Randomized Controlled Trial of Efficacy and Safety of Local Anesthetics and Steroids for Chronic Peripheral Post-traumatic Neuropathic Pain (RESPERIST)

March 23, 2020 updated by: Anuj Bhatia, University Health Network, Toronto

A Multi-center Randomized Controlled Trial of Efficacy and Safety of Perineural Local Anesthetics and Steroids for Chronic Peripheral Post-traumatic Neuropathic Pain: The Resperist Study

The purpose of this study is to evaluate three different injectable solutions used to block ankle nerves to manage ankle pain. The current standard of medical care is to inject a combination of local anesthetics and steroids around injured nerves. There is evidence that injection of local anesthetic (without the steroid) can calm the injured nerve and provide pain relief from a few days up to a few months. Injection of sterile salt water also has the potential to provide pain relief by breaking scar tissue around the nerve thereby relieving compression. Injections of local anesthetic and steroids around injured nerves have been used for many years to provide relief of pain but the specific reason is not well known for this benefit.

There are three possibilities: 1) Steroids can reduce inflammation and calm the nerves, 2) local anesthetics can have similar actions but with shorter duration (few days), and 3) injection of any solution can break scarring around an injured/compressed nerve.

The study will compare pain relief and possible adverse effects from these three different solutions. This study will help provide definitive answers regarding pain relief and possible adverse effects of the three solutions. This, in turn, will determine the best possible option for injection in patients with nerve-related injury pain.

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.

Detailed Description

This project is a randomized controlled trial with the aim of comparing efficacy of image (ultrasound)-guided administration of perineural combination of steroids and local anesthetic (current standard of care) against perineural local anesthetic (LA) or saline in providing sustained analgesic benefit in people with chronic neuropathic pain (NP) of the foot and ankle.

The study design will be multi-center, prospective, concealed, blinded, parallel group trial with three groups, block randomization (blocks of six participants) and allocation in a 2:2:2 ratio. Study participants and outcome evaluators will be blinded to treatment assignments.

Participants will be randomly assigned to one of the three groups to receive two US-guided injections (at an interval of one to two weeks) of one of the following around one or more of the five nerves innervating the foot and ankle:

The initial procedure will be repeated after one to two weeks unless clinical circumstances dictate otherwise (that is, the patient declined a second injection because of increase in pain or satisfaction with pain relief). The rationale for the repeat procedure is to allow possible benefit from a cumulative effect of the procedures and/or the injectates. Between the first injection and first follow-up visit, no patient will be allowed any additional therapeutic interventions. Nerves to be targeted by the injection will be decided by the treating physician based on area of the foot and ankle that displays features of neuropathic pain. Each injection of study medications will be preceded by subcutaneous injections of 1 mLs of LA (2% lidocaine) at each of the injection sites. This will reduce discomfort of the study participants from the injections. The subcutaneous LA will also cause numbness of the skin and this will ensure blinding of participants to their group allocation. Two ultrasound-guided procedures will be performed at weekly intervals over two weeks. The US-guided technique for performing these procedures has been described in previous studies from our center.22 Conservative measures (oral analgesics, physiotherapy) will continue during the study. Fasting blood glucose will be measured at baseline and at one month following the interventions. Systolic and diastolic blood pressure (with participant sitting for at least 5 minutes prior to the measurement) values will be recoded as a mean of three consecutive readings at baseline and at one month following the interventions. Cross-sectional area (CSA) of tibial nerve at 3 cm proximal to cephalad edge of medial malleolus will also be measured prior to the first procedure and prior to the second procedure in participants with pain in distribution of the tibial nerve. Change in CSA (if any) will be correlated with analgesic response to perineural injections because decrease in CSA may indicate reduction in edema of the nerve.

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.
3

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.
  • Phase 3

Contacts and Locations

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

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5T 2S8
        • Toronto Western Hospital

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

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Pain in foot in neuro-anatomically congruent location following trauma (including surgery) for more than three months
  2. Physician-reported DN4 scoring confirming neuropathic pain (score >3/10)
  3. Average intensity of pain more than 3/10 on numerical rating score
  4. Failed trial of appropriate doses of first line medications for neuropathic pain (anticonvulsants and/or antidepressants) for six weeks

Exclusion Criteria:

  1. Age < 18 or Age > 80 years
  2. Perineural or intra-articular steroid injections in the last 6 months
  3. Allergy to local anesthetics or steroids
  4. Ongoing litigation issues related to the patient's pain
  5. Pregnancy
  6. Coagulopathy or systemic infection
  7. Peripheral neuropathy or myopathy, central neuropathic pain (e.g. post-stroke pain)
  8. Infection in the ankle or foot
  9. An unstable medical or psychiatric condition
  10. Significant catastrophizing as indicated by pain catastrophizing scale (PCS) score equal to or more than 30/52.

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: DIAGNOSTIC
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • 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.
ACTIVE_COMPARATOR: Local Anesthetic
Injection of 2-6 cc of LA (0.25% bupivacaine) per nerve to a maximum of 20 cc
Drug: Bupivacaine
Other Names:
  • Marcaine
Drug: Lidocaine
Each injection of study medications will be preceded by subcutaneous injections of 1 mLs of 2% lidocaine at each injection site to reduce discomfort of the study participants from the injections
ACTIVE_COMPARATOR: Local Anesthetic with steroids
Injection of 2-6 cc of LA (0.25% bupivacaine) per nerve containing steroids (methylprednisolone (Depo-Medrol) 4 mg per cc) to a maximum of 20 cc
Drug: Bupivacaine
Other Names:
  • Marcaine
Drug: Lidocaine
Each injection of study medications will be preceded by subcutaneous injections of 1 mLs of 2% lidocaine at each injection site to reduce discomfort of the study participants from the injections
Drug: Depo-Medrol Injectable Product
Other Names:
  • Methylprednisone
PLACEBO_COMPARATOR: Saline
Injection of 2-6 cc of saline (0.9% sodium chloride) per nerve to a maximum of 20 cc
Drug: Lidocaine
Each injection of study medications will be preceded by subcutaneous injections of 1 mLs of 2% lidocaine at each injection site to reduce discomfort of the study participants from the injections
Other: Saline (Sodium Chloride) solution

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
Time Frame
Determination of Numerical Rating Scores (NRS) (range 0-10) for foot and ankle pain
Time Frame: One month after intervention
One month after intervention

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Measuring NRS (range 0-10) for foot and ankle pain
Time Frame: Three months after intervention compared to pre-intervention
Three months after intervention compared to pre-intervention
Measuring changes in the PCS (Pain Catastrophizing Scale) Questionnaire
Time Frame: One month and three months after intervention compared to pre-intervention
One month and three months after intervention compared to pre-intervention
Measuring changes in the Douleur Neuropathique (DN4) Questionnaire
Time Frame: One month and three months after intervention compared to pre-intervention
One month and three months after intervention compared to pre-intervention
Measuring change in the NPSI (Neuropathic Pain Symptom Inventory) Questionnaire
Time Frame: One month and three months after intervention compared to pre-intervention
One month and three months after intervention compared to pre-intervention
Measuring change in the Anxiety and Depression component scores on the Hospital Anxiety and Depression Scale (HADS)
Time Frame: One month and three months after intervention compared to pre-intervention
One month and three months after intervention compared to pre-intervention
Measuring change in Depression scores on the Patient Health Questionnaire (PHQ-9)
Time Frame: One month and three months after intervention compared to pre-intervention
One month and three months after intervention compared to pre-intervention
Measuring change in Brief Pain Inventory interference with activities (BPI-I) score
Time Frame: One month and three months after intervention compared to pre-intervention
One month and three months after intervention compared to pre-intervention
Measuring change in Short Form-12 (SF-12) score
Time Frame: One month and three months after intervention compared to pre-intervention
One month and three months after intervention compared to pre-intervention
Measuring change in Lower Extremity Function Score (LEFS)
Time Frame: One month and three months after intervention compared to pre-intervention
One month and three months after intervention compared to pre-intervention
Measuring change in pain (cold pain and heat pain) thresholds as determined by quantitative sensory testing (QST)
Time Frame: One month and three months after intervention compared to pre-intervention
One month and three months after intervention compared to pre-intervention
Measuring change in sensory (cold and hot detection) thresholds as determined by quantitative sensory testing (QST)
Time Frame: One month and three months after intervention compared to pre-intervention
One month and three months after intervention compared to pre-intervention
Measurement of the cross-sectional area of tibial nerve for neural edema between interventions
Time Frame: One month and three months after intervention compared to pre-intervention
One month and three months after intervention compared to pre-intervention
Measuring incidence of adverse effects
Time Frame: One month and three months after intervention compared to pre-intervention
  1. Hyperglycemia (change in blood glucose levels) and hypertension (change in blood pressure levels)
  2. Infections at the injection site, skin discolouration or atrophy at the injection site, fractures, and evidence of myopathy
One month and three months after intervention compared to pre-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.
University Health Network, Toronto

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

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.
January 1, 2017

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.
March 1, 2018

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.
June 1, 2019

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).
December 28, 2016

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.
December 30, 2016

First Posted (ESTIMATE)

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.
January 4, 2017

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.
March 24, 2020

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.
March 23, 2020

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.
March 1, 2020

More Information

Terms related to this study

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.
  • 16-5927

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

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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