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

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ClinicalTrials.gov Identifier: NCT03009500
Recruitment Status : Recruiting
First Posted : January 4, 2017
Last Update Posted : October 11, 2018
Sponsor:
Information provided by (Responsible Party):
Anuj Bhatia, University Health Network, Toronto

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Neuralgia Peripheral Neuropathic Pain Drug: Bupivacaine Drug: Depo-Medrol Injectable Product Other: Saline (Sodium Chloride) solution Drug: Lidocaine Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Diagnostic
Official Title: 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
Study Start Date : January 2017
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : June 2019

Arm Intervention/treatment
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 Name: 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 Name: Marcaine

Drug: Depo-Medrol Injectable Product
Other Name: Methylprednisone

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

Placebo Comparator: Saline
Injection of 2-6 cc of saline (0.9% sodium chloride) per nerve to a maximum of 20 cc
Other: Saline (Sodium Chloride) solution
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




Primary Outcome Measures :
  1. Determination of Numerical Rating Scores (NRS) (range 0-10) for foot and ankle pain [ Time Frame: One month after intervention ]

Secondary Outcome Measures :
  1. Measuring NRS (range 0-10) for foot and ankle pain [ Time Frame: Three months after intervention compared to pre-intervention ]
  2. Measuring changes in the PCS (Pain Catastrophizing Scale) Questionnaire [ Time Frame: One month and three months after intervention compared to pre-intervention ]
  3. Measuring changes in the Douleur Neuropathique (DN4) Questionnaire [ Time Frame: One month and three months after intervention compared to pre-intervention ]
  4. Measuring change in the NPSI (Neuropathic Pain Symptom Inventory) Questionnaire [ Time Frame: One month and three months after intervention compared to pre-intervention ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. Measuring change in Short Form-12 (SF-12) score [ Time Frame: One month and three months after intervention compared to pre-intervention ]
  9. Measuring change in Lower Extremity Function Score (LEFS) [ Time Frame: One month and three months after intervention compared to pre-intervention ]
  10. 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 ]
  11. 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 ]
  12. 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 ]
  13. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03009500


Contacts
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Contact: Anuj Bhatia, MD FRCPC (416) 603 5800 ext 6136 anuj.bhatia@uhn.ca

Locations
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Canada, Ontario
Toronto Western Hospital Recruiting
Toronto, Ontario, Canada, M5T 2S8
Contact: Anuj Bhatia, MD FRCPC    (416) 603 5800 ext 6136    anuj.bhatia@uhn.ca   
Contact: Jamal Kara    (416) 603 5800 ext 6237    jamal.kara@uhn.ca   
Sponsors and Collaborators
University Health Network, Toronto
Investigators
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Principal Investigator: Anuj Bhatia, MD FRCPC UHN

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Responsible Party: Anuj Bhatia, Director, Anesthesia Chronic Pain Clinical Services, University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT03009500     History of Changes
Other Study ID Numbers: 16-5927
First Posted: January 4, 2017    Key Record Dates
Last Update Posted: October 11, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Neuromuscular Diseases
Lidocaine
Neuralgia
Peripheral Nervous System Diseases
Nervous System Diseases
Pain
Neurologic Manifestations
Signs and Symptoms
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Bupivacaine
Anesthetics, Local
Anesthetics
Prednisolone hemisuccinate
Prednisolone phosphate
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Anti-Arrhythmia Agents
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents