Effects of Ischemic Preconditioning on Conditioned Pain Modulation and Heart Rate Variability in Knee Osteoarthritis

May 27, 2025 updated by: Franciele Marques Vanderle, Paulista University

Effects of Ischemic Preconditioning on Conditioned Pain Modulation and Heart Rate Variability in Women With Knee Osteoarthritis: Placebo-Controlled Randomized Clinical Trial

Introduction: Musculoskeletal disorders have affected approximately 1.3 billion people worldwide. Evidence shows that chronic diseases and musculoskeletal conditions often occur together, and among them it is estimated that more than 240 million people worldwide have symptomatic osteoarthritis (OA) and activity limitation, which is a major contributor to chronic pain and changes central in pain processing. It is known that physical exercise (active approach to treatment) and manual therapy (passive approach) are capable of intervening in the pain processing system, but passive approaches have been little investigated. Among them, little is known about the effect of ischemic preconditioning (IPC) for pain management and its impact on conditioned pain modulation (CPM) and cardiac autonomic control. There is no evidence that IPC causes systemic hypoalgesia and increased vagal modulation, so this provides a rationale for study. Objectives: To analyze the acute effect of IPC on local pain, CPM and cardiac autonomic control in women with knee OA and observe whether there is a correlation between them. Methods: Double-blind, placebo-controlled, randomized clinical trial. Participants will be divided into IPC or placebo groups. Outcomes evaluated: CPM and cardiac autonomic modulation. Comparisons will be performed using Generalized Mixed Linear Models fitted to the data. For correlation, the Pearson or Spearman correlation test will be used according to the normality of the data. All analyzes will assume a significance level of p<0.05.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
44

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Brazil
    • SP
      • Presidente Prudente, SP, Brazil, 55
        • Franciele Marques Vanderlei

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

45 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Medical diagnosis for uni or bilateral OA of the tibiofemoral joint (grade II or superior Kellgren-Lawrence radiographic changes);
  • Not having systemic rheumatic diseases such as fibromyalgia, rheumatoid arthritis, systemic lupus erythematosus;
  • Not having total knee arthroplasty, knee ligament injury, history of knee surgery;
  • Not having heart disease, congestive heart failure, or a history of acute myocardial infarction (except those with hypertension);
  • Not having diagnosis of neurological, metabolic, endocrine disorder, respiratory disease;
  • Not being an alcoholic or smoker;
  • Not use drugs that influence cardiac autonomic modulation (beta-blocker);
  • Not having one or more predisposing risk factors for thromboembolism.

Exclusion Criteria:

  • Use anti-inflammatory drugs or analgesics 24 hours before the test;
  • Perform physical activity;
  • Consume alcohol;
  • Perform therapeutic treatments for pain relief;
  • Errors in capturing the RR intervals;
  • Want to leave the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Ischemic Preconditioning (n= 22)

The IPC protocol will be applied in the proximal region of the thigh of the limb with knee osteoarthritis and if both knees are affected, it will be applied to the knee with the greatest complaint of pain.

Participants will be relaxed and comfortably seated. The same cuff used to determine the total occlusion pressure (TOP) will be used and the protocol will consist of four cycles of total ischemia (according to the TOP value determined individually) of five minutes, followed immediately by four cycles of five minutes of vascular reperfusion (0 mmHg ), totaling 40 minutes.
Device: Ischemic Preconditioning
The Ischemic Preconditioning (IPC) is characterized by the application of brief periods of circulatory occlusion (ischemia) and reperfusion of a limb in the minutes to hours that precede the exercise through the insufflations and deflations of a pressure cuff.
Placebo Comparator: Placebo (n= 22)
The placebo protocol will be performed on the lower limb with knee osteoarthritis and if both knees are affected, it will be applied to the knee with the greatest complaint of pain. Participants will perform a protocol similar to the IPC, but during the four cycles of five minutes of occlusion, the cuffs will only be inflated with 10mmHg so as not to cause arterial or venous occlusion, alternating with four cycles of five minutes of reperfusion (0 mmHg).
Device: Ischemic Preconditioning
The Ischemic Preconditioning (IPC) is characterized by the application of brief periods of circulatory occlusion (ischemia) and reperfusion of a limb in the minutes to hours that precede the exercise through the insufflations and deflations of a pressure cuff.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Conditioned Pain Modulation
Time Frame: Change from baseline after intervention.
Conditioned pain modulation is a dynamic measure capable of evaluating endogenous pain inhibition using a "pain-by-pain inhibition" model in which pain in a local area (test stimulus) is inhibited by a second concomitant pain (pain stimulus) conditioning). In this study, the test stimulus will be performed through the pressure pain threshold using algometer and the conditioning stimulus will be performed by immersing the hand in cold water, using the cold pressor test - CPT.
Change from baseline after intervention.
Cardiac Autonomic Modulation
Time Frame: Change from baseline after intervention.
The assessment of cardiac autonomic modulation will be performed using HRV through the capture of heart rate beat to beat (RR intervals) using a heart rate monitor (Polar Electro Oy, Kempele, Finland - model V800) which is a validated equipment.
Change from baseline after intervention.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Paulista University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 15, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 15, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 15, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 30, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 20, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 28, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 31, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 27, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 5543/2021

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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