HyperglycemiaNCT00995670
Ischemia/Reperfusion Injury of Human Endothelium: Role of Glucose and Statins
A study testing 5% dextrose, Vitamin C and Simvastatin in people with Hyperglycemia, run by US Department of Veterans Affairs at 1 site in United States.
Trial summary
Anesthetic preconditioning (APC, a brief exposure to an anesthetic gas) has become an area of intense research interest because of its ability to protect tissue and organs from injury resulting from a cessation of blood flow and then a re-establishment of flow. The blood vessel lining plays a key role in this injury. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Hyperglycemia
- What is being tested?
- 5% dextrose, Vitamin C and Simvastatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2010to Sep 2013
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Young, healthy volunteers, 18-35 yr of age;
- Females will be studied at the same phase of their estrous cycle in each protocol.
Who cannot join
- Beta-blocker therapy or any medication that might interfere with vascular responses;
- Pregnant or lactating women;
- Substance abusers;
- Smokers;
- Anyone with cardiovascular, renal, or other systemic disease including hypertension and/or diabetes;
- Also excluded are volunteers with family history of malignant hyperthermia, or significant gastro-esophageal reflux.
Trial locations and contacts
1 site in 1 country.
United States1 site
Zablocki VA Medical Center, Milwaukee
Milwaukee, Wisconsin, 53295-1000
About this study
Anesthetic preconditioning (APC, a brief exposure to an anesthetic gas) has become an area of intense research interest because of its ability to protect tissue and organs from injury resulting from a cessation of blood flow and then a re-establishment of flow. The blood vessel lining plays a key role in this injury. This research will examine, in human volunteers, several important modifiers of APC in human blood vessels: high blood sugar, vitamin C, and statin drugs. Thus, the proposed studies will advance the investigators' understanding of mechanisms of this injury in humans and explore important modifiers of APC protection from injury.
Read the detailed description
Injury to vital organs and tissue can occur when blood flow is stopped and then re-established. This happens in a variety of clinical situations and contributes to poor outcomes. A newer concept of protection from this injury by an anesthetic drug might occur because of the effect of the volatile anesthetics on the tissue that lines blood vessels. Thus, a brief exposure to a volatile anesthetic before a cessation of blood flow, called anesthetic preconditioning (APC), can substantially reduce the resulting injury to the lining of the blood vessels. In animal models, high levels of blood sugar block this protection, while cholesterol lowering drugs (statins) restore the protection and may independently protect blood vessel lining from injury. The interactions of high blood sugar and statin drugs on the blood vessel reaction to APC and a subsequent 20-min cessation of blood flow to the forearm will be studied in humans. In addition, the involvement of reactive oxygen species (ROS) in the harmful effects of high blood sugar and the beneficial effects of statins will be explored. The following four hypotheses will be studied: 1) high blood sugar blocks the anesthetic protection of blood vessels from injury in a dose and time dependent manner; 2) reactive oxygen species are involved in the inhibition of APC by high blood sugar; 3) statins modulate injury in a dose related manner; and 4) statins reduce high blood sugar inhibition of APC.
A standard model to evaluate forearm blood vessel function will be used. Thin rubber-band-like strain gauges will be strapped around each forearm and the change in their stretch during a variety of interventions on the experimental arm (the other arm will not receive any interventions and will be the control arm) will be measured. These interventions will allow the investigator to determine whether the hypotheses listed above are true. During all studies, there will be a 20-min arrest of the forearm circulation. Additional effects of injury, APC, high blood sugar, and statins will be determined by evaluating blood vessel inflammatory responses from "markers" in blood samples taken before and after I/R injury. Several studies will involve varying the forearm blood glucose concentration for brief (30 min) to longer (2 hours) periods prior to APC and injury. The ROS scavenger vitamin C will be used to evaluate the role of ROS in adverse effects of high blood sugar. There are several other studies that will continue to seek the mechanism of action of this effect via the use of other drug interactions.
- Conditions
- Hyperglycemia
- Being tested
- 5% dextrose, Vitamin C, Simvastatin, Sevoflurane
- Keywords
- hyperglycemia, statin, blood vessels, ischemic preconditioning, Anesthesia, inhalational, endothelium, 5% dextrose
- Medical subject headings
- Hyperglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5% dextroseDrug
Also called Glucose
Glucose is infused to prevent the anesthetic preconditioning (sevoflurane) protection against subsequent ischemia/reperfusion injury.
Vitamin CDrug
Also called Vit C
Vitamin C is intended to restore the impairment of the endothelium caused by the dextrose infusion.
SimvastatinDrug
Also called Statin
Simvastatin will be ingested to determine the efficacy of a statin to modulate the forearm response to glucose.
SevofluraneDrug
Also called Sevo
Sevoflurane will be given to attenuate or prevent the I/R injury during glucose.
| Study group | Role | What they receive |
|---|---|---|
| Sevoflurane and Glucose | Experimental | Endothelial function will be measured via forearm blood flow (FBF). Subjects may get I/R injury (ischemia) without glucose or sevoflurane (placebo); I/R with glucose only (glucose trial); I/R with sevoflurane only (sevo trial); I/R with glucose and sevoflurane (combo trial). 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 12 ml/hr to a target of 200 mg/dl blood concentration in the experimental forearm for 1 hr to prevent the anesthetic preconditioning (sevoflurane) protection against subsequent I/R injury.
Sevoflurane: 1 minimum alveolar concentration (MAC) for 20 min (after 1 hr glucose and before I/R) 26 volunteers were studied 67 times in this arm. Receives: Drug: 5% dextrose; Drug: Sevoflurane |
| Vitamin C and Glucose | Experimental | 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. Receives: Drug: 5% dextrose; Drug: Vitamin C |
| Statins and Glucose | Experimental | 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. Receives: Drug: 5% dextrose; Drug: Simvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Forearm Blood Flow
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).
Measured: Baseline, Glucose Control, 15-min post ischemia
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2009 (estimated)
- Study startMar 2010
- Primary completionSep 2013
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HyperglycemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- US Department of Veterans Affairs
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Thomas J Ebert, MD PhD, Principal investigator, Zablocki VA Medical Center, Milwaukee
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00995670
- Sponsor's protocol ID
- CARA-023-09S
- Status last verified
- Mar 2015
- First submitted
- 13 Oct 2009
- Last updated
- 17 Mar 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ischemia/Reperfusion Injury of Human Endothelium: Role of Glucose and Statins
- ClinicalTrials.gov ID
- NCT00995670
- Acronym / sponsor ID
- CARA-023-09S
- Conditions
- Hyperglycemia
- Keywords
- hyperglycemia, statin, blood vessels, ischemic preconditioning, Anesthesia, inhalational, endothelium, 5% dextrose
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- US Department of Veterans AffairsUS federal agency
- Study start
- Mar 2010
- Primary completion
- Sep 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 15 Oct 2009 (estimated)
- Results
- Posted 17 Mar 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Anesthetic preconditioning (APC, a brief exposure to an anesthetic gas) has become an area of intense research interest because of its ability to protect tissue and organs from injury resulting from a cessation of blood flow and then a re-establishment of flow. The blood vessel lining plays a key role in this injury. This research will examine, in human volunteers, several important modifiers of APC in human blood vessels: high blood sugar, vitamin C, and statin drugs. Thus, the proposed studies will advance the investigators' understanding of mechanisms of this injury in humans and explore important modifiers of APC protection from injury.
Detailed description
Injury to vital organs and tissue can occur when blood flow is stopped and then re-established. This happens in a variety of clinical situations and contributes to poor outcomes. A newer concept of protection from this injury by an anesthetic drug might occur because of the effect of the volatile anesthetics on the tissue that lines blood vessels. Thus, a brief exposure to a volatile anesthetic before a cessation of blood flow, called anesthetic preconditioning (APC), can substantially reduce the resulting injury to the lining of the blood vessels. In animal models, high levels of blood sugar block this protection, while cholesterol lowering drugs (statins) restore the protection and may independently protect blood vessel lining from injury. The interactions of high blood sugar and statin drugs on the blood vessel reaction to APC and a subsequent 20-min cessation of blood flow to the forearm will be studied in humans. In addition, the involvement of reactive oxygen species (ROS) in the harmful effects of high blood sugar and the beneficial effects of statins will be explored. The following four hypotheses will be studied: 1) high blood sugar blocks the anesthetic protection of blood vessels from injury in a dose and time dependent manner; 2) reactive oxygen species are involved in the inhibition of APC by high blood sugar; 3) statins modulate injury in a dose related manner; and 4) statins reduce high blood sugar inhibition of APC.
A standard model to evaluate forearm blood vessel function will be used. Thin rubber-band-like strain gauges will be strapped around each forearm and the change in their stretch during a variety of interventions on the experimental arm (the other arm will not receive any interventions and will be the control arm) will be measured. These interventions will allow the investigator to determine whether the hypotheses listed above are true. During all studies, there will be a 20-min arrest of the forearm circulation. Additional effects of injury, APC, high blood sugar, and statins will be determined by evaluating blood vessel inflammatory responses from "markers" in blood samples taken before and after I/R injury. Several studies will involve varying the forearm blood glucose concentration for brief (30 min) to longer (2 hours) periods prior to APC and injury. The ROS scavenger vitamin C will be used to evaluate the role of ROS in adverse effects of high blood sugar. There are several other studies that will continue to seek the mechanism of action of this effect via the use of other drug interactions.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Sevoflurane and Glucose | Experimental | Drug: 5% dextrose, Drug: SevofluraneEndothelial function will be measured via forearm blood flow (FBF). Subjects may get I/R injury (ischemia) without glucose or sevoflurane (placebo); I/R with glucose only (glucose trial); I/R with sevoflurane only (sevo trial); I/R with glucose and sevoflurane (combo trial). 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 12 ml/hr to a target of 200 mg/dl blood concentration in the experimental forearm for 1 hr to prevent the anesthetic preconditioning (sevoflurane) protection against subsequent I/R injury. Sevoflurane: 1 minimum alveolar concentration (MAC) for 20 min (after 1 hr glucose and before I/R) 26 volunteers were studied 67 times in this arm. |
| Vitamin C and Glucose | Experimental | Drug: 5% dextrose, Drug: Vitamin CTo 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. |
| Statins and Glucose | Experimental | Drug: 5% dextrose, Drug: SimvastatinVolunteers 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. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Young, healthy volunteers, 18-35 yr of age;
- Females will be studied at the same phase of their estrous cycle in each protocol.
Key exclusion criteria (6 listed)
- Beta-blocker therapy or any medication that might interfere with vascular responses;
- Pregnant or lactating women;
- Substance abusers;
- Smokers;
- Anyone with cardiovascular, renal, or other systemic disease including hypertension and/or diabetes;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 5% dextroseAlso: GlucoseGlucose is infused to prevent the anesthetic preconditioning (sevoflurane) protection against subsequent ischemia/reperfusion injury. | Drug | Sevoflurane and Glucose, Statins and Glucose, Vitamin C and Glucose |
| Vitamin CAlso: Vit CVitamin C is intended to restore the impairment of the endothelium caused by the dextrose infusion. | Drug | Vitamin C and Glucose |
| SimvastatinAlso: StatinSimvastatin will be ingested to determine the efficacy of a statin to modulate the forearm response to glucose. | Drug | Statins and Glucose |
| SevofluraneAlso: SevoSevoflurane will be given to attenuate or prevent the I/R injury during glucose. | Drug | Sevoflurane and Glucose |
Primary outcome
Forearm Blood Flow
Time frame: Baseline, Glucose Control, 15-min post ischemia
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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Hyperglycemia
Recruiting
Effects of Lean Pork Loin Intake on Protein Homeostasis and Glucose Regulation in Prediabetic Adults
Hyperglycaemia (Non Diabetic), Prediabetes
Not yet recruitingObservational study
Evaluation of the Clinical Spectrum of Diabetes and Obesity in Youth and Adults
Obesity, Diabetes
RecruitingObservational study
Food-i-Sense Analytics: Integrating AI Into Continuous Glucose Monitoring Data Analysis for Precision Nutrition.
Prediabetes (Insulin Resistance, Impaired Glucose Tolerance), Artificial Intelligence Mobile Application
Not yet recruiting
Multimodal AI-Driven Out-of-Hospital Management for Hypertension and Cardiometabolic Risk
Hypertension, Hyperglycemia
Recruiting
Hypothalamic GLP-1 Response in Healthy Weight and Obesity
Obesity, Normal Weight
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas J Ebert, MD PhD principal investigator
Zablocki VA Medical Center, Milwaukee
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 5% dextrose, Vitamin C and Simvastatin in people with Hyperglycemia, run by US Department of Veterans Affairs at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Mar 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Forearm Blood Flow (time frame: Baseline, Glucose Control, 15-min post ischemia). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2015.