjects after renal transplant with intact native kidneys	Control Group Type 2 diabetic subjects who did not undergo renal surgery and received dapagliflozin
Change in Fasting Plasma Glucose Baseline Measurement Placebo	143 mg/dL Standard Deviation 14	—	—
Change in Fasting Plasma Glucose 240-300 minute measurement Placebo	124 mg/dL Standard Deviation 10	—	—
Change in Fasting Plasma Glucose Baseline Measurement Dapagliflozin	143 mg/dL Standard Deviation 15	135.7 mg/dL Standard Deviation 2.6	—
Change in Fasting Plasma Glucose 240-300 minute measurement Dapagliflozin	112 mg/dL Standard Deviation 9	106.6 mg/dL Standard Deviation 1.3	—

SECONDARY outcome

Timeframe: baseline and 240-300 minutes

Population: Only type 2 diabetic subjects were included in this group, so the 8 subjects who were non-diabetic who had renal transplant were not included.

Change in Fasting Plasma Insulin in Type 2 Diabetes Mellitus subjects in diabetic subjects only