NeuralgiaPhase 3RESPERISTNCT03009500
Randomized Controlled Trial of Efficacy and Safety of Local Anesthetics and Steroids for Chronic Peripheral Post-traumatic Neuropathic Pain
A Phase 3 study testing Bupivacaine, Depo-Medrol Injectable Product and Saline (Sodium Chloride) solution in people with Neuralgia and Peripheral Neuropathic Pain, run by University Health Network, Toronto at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Neuralgia, Peripheral Neuropathic Pain
- What is being tested?
- Bupivacaine, Depo-Medrol Injectable Product and Saline (Sodium Chloride) solution
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3 participants
- Where
- 1 siteCanada
- Study dates
- Jan 2017to Jun 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pain in foot in neuro-anatomically congruent location following trauma (including surgery) for more than three months
- Physician-reported DN4 scoring confirming neuropathic pain (score >3/10)
- Average intensity of pain more than 3/10 on numerical rating score
- Failed trial of appropriate doses of first line medications for neuropathic pain (anticonvulsants and/or antidepressants) for six weeks
Who cannot join
- Age < 18 or Age > 80 years
- Perineural or intra-articular steroid injections in the last 6 months
- Allergy to local anesthetics or steroids
- Ongoing litigation issues related to the patient's pain
- Pregnancy
- Coagulopathy or systemic infection
Show all 10Show fewer
- Peripheral neuropathy or myopathy, central neuropathic pain (e.g. post-stroke pain)
- Infection in the ankle or foot
- An unstable medical or psychiatric condition
- Significant catastrophizing as indicated by pain catastrophizing scale (PCS) score equal to or more than 30/52.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Neuralgia, Peripheral Neuropathic Pain
- Being tested
- Bupivacaine, Depo-Medrol Injectable Product, Saline (Sodium Chloride) solution, Lidocaine
- Medical subject headings
- Neuralgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BupivacaineDrug
Also called Marcaine
Depo-Medrol Injectable ProductDrug
Also called Methylprednisone
Saline (Sodium Chloride) solutionOther
LidocaineDrug
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 group | Role | What they receive |
|---|---|---|
| Local Anesthetic | Active comparator | Injection of 2-6 cc of LA (0.25% bupivacaine) per nerve to a maximum of 20 cc Receives: Drug: Bupivacaine; Drug: Lidocaine |
| Local Anesthetic with steroids | Active comparator | 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 Receives: Drug: Bupivacaine; Drug: Depo-Medrol Injectable Product; Drug: Lidocaine |
| Saline | Placebo comparator | Injection of 2-6 cc of saline (0.9% sodium chloride) per nerve to a maximum of 20 cc Receives: Other: Saline (Sodium Chloride) solution; Drug: Lidocaine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of Numerical Rating Scores (NRS) (range 0-10) for foot and ankle pain
Measured: One month after intervention
Secondary outcomes (13)
Measuring NRS (range 0-10) for foot and ankle pain
Measured: Three months after intervention compared to pre-intervention
Measuring changes in the PCS (Pain Catastrophizing Scale) Questionnaire
Measured: One month and three months after intervention compared to pre-intervention
Measuring changes in the Douleur Neuropathique (DN4) Questionnaire
Measured: One month and three months after intervention compared to pre-intervention
Measuring change in the NPSI (Neuropathic Pain Symptom Inventory) Questionnaire
Measured: 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)
Measured: One month and three months after intervention compared to pre-intervention
Measuring change in Depression scores on the Patient Health Questionnaire (PHQ-9)
Measured: One month and three months after intervention compared to pre-intervention
Measuring change in Brief Pain Inventory interference with activities (BPI-I) score
Measured: One month and three months after intervention compared to pre-intervention
Measuring change in Short Form-12 (SF-12) score
Measured: One month and three months after intervention compared to pre-intervention
Measuring change in Lower Extremity Function Score (LEFS)
Measured: 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)
Measured: 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)
Measured: 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
Measured: One month and three months after intervention compared to pre-intervention
Measuring incidence of adverse effects
- Hyperglycemia (change in blood glucose levels) and hypertension (change in blood pressure levels)
- Infections at the injection site, skin discolouration or atrophy at the injection site, fractures, and evidence of myopathy
Measured: One month and three months after intervention compared to pre-intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2017 (estimated)
- Study startJan 2017
- Primary completionMar 2018
- Study completionJun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeuralgiaStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Anuj Bhatia, University Health Network, Toronto
- Investigators
- Anuj Bhatia, MD FRCPC, Principal investigator, UHN
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03009500
- Sponsor's protocol ID
- 16-5927
- Acronym
- RESPERIST
- Status last verified
- Mar 2020
- First submitted
- 28 Dec 2016
- Last updated
- 24 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03009500
- Acronym / sponsor ID
- RESPERIST / 16-5927
- Conditions
- Neuralgia, Peripheral Neuropathic Pain
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- Jan 2017
- Primary completion
- Mar 2018 (actual)
- Study completion
- Jun 2019 (actual)
- First posted
- 4 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Local Anesthetic | Active comparator | Drug: Bupivacaine, Drug: LidocaineInjection of 2-6 cc of LA (0.25% bupivacaine) per nerve to a maximum of 20 cc |
| Local Anesthetic with steroids | Active comparator | Drug: Bupivacaine, Drug: Depo-Medrol Injectable Product, Drug: LidocaineInjection 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 |
| Saline | Placebo comparator | Other: Saline (Sodium Chloride) solution, Drug: LidocaineInjection of 2-6 cc of saline (0.9% sodium chloride) per nerve to a maximum of 20 cc |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Pain in foot in neuro-anatomically congruent location following trauma (including surgery) for more than three months
- Physician-reported DN4 scoring confirming neuropathic pain (score >3/10)
- Average intensity of pain more than 3/10 on numerical rating score
- Failed trial of appropriate doses of first line medications for neuropathic pain (anticonvulsants and/or antidepressants) for six weeks
Key exclusion criteria (10 listed)
- Age < 18 or Age > 80 years
- Perineural or intra-articular steroid injections in the last 6 months
- Allergy to local anesthetics or steroids
- Ongoing litigation issues related to the patient's pain
- Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BupivacaineAlso: Marcaine | Drug | Local Anesthetic, Local Anesthetic with steroids |
| Depo-Medrol Injectable ProductAlso: Methylprednisone | Drug | Local Anesthetic with steroids |
| Saline (Sodium Chloride) solution | Other | Saline |
| LidocaineEach 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 | Local Anesthetic, Local Anesthetic with steroids, Saline |
Primary outcome
Determination of Numerical Rating Scores (NRS) (range 0-10) for foot and ankle pain
Time frame: One month after intervention
13 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anuj Bhatia, MD FRCPC principal investigator
UHN
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Bupivacaine, Depo-Medrol Injectable Product and Saline (Sodium Chloride) solution in people with Neuralgia and Peripheral Neuropathic Pain, run by University Health Network, Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determination of Numerical Rating Scores (NRS) (range 0-10) for foot and ankle pain (time frame: One month after intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2020.