Role of Sympathetic Activation in Ischemia Reperfusion Injury

This study is designed to assess the effect of forearm ischemia-reperfusion injury on sympathetic nerve activity. To determine whether reduced sympathetic responsiveness is a contributor to the protective effects of remote ischemic preconditioning. In addition it will assess whether pharmacologic inhibition of the sympathetic nervous system can ameliorate ischemia reperfusion injury induced endothelial dysfunction.

Study Overview

• Status: Completed
• Conditions: Central Sympathetic Nervous System Diseases
• Intervention / Treatment: Other: placebo; Drug: Moxonidine 0.2 MG

Detailed Description

This is a randomized single blind study where subjects will be allocated to undergo one of the 4 protocols. Participants will be given placebo or 0.2mg of Moxonidine to take orally 20 minutes prior to the first endothelial function measurement.

This medication acts by reducing the activity of nerves believed to be involved in the conditioning process. The placebo pill, designed to have no effect, will be used as a comparison. Comprehensive tests will occur which include Microneurography, Endothelial function ,Blood Sampling, Temporary block of arm blood flow and Remote conditioning

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Perth, Australia
    • Dobney Hypertension Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• healthy males, not on any medication, free of any history of metabolic, cardiovascular or cerebrovascular disease.

Exclusion Criteria:

• smoker

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: SINGLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: No conditioning + placebo; Participants will be given placebo to take orally 20 minutes prior to the first endothelial function measurement without conditioning tests.	Other: placebo; Subjects will be allocated to undergo conditioning or non conditioning assigned in a randomized order. Participants will be given placebo or 0.2mg of Moxonidine to take orally 20 minutes prior to the first endothelial function measurement.
EXPERIMENTAL: No conditioning + moxonidine; Participants will be given moxonidine to take orally 20 minutes prior to the first endothelial function measurement without conditioning tests.	Drug: Moxonidine 0.2 MG; Subjects will be allocated to undergo conditioning or non conditioning assigned in a randomized order. Participants will be given placebo or 0.2mg of Moxonidine to take orally 20 minutes prior to the first endothelial function measurement.
EXPERIMENTAL: Remote pre-conditioning + placebo; Participants will be given placebo to take orally 20 minutes prior to the first endothelial function measurement with conditioning tests.	Other: placebo; Subjects will be allocated to undergo conditioning or non conditioning assigned in a randomized order. Participants will be given placebo or 0.2mg of Moxonidine to take orally 20 minutes prior to the first endothelial function measurement.
EXPERIMENTAL: Remote pre-conditioning + moxonidine; Participants will be given moxonidine to take orally 20 minutes prior to the first endothelial function measurement with conditioning tests.	Drug: Moxonidine 0.2 MG; Subjects will be allocated to undergo conditioning or non conditioning assigned in a randomized order. Participants will be given placebo or 0.2mg of Moxonidine to take orally 20 minutes prior to the first endothelial function measurement.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in muscle sympathetic nerve activity	Muscle sympathetic nerve activity assessed by microneurography	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endothelial Function using the EndoPat2000 device	Endothelial Function testing involves the measurement of pulse amplitude from the tip of each index finger at rest and after a period of occlusion using an arm cuff that is manually inflated to a level above that of the participant's Blood Pressure (BP).	2 days

Collaborators and Investigators

• Sponsor: Royal Perth Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 8, 2015
• Primary Completion (ACTUAL): March 1, 2022
• Study Completion (ACTUAL): March 1, 2022

Study Registration Dates

• First Submitted: July 16, 2020
• First Submitted That Met QC Criteria: July 16, 2020
• First Posted (ACTUAL): July 21, 2020

Study Record Updates

• Last Update Posted (ACTUAL): September 29, 2022
• Last Update Submitted That Met QC Criteria: September 28, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Ischemia; re-perfusion; Remote conditioning
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications; Ischemia; Nervous System Diseases; Reperfusion Injury; Autonomic Nervous System Diseases; Antihypertensive Agents; Moxonidine
• Other Study ID Numbers: REG 15-021

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No