Randomized Controlled Trial of Efficacy and Safety of Local Anesthetics and Steroids for Chronic Peripheral Post-traumatic Neuropathic Pain
Condition: Neuralgia; Peripheral Neuropathic Pain
MeSH terms: Neuralgia
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Bupivacaine; Depo-Medrol Injectable Product; Saline (Sodium Chloride) solution; Lidocaine
Intervention type(s): Drug; Drug; Other; Drug
Intervention description(s): 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 intervention name(s): Marcaine; Methylprednisone
Intervention MeSH terms: Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Lidocaine; Bupivacaine; Prednisolone hemisuccinate; Prednisolone phosphate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Diagnostic