Remote Ischemic Preconditioning Mechanism Study

Remote Ischemic Preconditioning Effects on Central and Peripheral Sensitization in Healthy Volunteers-A Pilot Study

This research is being done because pain is a significant problem for patients with a variety of medical problems and following surgery or traumatic injury. Currently available pain medications may not relieve all types of pain or may relieve pain only at doses that produce side effects and potential complications.

Although Remote Ischemic Preconditioning (RIPC) appears promising, there remain several unanswered questions about how it works. This research trial will help determine how RIPC may activate the bodies natural pain control system. The goals of this study are to see if RIPC has any effect 1) on a small area of skin that will be expose to a small amount of UV- B radiation (a mild sunburn), 2) on acute thermal heat temperatures that will be applied to skin, and 3) on the sunburn-like sensation to light touch after putting capsaicin cream (the active ingredient in hot chili peppers) on skin.

Remote ischemic preconditioning is done by inflating a balloon (very similar to a blood pressure cuff) on the leg until it blocks blood flow for a few minutes. The cuff is then deflated and blood flow resumes. The process is repeated up to three times. This procedure causes the body to increase its natural pain relief system that may help to decrease the amount of postsurgical pain.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Device: Remote Ischemic Preconditioning, Capsaicin, UV-B

Detailed Description

The purpose of this pilot study is to determine whether RIPC effects peripheral sensitization, central sensitization or both and determine effect size since there is no data regarding the presumed effect. These issues cannot be easily sorted out in patients experiencing postoperative pain and hypersensitivity, since surgery affects both components. In order to address this purpose the investigators will examine, in healthy volunteers, the effect of RIPC on a manipulation which generates hypersensitivity by an exclusive peripheral mechanism (ultraviolet B (UV-B) burn) and a manipulation which generates hypersensitivity by an exclusive central mechanism (topical capsaicin). Understanding the sites at which RIPC reduces the amplification of pain after injury will be useful in determining where it would be most logically applied clinically and in guiding preclinical mechanistic studies.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • WakeForestUBMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• healthy volunteers of both sexes ASA 1 or II classification
• between the ages of 18-55
• weighing less than 250 pounds
• without chronic pain
• not taking analgesics
• off caffeine for 2 days.

Exclusion Criteria:

• pregnancy
• allergy to capsaicin
• lower extremity vascular insufficiency
• active treatment for DVT
• severe thigh pain
• taking psychotropic medications, including anti-depressants.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Capsaicin, UV-B, RIPC	Device: Remote Ischemic Preconditioning, Capsaicin, UV-B; The participants will have one disposable tourniquet applied to the left mid thigh by research personnel. The participants will then be randomized to the treatment group or sham group. The treatment group will receive 3 cycles of RIPC to the left lower leg by occluding blood flow at the thigh with a pneumatic cuff. Each cycle will consist of 5 minutes of ischemia by inflating the cuff to 300 mmHg followed by 5 minutes of reperfusion. The sham group will have the cuff inflated to no more than 15mmHg for three cycles as described above. Areas of hypersensitivity and allodynia will be obtained every 40 min for 280 min following the end of capsaicin application.
Sham Comparator: Capsaicin, UV-B	Device: Remote Ischemic Preconditioning, Capsaicin, UV-B; The participants will have one disposable tourniquet applied to the left mid thigh by research personnel. The participants will then be randomized to the treatment group or sham group. The treatment group will receive 3 cycles of RIPC to the left lower leg by occluding blood flow at the thigh with a pneumatic cuff. Each cycle will consist of 5 minutes of ischemia by inflating the cuff to 300 mmHg followed by 5 minutes of reperfusion. The sham group will have the cuff inflated to no more than 15mmHg for three cycles as described above. Areas of hypersensitivity and allodynia will be obtained every 40 min for 280 min following the end of capsaicin application.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Areas of hyperalgesia and allodynia to mechanical stimuli.	Hyperalgesia will be measured with vonFrey fibers and allodynia will be measured with a cotton wisp. The area will be measured in cm2.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain intensity and unpleasantness to mechanical stimuli	Using a Visual Analog Sliding Scale the intensity and unpleasantness will be measured in centimeters.	24 hours
Presence of parathesias where RIPC was used	After a brief tourniquet application I fully expect participants to have some degree of parasthesias. Using a standard rating scale I will record and report this.	24 hours

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Investigators: Principal Investigator: Scott A Miller, MD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2012
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): April 30, 2017

Study Registration Dates

• First Submitted: February 3, 2012
• First Submitted That Met QC Criteria: February 23, 2012
• First Posted (Estimate): March 1, 2012

Study Record Updates

• Last Update Posted (Actual): August 10, 2018
• Last Update Submitted That Met QC Criteria: August 8, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Nociception; Remote Ischemic Preconditioning; Central Sensitization; Peripheral Sensitization
• Additional Relevant MeSH Terms: Pathologic Processes; Ischemia; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Dermatologic Agents; Antipruritics; Capsaicin
• Other Study ID Numbers: 00019284

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No