Trial Outcomes & Findings for Ischemia/Reperfusion Injury of Human Endothelium: Role of Glucose and Statins (NCT NCT00995670)
NCT ID: NCT00995670
Last Updated: 2015-03-17
Results Overview
endothelial (forearm blood flow) responses to acetylcholine stimulation at baseline, and under conditions of high glucose before and after ischemia/reperfusion injury, and same with the addition of an intervention: sevoflurane (Arm 1), vitamin C (Arm 2), and high statin (Arm 3).
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
59 participants
Primary outcome timeframe
Baseline, Glucose Control, 15-min post ischemia
Results posted on
2015-03-17
Participant Flow
Volunteers were sought from our research subject database.
None. This was not a clinical intervention study but basic science research in young healthy humans. Primary exclusion criteria included anyone on beta-blockers or other med that would affect vascular responses; pregnant or lactating women; substance abusers; smokers; and cardiovascular, renal or systemic disease including hypertension \& diabetes.
Participant milestones
| Measure |
Sevoflurane and Glucose
Endothelial function will be measured via forearm blood flow (FBF). Subjects may get I/R injury (ischemia) without glucose or sevoflurane (placebo trial); I/R with glucose only (glucose trial); I/R with sevoflurane only (sevoflurane trial); I/R with glucose and sevoflurane (combined trial). Control baseline FBF was taken in every trial before any intervention, and FBF was taken during intervention and post I/R.
|
Vitamin C and Glucose
To determine if vitamin C can restore the impairment of the endothelium (FBF) caused by the glucose (dextrose infusion). All subjects received glucose and I/R injury (ischemia), either with or without vitamin C. Control baseline FBF was taken in every trial before any intervention, and FBF was taken during intervention and post I/R.
|
Statin and Glucose
Volunteers ingested a 40 mg simvastatin (statin) pill for the two evenings prior to study day and the morning of the study to determine the effect of simvastatin on modulating the I/R injury during hyperglycemia (high glucose). Volunteers were studied with statin alone and with statin and glucose.
|
|---|---|---|---|
|
Overall Study
STARTED
|
26
|
16
|
17
|
|
Overall Study
COMPLETED
|
25
|
16
|
14
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
3
|
Reasons for withdrawal
| Measure |
Sevoflurane and Glucose
Endothelial function will be measured via forearm blood flow (FBF). Subjects may get I/R injury (ischemia) without glucose or sevoflurane (placebo trial); I/R with glucose only (glucose trial); I/R with sevoflurane only (sevoflurane trial); I/R with glucose and sevoflurane (combined trial). Control baseline FBF was taken in every trial before any intervention, and FBF was taken during intervention and post I/R.
|
Vitamin C and Glucose
To determine if vitamin C can restore the impairment of the endothelium (FBF) caused by the glucose (dextrose infusion). All subjects received glucose and I/R injury (ischemia), either with or without vitamin C. Control baseline FBF was taken in every trial before any intervention, and FBF was taken during intervention and post I/R.
|
Statin and Glucose
Volunteers ingested a 40 mg simvastatin (statin) pill for the two evenings prior to study day and the morning of the study to determine the effect of simvastatin on modulating the I/R injury during hyperglycemia (high glucose). Volunteers were studied with statin alone and with statin and glucose.
|
|---|---|---|---|
|
Overall Study
Failed arterial cannulation
|
1
|
0
|
3
|
Baseline Characteristics
Ischemia/Reperfusion Injury of Human Endothelium: Role of Glucose and Statins
Baseline characteristics by cohort
| Measure |
Sevoflurane and Glucose
n=26 Participants
Endothelial function will be measured via forearm blood flow (FBF). Subjects may get I/R injury (ischemia) without glucose or sevoflurane (placebo trial); I/R with glucose only (glucose trial); I/R with sevoflurane only (sevoflurane trial); I/R with glucose and sevoflurane (combined trial). Control baseline FBF was taken in every trial before any intervention, and FBF was taken during intervention and post I/R.
Glucose: 5% dextrose will be infused at 12ml/hr to a target of 200 mg/dl blood concentration in the experimental forearm for 60 min to prevent the anesthetic preconditioning (sevoflurane) protection against subsequent I/R injury.
Sevoflurane: 1 minimum alveolar concentration (MAC) for 20 min (after hour of glucose and before I/R) 26 volunteers were studied 67 times in this arm.
|
Vitamin C and Glucose
n=16 Participants
To determine if vitamin C can restore the impairment of the endothelium (FBF) caused by the glucose (dextrose infusion). All subjects received glucose and I/R injury (ischemia), either with or without vitamin C. Control baseline FBF was taken in every trial before any intervention, and FBF was taken during intervention and post I/R.
Placebo data were the placebo studies from the Sevoflurane and Glucose arm, when appropriate; new subjects (not enrolled in Sevoflurane and Glucose arm) underwent a separate placebo trial.
Glucose: 5% dextrose will be infused at 12ml/hr to a target of 200 mg/dl blood concentration in the experimental forearm for 60 min.
Vitamin C: 1 gm iv bolus injection 5 min before I/R injury 16 volunteers were studied 25 times in this arm.
|
Statin and Glucose
n=17 Participants
Volunteers ingested a 40 mg simvastatin (statin) pill for the two evenings prior to study day and the morning of the study to determine the effect of simvastatin on modulating the I/R injury during hyperglycemia (high glucose). Volunteers were studied with statin alone and with statin and glucose.
Placebo data were the placebo studies from the Sevoflurane and Glucose arm, when appropriate; new subjects (not enrolled in Sevoflurane and Glucose arm) underwent a separate placebo trial.
Glucose: 5% dextrose will be infused at 12ml/hr to a target of 200 mg/dl blood concentration in the experimental forearm for 60 min.
Statin: 40 mg of simvastatin 17 volunteers were studied 31 times in this arm.
|
Total
n=59 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
18-35 years old
|
26 participants
n=5 Participants
|
16 participants
n=7 Participants
|
17 participants
n=5 Participants
|
59 participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
33 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
26 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
26 participants
n=5 Participants
|
16 participants
n=7 Participants
|
17 participants
n=5 Participants
|
59 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline, Glucose Control, 15-min post ischemiaendothelial (forearm blood flow) responses to acetylcholine stimulation at baseline, and under conditions of high glucose before and after ischemia/reperfusion injury, and same with the addition of an intervention: sevoflurane (Arm 1), vitamin C (Arm 2), and high statin (Arm 3).
Outcome measures
| Measure |
Sevoflurane and Glucose
n=26 Participants
To determine the effectiveness of anesthetic preconditioning (APC) via sevoflurane to attenuate the I/R injury during the normal glucose state and during hyperglycemia.
|
Vitamin C and Glucose
n=16 Participants
To determine if vitamin C can restore the impairment of the endothelium caused by the dextrose infusion.
|
Statin and Glucose
n=17 Participants
To determine the effect of simvastatin on modulating the I/R injury during the normal glucose state and during hyperglycemia.
|
|---|---|---|---|
|
Forearm Blood Flow
Baseline
|
6.48 ml/100 ml tissue/min
Standard Error 0.86
|
9.2 ml/100 ml tissue/min
Standard Error 2.92
|
7.32 ml/100 ml tissue/min
Standard Error 1.06
|
|
Forearm Blood Flow
Control, Glucose
|
8.26 ml/100 ml tissue/min
Standard Error 1.00
|
9.2 ml/100 ml tissue/min
Standard Error 2.92
|
9.91 ml/100 ml tissue/min
Standard Error 1.43
|
|
Forearm Blood Flow
Post Ischemia, Glucose
|
7.10 ml/100 ml tissue/min
Standard Error 0.65
|
7.6 ml/100 ml tissue/min
Standard Error 2.42
|
7.00 ml/100 ml tissue/min
Standard Error 1.01
|
|
Forearm Blood Flow
Intervention Baseline
|
8.47 ml/100 ml tissue/min
Standard Error 0.82
|
8.84 ml/100 ml tissue/min
Standard Error 1.39
|
8.17 ml/100 ml tissue/min
Standard Error 1.06
|
|
Forearm Blood Flow
Control, after intervention
|
7.90 ml/100 ml tissue/min
Standard Error 0.84
|
9.3 ml/100 ml tissue/min
Standard Error 1.73
|
9.28 ml/100 ml tissue/min
Standard Error 1.34
|
|
Forearm Blood Flow
Post Ischemia, intervention
|
8.45 ml/100 ml tissue/min
Standard Error 1.18
|
9.91 ml/100 ml tissue/min
Standard Error 1.63
|
6.26 ml/100 ml tissue/min
Standard Error 0.82
|
Adverse Events
Sevoflurane & Glucose
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Vitamin C & Glucose
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Statins & Glucose
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
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place