Effect of Acupuncture to Endothelial Dysfunction Induced by Ischemia-reperfusion Injury (AURORAS)

Effect of Acupuncture to Endothelial Dysfunction Induced by Ischemia-reperfusion Injury Via Adenosine Triphosphate-sensitive Potassium Channels or Prostaglandin Pathway

Some studies suggest that acupuncture improve flow mediated dilation (FMD) that represents endothelial function, but no study has investigated whether acupuncture protects against ischemia and reperfusion (IR)-induced endothelial dysfunction in humans.

This is a prospective crossover study clinical trial. In the first crossover study, 20 healthy nonsmoking volunteers (25 to 40 years old) will be randomly assigned to acupuncture or control. Endothelium-dependent, FMD of the brachial artery will be measured before and after IR (15 minutes of ischemia at the level of the proximal upper arm followed by 15 minutes of reperfusion). Acupuncture will be performed from 10 minute after ischemia till the end time of reperfusion for 20 minutes. In the second single arm study, 16 volunteers are administered oral 5mg glibenclamide two hours before IR injury (n=8) or selective cox-2 inhibitor celecoxib 200mg twice a day for 5 days to know what mechanism is responsible for acupuncture effect on IR injury. FMD measurements and acupuncture intervention during IR injury are same as above mentioned.

Study Overview

• Status: Unknown
• Conditions: Healthy
• Intervention / Treatment: Device: Active acupuncture; Drug: Euglucon 5mg; Drug: Celebrex 200mg; Device: Sham acupuncture

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 130-701
    • Recruiting
    • Kyung Hee University Medical Center
    • Contact: Weon Kim, Professor; Phone Number: 82-2-958-8176; Email: mylovekw@hanmail.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• healthy volunteer age 25 to 40 years
• non-smoker

Exclusion Criteria:

• hypertension (>140/90 mmHg), diabetes any cardiovascular disease kidney disease thyroid disease cerebrovascular disease liver disease (bilirubin level >2 mg/dl) pregnancy body mass index >25 kg/m2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: active acupuncture; The participants in this group receive real acupuncture treatment at first. Afterwards crossover study is scheduled to be performed.	Device: Active acupuncture; Active acupuncture treatment group receive electroacupuncture (EA). For EA treatment, unilateral acupuncture meridian point Pericardium5 (PC5), Pericardium6 (PC6), Stomach36 (ST36), and Stomach37 (ST37) are chosen. Disposable, sterile needles and low frequency electrical stimulator (ES-160, ITO, Japan) are used. Each needle is inserted to the depth of 2cm with a 90 degree angle. Thereafter, needles are connected with the pole and electrical stimulation is applied with 2 Hertz continuous wave current. After FMD measurement, a pneumatic cuff placed above the upper arms is inflated to 200 mmHg for 15 minutes. The cuff is then deflated, and 15 minutes of reperfusion is allowed before FMD measurement again. Acupuncture is performed from after ten minutes of ischemia till end time of reperfusion; Drug: Euglucon 5mg; 8 healthy volunteers are administered 5 mg of glibenclamide (Euglucon, Roche Pharma) 3 hour before FMD measurement. This dosage has previously been shown to be able to completely inhibit forearm KATP channels. With the glibenclamide administration, a 10% dextrose infusion is started and titrated to maintain blood sugar levels between 80 and 120 mg/dL throughout the study period. 3 hours after glibenclamide administration, the subjects undergo FMD measurement before and after ischemia reperfusion injury. During ischemia reperfusion period, active acupuncture treatment is performed for 20 minutes like above method.; Other Names: Glibenclamide; Drug: Celebrex 200mg; 8 healthy volunteers are administered celecoxib, a selective COX-2 inhibitor, 200 mg twice daily for 5 days. Last dose of celecoxib is administered at morning. Volunteers undergo FMD measurements before and after ischemia reperfusion injury in that morning of last dose of celecoxib. During ischemia reperfusion period, active acupuncture treatment is performed for 20 minutes like above method; Other Names: Celecoxib
Sham Comparator: Sham acupuncture; The participants in this group receive sham acupuncture treatment at first. afterwards crossover study is scheduled to be performed	Device: Sham acupuncture; For sham intervention, nonacupuncture points are used. Electrical acupuncture is connected but electrical stimulation is not given to sham acupuncture group. Volunteers undergo FMD measurement and acupuncture like above methods.
Experimental: Euglycon; Glibenclamide (Euglucon, Roche Pharma) is administered 3 hours before FMD measurement.	Device: Active acupuncture; Active acupuncture treatment group receive electroacupuncture (EA). For EA treatment, unilateral acupuncture meridian point Pericardium5 (PC5), Pericardium6 (PC6), Stomach36 (ST36), and Stomach37 (ST37) are chosen. Disposable, sterile needles and low frequency electrical stimulator (ES-160, ITO, Japan) are used. Each needle is inserted to the depth of 2cm with a 90 degree angle. Thereafter, needles are connected with the pole and electrical stimulation is applied with 2 Hertz continuous wave current. After FMD measurement, a pneumatic cuff placed above the upper arms is inflated to 200 mmHg for 15 minutes. The cuff is then deflated, and 15 minutes of reperfusion is allowed before FMD measurement again. Acupuncture is performed from after ten minutes of ischemia till end time of reperfusion; Drug: Euglucon 5mg; 8 healthy volunteers are administered 5 mg of glibenclamide (Euglucon, Roche Pharma) 3 hour before FMD measurement. This dosage has previously been shown to be able to completely inhibit forearm KATP channels. With the glibenclamide administration, a 10% dextrose infusion is started and titrated to maintain blood sugar levels between 80 and 120 mg/dL throughout the study period. 3 hours after glibenclamide administration, the subjects undergo FMD measurement before and after ischemia reperfusion injury. During ischemia reperfusion period, active acupuncture treatment is performed for 20 minutes like above method.; Other Names: Glibenclamide
Experimental: Celebrex; Celebrex(celecoxib, pfizer) 200mg twice daily is administered for 5 days before FMD measurement.	Device: Active acupuncture; Active acupuncture treatment group receive electroacupuncture (EA). For EA treatment, unilateral acupuncture meridian point Pericardium5 (PC5), Pericardium6 (PC6), Stomach36 (ST36), and Stomach37 (ST37) are chosen. Disposable, sterile needles and low frequency electrical stimulator (ES-160, ITO, Japan) are used. Each needle is inserted to the depth of 2cm with a 90 degree angle. Thereafter, needles are connected with the pole and electrical stimulation is applied with 2 Hertz continuous wave current. After FMD measurement, a pneumatic cuff placed above the upper arms is inflated to 200 mmHg for 15 minutes. The cuff is then deflated, and 15 minutes of reperfusion is allowed before FMD measurement again. Acupuncture is performed from after ten minutes of ischemia till end time of reperfusion; Drug: Celebrex 200mg; 8 healthy volunteers are administered celecoxib, a selective COX-2 inhibitor, 200 mg twice daily for 5 days. Last dose of celecoxib is administered at morning. Volunteers undergo FMD measurements before and after ischemia reperfusion injury in that morning of last dose of celecoxib. During ischemia reperfusion period, active acupuncture treatment is performed for 20 minutes like above method; Other Names: Celecoxib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The difference of endothelial function	Endothelial function is measured by brachial flow mediated dilation (FMD). Is there a difference of forearm FMD achieved following ischemia reperfusion injury between acupuncture and control group	4 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The difference of endothelial function	Endothelial function is also measured by brachial flow mediated dilation (FMD). Is the difference of endothelial function mediated by acupuncture hampered by Triphosphate-Sensitive Potassium (KATP) Channels inhibitor glibenclamide or selective cox-2 inhibitor celebrex if acupuncture could improve flow mediated dilation after ischemia reperfusion injury? It is performed for knowing which mechanisms are involved in this improvement if acupuncture could improve flow mediated dilation after ischemia reperfusion injury?	4 week

Collaborators and Investigators

• Sponsor: Kyunghee University Medical Center
• Collaborators: Ministry of Health & Welfare, Korea
• Investigators: Principal Investigator: Weon Kim, Kyunghee University Medical Center

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Anticipated): October 1, 2014
• Study Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: September 5, 2014
• First Submitted That Met QC Criteria: September 29, 2014
• First Posted (Estimate): October 2, 2014

Study Record Updates

• Last Update Posted (Estimate): October 2, 2014
• Last Update Submitted That Met QC Criteria: September 29, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: volunteer; BMI(25 kg/m2)
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications; Ischemia; Reperfusion Injury; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Celecoxib; Glyburide
• Other Study ID Numbers: HI13C0580-2