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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

Tracking Information
First Submitted Date  ICMJE December 28, 2016
First Posted Date  ICMJE January 4, 2017
Last Update Posted Date October 11, 2018
Study Start Date  ICMJE January 2017
Estimated Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 30, 2016)
Determination of Numerical Rating Scores (NRS) (range 0-10) for foot and ankle pain [ Time Frame: One month after intervention ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03009500 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 30, 2016)
  • Measuring NRS (range 0-10) for foot and ankle pain [ Time Frame: 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 ]
  • Measuring changes in the Douleur Neuropathique (DN4) Questionnaire [ Time Frame: 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • Measuring change in Short Form-12 (SF-12) score [ Time Frame: 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Randomized Controlled Trial of Efficacy and Safety of Local Anesthetics and Steroids for Chronic Peripheral Post-traumatic Neuropathic Pain
Official Title  ICMJE 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
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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Diagnostic
Condition  ICMJE
  • Neuralgia
  • Peripheral Neuropathic Pain
Intervention  ICMJE
  • Drug: Bupivacaine
    Other Name: Marcaine
  • Drug: Depo-Medrol Injectable Product
    Other Name: Methylprednisone
  • 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
Study Arms  ICMJE
  • Active Comparator: Local Anesthetic
    Injection of 2-6 cc of LA (0.25% bupivacaine) per nerve to a maximum of 20 cc
    Interventions:
    • Drug: Bupivacaine
    • Drug: Lidocaine
  • 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
    Interventions:
    • Drug: Bupivacaine
    • Drug: Depo-Medrol Injectable Product
    • Drug: Lidocaine
  • Placebo Comparator: Saline
    Injection of 2-6 cc of saline (0.9% sodium chloride) per nerve to a maximum of 20 cc
    Interventions:
    • Other: Saline (Sodium Chloride) solution
    • Drug: Lidocaine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 30, 2016)
90
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2019
Estimated Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Anuj Bhatia, MD FRCPC (416) 603 5800 ext 6136 anuj.bhatia@uhn.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03009500
Other Study ID Numbers  ICMJE 16-5927
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Anuj Bhatia, University Health Network, Toronto
Study Sponsor  ICMJE University Health Network, Toronto
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Anuj Bhatia, MD FRCPC UHN
PRS Account University Health Network, Toronto
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP