Trial Outcomes & Findings for An Investigation Into The Anti-hypertensive And Potential Anti-inflammatory Actions Of Dapagliflozin (NCT NCT02433678)

NCT ID: NCT02433678

Last Updated: 2019-10-30

Results Overview

nuclear factor kappa-light-chain-enhancer of activated B cells measurement through Transcription factor assay

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 52 participants
• Primary outcome timeframe: 12 weeks
• Results posted on: 2019-10-30

Participant Flow

Participant milestones

Measure	Placebo Patients will be treated for 12 weeks with placebo once daily Placebo	Dapagliflozin 10 mg daily for the 12 weeks dapagliflozin: SGLT-2 inhibitor for the treatment of type 2 diabetes
Overall Study STARTED	26	26
Overall Study COMPLETED	25	24
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Measure	Placebo Patients will be treated for 12 weeks with placebo once daily Placebo	Dapagliflozin 10 mg daily for the 12 weeks dapagliflozin: SGLT-2 inhibitor for the treatment of type 2 diabetes
Overall Study Lost to Follow-up	1	2

Baseline Characteristics

An Investigation Into The Anti-hypertensive And Potential Anti-inflammatory Actions Of Dapagliflozin

Baseline characteristics by cohort

Measure	Placebo n=26 Participants Patients will be treated for 12 weeks with placebo once daily Placebo	Dapagliflozin n=26 Participants 10 mg daily for the 12 weeks dapagliflozin: SGLT-2 inhibitor for the treatment of type 2 diabetes	Total n=52 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=5 Participants	22 Participants n=7 Participants	38 Participants n=5 Participants
Age, Categorical >=65 years	10 Participants n=5 Participants	4 Participants n=7 Participants	14 Participants n=5 Participants
Age, Continuous	61 years STANDARD_DEVIATION 10 • n=5 Participants	61 years STANDARD_DEVIATION 9 • n=7 Participants	61 years STANDARD_DEVIATION 9 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	11 Participants n=7 Participants	19 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	15 Participants n=7 Participants	33 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) White	18 Participants n=5 Participants	17 Participants n=7 Participants	35 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	26 participants n=5 Participants	26 participants n=7 Participants	52 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: Out of the 26 total patients in each group, 4 dropped in the placebo arm and 3 dropped in the Dapagliflozin arm

nuclear factor kappa-light-chain-enhancer of activated B cells measurement through Transcription factor assay

Outcome measures

Measure	Placebo n=22 Participants Patients will be treated for 12 weeks with placebo once daily Placebo	Dapagliflozin n=23 Participants 10 mg daily for the 12 weeks dapagliflozin: SGLT-2 inhibitor for the treatment of type 2 diabetes
Difference in the Percent Change in Fasting Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells Activation (DNA Binding Activity) in Mononuclear Cells Before and After Dapagliflozin Use 12 week	0.776 arbitrary unit Standard Deviation 0.15	0.815 arbitrary unit Standard Deviation 0.12
Difference in the Percent Change in Fasting Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells Activation (DNA Binding Activity) in Mononuclear Cells Before and After Dapagliflozin Use baseline	0.762 arbitrary unit Standard Deviation 0.14	0.733 arbitrary unit Standard Deviation 0.11
Difference in the Percent Change in Fasting Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells Activation (DNA Binding Activity) in Mononuclear Cells Before and After Dapagliflozin Use 6 week	0.802 arbitrary unit Standard Deviation 0.12	0.835 arbitrary unit Standard Deviation 0.13

SECONDARY outcome

Timeframe: 12 Weeks

Population: Out of the 26 total patients in each group, 4 dropped in the placebo arm and 3 dropped in the Dapagliflozin arm

p47phox in mononuclear cells through real time polymerase chain reaction

Outcome measures

Measure	Placebo n=22 Participants Patients will be treated for 12 weeks with placebo once daily Placebo	Dapagliflozin n=23 Participants 10 mg daily for the 12 weeks dapagliflozin: SGLT-2 inhibitor for the treatment of type 2 diabetes
Changes in Expression of Inflammatory Mediators baseline	100 arbitrary unit Standard Deviation 0	100 arbitrary unit Standard Deviation 0
Changes in Expression of Inflammatory Mediators 12 week	92 arbitrary unit Standard Deviation 14	104 arbitrary unit Standard Deviation 12

SECONDARY outcome

Timeframe: 12 weeks

Population: Out of the 26 patients in each group, 4 dropped in the placebo arm and 3 dropped in the drug arm

Suppressor Of Cytokine Signaling 3 measurement in Mononuclear cells through real time polymerase chain reaction

Outcome measures

Measure	Placebo n=22 Participants Patients will be treated for 12 weeks with placebo once daily Placebo	Dapagliflozin n=23 Participants 10 mg daily for the 12 weeks dapagliflozin: SGLT-2 inhibitor for the treatment of type 2 diabetes
Changes in Expression of Inflammatory Mediators baseline	0.72 arbitrary unit Standard Deviation 0.20	0.60 arbitrary unit Standard Deviation 0.17
Changes in Expression of Inflammatory Mediators 12 week	0.70 arbitrary unit Standard Deviation 0.19	0.66 arbitrary unit Standard Deviation 0.19

SECONDARY outcome

Timeframe: 12 weeks

Population: Out of the 26 patients in each group, 4 dropped in the placebo arm and 3 dropped in the drug arm

Interleukin 1 Beta measurement in mononuclear cells through real time polymerase chain reaction

Outcome measures

Measure	Placebo n=22 Participants Patients will be treated for 12 weeks with placebo once daily Placebo	Dapagliflozin n=23 Participants 10 mg daily for the 12 weeks dapagliflozin: SGLT-2 inhibitor for the treatment of type 2 diabetes
Changes in Expression of Inflammatory Mediators baseline	0.697 arbitrary unit Standard Deviation 0.21	0.756 arbitrary unit Standard Deviation 0.19
Changes in Expression of Inflammatory Mediators 12 week	0.705 arbitrary unit Standard Deviation 0.21	0.741 arbitrary unit Standard Deviation 0.17

SECONDARY outcome

Timeframe: 12 weeks

Population: Out of the 26 patients in each group, 4 dropped in the placebo arm and 3 dropped in the drug arm

c-Jun N-terminal kinase 1 measurement in Mononuclear cells through real time polymerase chain reaction

Outcome measures

Measure	Placebo n=22 Participants Patients will be treated for 12 weeks with placebo once daily Placebo	Dapagliflozin n=23 Participants 10 mg daily for the 12 weeks dapagliflozin: SGLT-2 inhibitor for the treatment of type 2 diabetes
Changes in Expression of Inflammatory Mediators baseline	0.802 arbitrary unit Standard Deviation 0.19	0.856 arbitrary unit Standard Deviation 0.20
Changes in Expression of Inflammatory Mediators 12 week	0.810 arbitrary unit Standard Deviation 0.21	0.820 arbitrary unit Standard Deviation 0.19

SECONDARY outcome

Timeframe: 12 weeks

Population: Out of the 26 patients in each group, 4 dropped in the placebo arm and 3 dropped in the drug arm

Toll-like receptor 4 measurement in mononuclear cells through real time polymerase chain reaction

Outcome measures

Measure	Placebo n=22 Participants Patients will be treated for 12 weeks with placebo once daily Placebo	Dapagliflozin n=23 Participants 10 mg daily for the 12 weeks dapagliflozin: SGLT-2 inhibitor for the treatment of type 2 diabetes
Changes in Expression of Inflammatory Mediators baseline	0.704 arbitrary unit Standard Deviation 0.15	0.774 arbitrary unit Standard Deviation 0.21
Changes in Expression of Inflammatory Mediators 12 week	0.708 arbitrary unit Standard Deviation 0.17	0.731 arbitrary unit Standard Deviation 0.13

SECONDARY outcome

Timeframe: 12 weeks

Population: Out of the 26 patients in each group, 4 dropped in the placebo arm and 3 dropped in the drug arm

Tumor necrosis factor alpha measurement in mononuclear through real time polymerase chain reaction

Outcome measures

Measure	Placebo n=22 Participants Patients will be treated for 12 weeks with placebo once daily Placebo	Dapagliflozin n=23 Participants 10 mg daily for the 12 weeks dapagliflozin: SGLT-2 inhibitor for the treatment of type 2 diabetes
Changes in Expression of Inflammatory Mediators baseline	0.762 arbitrary unit Standard Deviation 0.14	0.733 arbitrary unit Standard Deviation 0.11
Changes in Expression of Inflammatory Mediators 12 week	0.776 arbitrary unit Standard Deviation 0.15	0.815 arbitrary unit Standard Deviation 0.12

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

Population: Out of the 26 patients in each group, 4 dropped in the placebo arm and 3 dropped in the drug arm

Plasma concentrations measurement of Angiotensinogen through enzyme-linked immunosorbent assay

Outcome measures

Measure	Placebo n=22 Participants Patients will be treated for 12 weeks with placebo once daily Placebo	Dapagliflozin n=23 Participants 10 mg daily for the 12 weeks dapagliflozin: SGLT-2 inhibitor for the treatment of type 2 diabetes
Change in Hypertension Mediators baseline	7.08 ug/mL Standard Deviation 0.41	7.23 ug/mL Standard Deviation 0.60
Change in Hypertension Mediators 12 week	6.98 ug/mL Standard Deviation 0.38	5.88 ug/mL Standard Deviation 0.64

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

Population: Out of the 26 patients in each group, 4 dropped in the placebo arm and 3 dropped in the drug arm

Plasma concentration measurement of Angitosensin II through enzyme-linked immunosorbent assay

Outcome measures

Measure	Placebo n=22 Participants Patients will be treated for 12 weeks with placebo once daily Placebo	Dapagliflozin n=23 Participants 10 mg daily for the 12 weeks dapagliflozin: SGLT-2 inhibitor for the treatment of type 2 diabetes
Change in Hypertension Mediators baseline	24.5 pg/mL Standard Deviation 5.5	29.2 pg/mL Standard Deviation 6.5
Change in Hypertension Mediators 12 week	25.1 pg/mL Standard Deviation 5.9	19.6 pg/mL Standard Deviation 7.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

Population: Out of the 26 patients in each group, 4 dropped in the placebo arm and 3 dropped in the drug arm

Plasma concentration measurement of Renin through enzyme-linked immunosorbent assay

Outcome measures

Measure	Placebo n=22 Participants Patients will be treated for 12 weeks with placebo once daily Placebo	Dapagliflozin n=23 Participants 10 mg daily for the 12 weeks dapagliflozin: SGLT-2 inhibitor for the treatment of type 2 diabetes
Change in Hypertension Mediators baseline	1599 pg/mL Standard Deviation 492	1630 pg/mL Standard Deviation 133
Change in Hypertension Mediators 12 week	1632 pg/mL Standard Deviation 543	1844 pg/mL Standard Deviation 145

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

Population: Out of the 26 patients in each group, 4 dropped in the placebo arm and 3 dropped in the drug arm

Plasma concentration measurement of Atrial natriuretic peptide through enzyme linked immunosorbent assay

Outcome measures

Measure	Placebo n=22 Participants Patients will be treated for 12 weeks with placebo once daily Placebo	Dapagliflozin n=23 Participants 10 mg daily for the 12 weeks dapagliflozin: SGLT-2 inhibitor for the treatment of type 2 diabetes
Change in Hypertension Mediators baseline	83 pg/mL Standard Deviation 12	92 pg/mL Standard Deviation 8
Change in Hypertension Mediators 12 week	86 pg/mL Standard Deviation 18	125 pg/mL Standard Deviation 37

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

Population: Out of the 26 patients in each group, 4 dropped in the placebo arm and 3 dropped in the drug arm

Plasma concentration measurement of B-type natriuretic peptide through enzyme linked immunosorbent assay

Outcome measures

Measure	Placebo n=22 Participants Patients will be treated for 12 weeks with placebo once daily Placebo	Dapagliflozin n=23 Participants 10 mg daily for the 12 weeks dapagliflozin: SGLT-2 inhibitor for the treatment of type 2 diabetes
Change in Hypertension Mediators baseline	59.2 pg/mL Standard Deviation 12.9	64.7 pg/mL Standard Deviation 13.7
Change in Hypertension Mediators 12 week	64.3 pg/mL Standard Deviation 20.1	62.9 pg/mL Standard Deviation 13.8

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

Population: Out of the 26 patients in each group, 4 dropped in the placebo arm and 3 dropped in the drug arm

Plasma concentration measurement of Cyclic guanosine monophosphate through enzyme linked immunosorbent assay

Outcome measures

Measure	Placebo n=22 Participants Patients will be treated for 12 weeks with placebo once daily Placebo	Dapagliflozin n=23 Participants 10 mg daily for the 12 weeks dapagliflozin: SGLT-2 inhibitor for the treatment of type 2 diabetes
Change in Hypertension Mediators baseline	64 pmol/mL Standard Deviation 18	73 pmol/mL Standard Deviation 11
Change in Hypertension Mediators 12 week	73 pmol/mL Standard Deviation 22	89 pmol/mL Standard Deviation 12

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 week

Population: Out of the 26 patients in each group, 4 dropped in the placebo arm and 3 dropped in the drug arm

Plasma concentration measurment of Cyclic adenosine monophosphate through enzyme linked immunosorbent assay

Outcome measures

Measure	Placebo n=22 Participants Patients will be treated for 12 weeks with placebo once daily Placebo	Dapagliflozin n=23 Participants 10 mg daily for the 12 weeks dapagliflozin: SGLT-2 inhibitor for the treatment of type 2 diabetes
Change in Hypertension Mediators baseline	80 pmol/mL Standard Deviation 4	78 pmol/mL Standard Deviation 5
Change in Hypertension Mediators 12 week	77 pmol/mL Standard Deviation 5	80 pmol/mL Standard Deviation 5

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Dapagliflozin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Paresh Dandona

University at Buffalo

Phone: 716-535-1850

Email: dandona@buffalo.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place