Trial Outcomes & Findings for Endothelial Hyperpolarization in Humans (NCT NCT00166166)

Results Overview

Simultaneous forearm blood flow (FBF) measurements were obtained in both arms using a dual-channel venous occlusion strain gauge plethysmograph at rest and after administration of tetraethylammonium (TEA). Flow measurements were recorded for approximately 7 seconds, every 15 seconds up to eight times and a mean FBF value was computed. Percent change is the difference from baseline FBF and after TEA administration.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

174 participants

Primary outcome timeframe

Baseline, 5 minutes

Results posted on

2018-08-15

Participant Flow

Participant milestones

Participant milestones
Measure	Healthy Controls Healthy subjects had venous occlusion plethysmography after intra-arterial infusions of saline, L-NG-monomethyl Arginine (L-NMMA), Tetraethylammonium (TEA), fluconazole, bradykinin, sodium nitroprusside and acetylcholine	Risk Factors Non-hypertensive subjects with cardiovascular risk factors had venous occlusion plethysmography after intra-arterial infusions of saline, L-NG-monomethyl Arginine (L-NMMA), Tetraethylammonium (TEA), fluconazole, bradykinin, sodium nitroprusside and acetylcholine
Overall Study STARTED	103	71
Overall Study COMPLETED	103	71
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Endothelial Hyperpolarization in Humans

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Healthy Controls n=103 Participants Healthy subjects had venous occlusion plethysmography after intra-arterial infusions of saline, L-NG-monomethyl Arginine (L-NMMA), Tetraethylammonium (TEA), fluconazole, bradykinin, sodium nitroprusside and acetylcholine	Risk Factors n=71 Participants Non-hypertensive subjects with cardiovascular risk factors had venous occlusion plethysmography after intra-arterial infusions of saline, L-NG-monomethyl Arginine (L-NMMA), Tetraethylammonium (TEA), fluconazole, bradykinin, sodium nitroprusside and acetylcholine	Total n=174 Participants Total of all reporting groups
Age, Continuous	34 years STANDARD_DEVIATION 11 • n=5 Participants	46 years STANDARD_DEVIATION 12 • n=7 Participants	40 years STANDARD_DEVIATION 12 • n=5 Participants
Sex: Female, Male Female	49 Participants n=5 Participants	32 Participants n=7 Participants	81 Participants n=5 Participants
Sex: Female, Male Male	54 Participants n=5 Participants	39 Participants n=7 Participants	93 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 5 minutes

Population: Only 62 of the original 174 subjects were treated for this portion of the study.

Simultaneous forearm blood flow (FBF) measurements were obtained in both arms using a dual-channel venous occlusion strain gauge plethysmograph at rest and after administration of tetraethylammonium (TEA). Flow measurements were recorded for approximately 7 seconds, every 15 seconds up to eight times and a mean FBF value was computed. Percent change is the difference from baseline FBF and after TEA administration.

Outcome measures

Outcome measures
Measure	Healthy Controls n=37 Participants Healthy subjects had venous occlusion plethysmography after intra-arterial infusions of saline (baseline) and Tetraethylammonium (TEA).	Risk Factors n=25 Participants Non-hypertensive subjects with cardiovascular risk factors had venous occlusion plethysmography after intra-arterial infusions of saline (baseline) and Tetraethylammonium (TEA)
Percent Change in Forearm Blood Flow (FBF) After Tetraethylammonium (TEA) Administration	-18 percent change Standard Error 16	-24 percent change Standard Error 13

PRIMARY outcome

Timeframe: Baseline, 5 minutes

Population: Only 62 of the original 174 subjects were treated for this portion of the study.

Simultaneous forearm blood flow (FBF) measurements were obtained in both arms using a dual-channel venous occlusion strain gauge plethysmograph after administration of L-NG-monomethyl Arginine (L-NMMA). Flow measurements were recorded for approximately 7 seconds, every 15 seconds up to eight times and a mean FBF value was computed. Percent change is the difference in FBF from baseline and after L-NMMA administration.

Outcome measures

Outcome measures
Measure	Healthy Controls n=37 Participants Healthy subjects had venous occlusion plethysmography after intra-arterial infusions of saline (baseline) and Tetraethylammonium (TEA).	Risk Factors n=25 Participants Non-hypertensive subjects with cardiovascular risk factors had venous occlusion plethysmography after intra-arterial infusions of saline (baseline) and Tetraethylammonium (TEA)
Percent Change in Forearm Blood Flow (FBF) After Administration of L-NG-monomethyl Arginine (L-NMMA)	-29 percent change Standard Error 17	-23 percent change Standard Error 15

SECONDARY outcome

Timeframe: 5 minutes, 10 minutes

Population: Only 62 of the original 174 subjects were treated for this portion of the study.

Simultaneous forearm blood flow (FBF) measurements were obtained in both arms using a dual-channel venous occlusion strain gauge plethysmograph after administration of L-NG-monomethyl Arginine (L-NMMA) and Tetraethylammonium (TEA). Flow measurements were recorded for approximately 7 seconds, every 15 seconds up to eight times and a mean FBF value was computed. Percent change is the difference in FBF from after L-NMMA administration and after TEA administration.

Outcome measures

Outcome measures
Measure	Healthy Controls n=37 Participants Healthy subjects had venous occlusion plethysmography after intra-arterial infusions of saline (baseline) and Tetraethylammonium (TEA).	Risk Factors n=25 Participants Non-hypertensive subjects with cardiovascular risk factors had venous occlusion plethysmography after intra-arterial infusions of saline (baseline) and Tetraethylammonium (TEA)
Percent Change in Forearm Blood Flow (FBF) After Administration of L-NG-monomethyl Arginine (L-NMMA) and Tetraethylammonium (TEA)	-38 percent change Standard Error 17	-39 percent change Standard Error 17

SECONDARY outcome

Timeframe: Baseline, 5 minutes

Population: Only 33 of the original 174 subjects were treated for this portion of the study.

Simultaneous forearm blood flow (FBF) measurements were obtained in both arms using a dual-channel venous occlusion strain gauge plethysmograph at rest and after administration of fluconazole. Flow measurements were recorded for approximately 7 seconds, every 15 seconds up to eight times and a mean FBF value was computed. Percent change is the difference from baseline FBF and after fluconazole administration.

Outcome measures

Outcome measures
Measure	Healthy Controls n=26 Participants Healthy subjects had venous occlusion plethysmography after intra-arterial infusions of saline (baseline) and Tetraethylammonium (TEA).	Risk Factors n=7 Participants Non-hypertensive subjects with cardiovascular risk factors had venous occlusion plethysmography after intra-arterial infusions of saline (baseline) and Tetraethylammonium (TEA)
Percent Change in Forearm Blood Flow (FBF) After Fluconazole Administration	-13 percent change Standard Error 16	-17 percent change Standard Error 13

SECONDARY outcome

Timeframe: 5 minutes, 10 minutes

Population: Only 15 of the original 174 subjects were treated for this portion of the study.

Simultaneous forearm blood flow (FBF) measurements were obtained in both arms using a dual-channel venous occlusion strain gauge plethysmograph after L-NMMA administration and administration of fluconazole. Flow measurements were recorded for approximately 7 seconds, every 15 seconds up to eight times and a mean FBF value was computed. Percent change is the difference in FBF after L-NMMA administration and then fluconazole administration.

Outcome measures

Outcome measures
Measure	Healthy Controls n=8 Participants Healthy subjects had venous occlusion plethysmography after intra-arterial infusions of saline (baseline) and Tetraethylammonium (TEA).	Risk Factors n=7 Participants Non-hypertensive subjects with cardiovascular risk factors had venous occlusion plethysmography after intra-arterial infusions of saline (baseline) and Tetraethylammonium (TEA)
Percent Change in Forearm Blood Flow (FBF) After L-NG-monomethyl Arginine (L-NMMA) and Fluconazole Administration	-26 percent change Standard Error 22	-26 percent change Standard Error 22

SECONDARY outcome

Timeframe: 5 minutes, 10 minutes

Population: Only 19 of the original 174 subjects were treated for this portion of the study.

Simultaneous forearm blood flow (FBF) measurements were obtained in both arms using a dual-channel venous occlusion strain gauge plethysmograph after administration of fluconazole and Tetraethylammonium (TEA) administration. Flow measurements were recorded for approximately 7 seconds, every 15 seconds up to eight times and a mean FBF value was computed. Percent change is the difference from FBF after fluconazole administration and after Tetraethylammonium (TEA) administration.

Outcome measures

Outcome measures
Measure	Healthy Controls n=19 Participants Healthy subjects had venous occlusion plethysmography after intra-arterial infusions of saline (baseline) and Tetraethylammonium (TEA).	Risk Factors Non-hypertensive subjects with cardiovascular risk factors had venous occlusion plethysmography after intra-arterial infusions of saline (baseline) and Tetraethylammonium (TEA)
Percent Change in Forearm Blood Flow (FBF) After Fluconazole and Tetraethylammonium (TEA) Administration	-22 percent change Standard Error 23	—

SECONDARY outcome

Timeframe: 5 minutes

Population: Only 80 of the original 174 subjects were treated for this portion of the study.

Simultaneous forearm blood flow (FBF) measurements were obtained in both arms using a dual-channel venous occlusion strain gauge plethysmograph after administration of sodium nitroprusside. Flow measurements were recorded for approximately 7 seconds, every 15 seconds up to eight times and a mean FBF value was computed.

Outcome measures

Outcome measures
Measure	Healthy Controls n=42 Participants Healthy subjects had venous occlusion plethysmography after intra-arterial infusions of saline (baseline) and Tetraethylammonium (TEA).	Risk Factors n=38 Participants Non-hypertensive subjects with cardiovascular risk factors had venous occlusion plethysmography after intra-arterial infusions of saline (baseline) and Tetraethylammonium (TEA)
Forearm Blood Flow (FBF) After Sodium Nitroprusside Administration	10.4 mL min^-1 * 100 mL^-1 Standard Error 4	10.9 mL min^-1 * 100 mL^-1 Standard Error 5

SECONDARY outcome

Timeframe: Baseline, 30 minutes

Population: Only 33 of the original 174 subjects were treated for this portion of the study.

Individual net t-PA release at each time point were calculated by the following formula: net release = (Cv-CA) x {FBF x \[101-hematocrit/100\]}, where Cv and CA represent the concentration of t-PA in the brachial vein and artery, respectively. Change is the difference of t-PA at baseline and t-PA after bradykinin 400 ng/min

Outcome measures

Outcome measures
Measure	Healthy Controls n=33 Participants Healthy subjects had venous occlusion plethysmography after intra-arterial infusions of saline (baseline) and Tetraethylammonium (TEA).	Risk Factors Non-hypertensive subjects with cardiovascular risk factors had venous occlusion plethysmography after intra-arterial infusions of saline (baseline) and Tetraethylammonium (TEA)
Change in Tissue Plasminogen Activator (t-PA) Release	5.6 ng/mL Standard Error 0.8	—

SECONDARY outcome

Timeframe: 30 minutes, 60 minutes

Population: Only 18 of the original 174 subjects were treated for this portion of the study.

Individual net t-PA release at each time point were calculated by the following formula: net release = (Cv-CA) x {FBF x \[101-hematocrit/100\]}, where Cv and CA represent the concentration of t-PA in the brachial vein and artery, respectively. Change is the difference of t-PA after Tetraethylammonium (TEA) and t-PA after bradykinin 400 ng/min

Outcome measures

Outcome measures
Measure	Healthy Controls n=18 Participants Healthy subjects had venous occlusion plethysmography after intra-arterial infusions of saline (baseline) and Tetraethylammonium (TEA).	Risk Factors Non-hypertensive subjects with cardiovascular risk factors had venous occlusion plethysmography after intra-arterial infusions of saline (baseline) and Tetraethylammonium (TEA)
Change in Tissue Plasminogen Activator (t-PA) Release After Tetraethylammonium (TEA) and Bradykinin Administration	0.03 ng/mL Standard Error 0.7	—

SECONDARY outcome

Timeframe: 30 minutes, 60 minutes

Population: Only 11 of the original 174 subjects were treated for this portion of the study.

Individual net t-PA release at each time point were calculated by the following formula: net release = (Cv-CA) x {FBF x \[101-hematocrit/100\]}, where Cv and CA represent the concentration of t-PA in the brachial vein and artery, respectively. Change is the difference of t-PA after fluconazole and t-PA after bradykinin 400 ng/min

Outcome measures

Outcome measures
Measure	Healthy Controls n=11 Participants Healthy subjects had venous occlusion plethysmography after intra-arterial infusions of saline (baseline) and Tetraethylammonium (TEA).	Risk Factors Non-hypertensive subjects with cardiovascular risk factors had venous occlusion plethysmography after intra-arterial infusions of saline (baseline) and Tetraethylammonium (TEA)
Change in Tissue Plasminogen Activator (t-PA) Release After Fluconazole and Bradykinin Administration	4.4 ng/mL Standard Error 1.4	—

SECONDARY outcome

Timeframe: 60 minutes, 90 minutes

Population: Only 10 of the original 174 subjects were treated for this portion of the study.

Individual net t-PA release at each time point were calculated by the following formula: net release = (Cv-CA) x {FBF x \[101-hematocrit/100\]}, where Cv and CA represent the concentration of t-PA in the brachial vein and artery, respectively. Change is the difference of t-PA after fluconazole and tetraethylammonium (TEA) and t-PA after bradykinin 400 ng/min

Outcome measures

Outcome measures
Measure	Healthy Controls n=10 Participants Healthy subjects had venous occlusion plethysmography after intra-arterial infusions of saline (baseline) and Tetraethylammonium (TEA).	Risk Factors Non-hypertensive subjects with cardiovascular risk factors had venous occlusion plethysmography after intra-arterial infusions of saline (baseline) and Tetraethylammonium (TEA)
Change in Tissue Plasminogen Activator (t-PA) Release After Fluconazole, Tetraethylammonium (TEA), and Bradykinin Administration	1.6 ng/mL Standard Error 0.4	—

Adverse Events

Healthy Controls

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Risk Factors

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. Arshed Quyyumi

Emory University

Phone: 404-727-3655

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place