Peripheral Nerve Injections for CRPS

Study Overview
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Brief Summary
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Background Complex regional pain syndrome (CRPS) is characterized by intense pain and loss of function, and associated with motor, trophic, sudomotor, and/or vasomotor changes of the affected extremity. CRPS of the upper extremity is seen frequently in our electrodiagnostic, neurology, and musculoskeletal clinics and occurs in up to one-third of patients who have undergone common surgical procedures, such as carpal tunnel release or release of Dupuytren's contracture. To date, there is a limited understanding of the underlying pathophysiology of CRPS. As a consequence, few effective treatment options are available. Peripheral nerve blocks have proven to be successful in reducing pain for several musculoskeletal and neurologic conditions. These blocks could be an opportunity for blocking somatic and autonomic sensory fibers that are thought to contribute to CRPS. In a small exploratory study, we found that peripheral nerve blocks in the upper extremity (suprascapular and median nerves) resulted in a 56% and 37% pain reduction in the shoulder and hand two weeks after injection, respectively, and were well-tolerated in patients with CRPS. While this was highly encouraging, large randomized placebo-controlled trials (RCTs) are necessary to demonstrate effectiveness and safety of nerve blocks for this population before this treatment is accepted into clinical practice. This proposal aims to demonstrate the feasibility of performing such a RCT. Objective To evaluate the feasibility of performing a placebo-controlled RCT assessing the efficacy and safety of peripheral nerve blocks (suprascapular, median, and ulnar nerves) for reducing pain in patients with CRPS. This is a phase IV feasibility study that will test the critical elements necessary for performing a RCT. Methods We will recruit participants (≥18 years old) from The Ottawa Hospital, Bruyère Continuing Care (Elisabeth Bruyère Hospital, St-Vincent Hospital), and Providence Care Hospital (Kingston, ON), meeting the well-established clinical Budapest criteria for upper extremity CRPS and having a visual analog scale (VAS) pain score of at least 40 mm (to avoid flooring effect). Participants will be block-randomized by the Ottawa Methods Centre to receive injections of either A) intervention (suprascapular, median, and ulnar nerves) with bupivacaine and triamcinolone acetonide, or B) placebo (saline). All participants will receive standard care for CRPS. Feasibility outcomes will focus on crucial methodologic aspects for the future RCT, including: (1) level of recruitment, (2) rate of acceptance from eligible patients to the randomization procedure, (3) blinding efficacy, (4) degree of patient retention, (5) rate of data completion, and (6) rate of adverse events for both the placebo and intervention groups. Outcome measures will be evaluated within 1 hour, 2 weeks, 6 weeks, and 3 months post-injection.

Official Title
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Peripheral Nerve Injections for the Treatment of Upper Extremity Complex Regional Pain Syndrome: A Feasibility Study for a Proposed Randomized Design

Conditions
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Complex Regional Pain Syndromes

Intervention / Treatment
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* Drug: Triamcinolone Acetonide 40mg/mL
* Drug: Saline Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to provide signed and dated informed consent form Male or female, aged ≥18 years old Satisfy the Budapest Criteria for upper extremity CRPS A VAS score of at least 40 mm in the upper extremity to avoid flooring effect for injection-related pain reduction Exclusion Criteria: Uncontrolled hypertension (>180/110) Sepsis Bleeding diathesis Active cancer Brachial plexus injuries Neurological language deficits precluding participation Mini mental state examination score < 23 Acute mental illness (An acute mental illness is characterized by clinically significant symptoms of any metal health illness that requires immediate treatment. The physician making the recommendation to be part of the study. If the patient exhibits symptoms of any mental health illness that is not being treated by either the recommending physician or another member of the patient's care team the patient will not be recommended to participate in the study) Patients who are pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>The intervention group will receive: Suprascapular nerve block - 3 mL of 0.5% Bupivacaine and 1 mL of 40 mg/mL Kenalog Median nerve block - 3.5 mL of 0.5% Bupivacaine and 0.5 mL of 40 mg/mL Kenalog Ulnar nerve block - 3.5 mL of 0.5% Bupivacaine and 0.5 mL of 40 mg/mL Kenalog | Drug: Triamcinolone Acetonide 40mg/mL<br>* Triamcinolone acetonide is a synthetic glucocorticoid corticosteroid with marked anti-inflammatory action, in a sterile aqueous suspension suitable for intramuscular, intra-articular, and intrabursal injection.<br>* Other names: Kenalog;|
| Placebo Comparator: Placebo<br>Placebo The placebo group will receive: Suprascapular nerve injection - 4 mL of normal saline Median nerve injection - 4 mL of normal saline Ulnar nerve injection - 4 mL of normal saline | Drug: Saline Injection<br>* Saline is a buffer solution commonly used in biological research. It is a water-based salt solution containing disodium hydrogen phosphate, sodium chloride and, in some formulations, potassium chloride and potassium dihydrogen phosphate. The buffer helps to maintain a constant pH. The osmolarity and ion concentrations of the solutions match those of the human body.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment | Number of participants who are successfully recruit into the study. | Week -2 | 
| Randomization | Number of participants who accept being randomized into either the intervention or placebo treatment arms and receive the injection accordingly. | Week 0 | 
| Blinding - Participant | The participants will be asked which arm they believe they are part of and this response will be compared to their actual group allocation. The level of agreement between the actual group allocation and the guess provided will be compared using Bang's blinding index, we will consider blinding effective if the index is between -0.2 and 0.2 (zero being perfect blinding). | Week 0 | 
| Blinding - Participant | The participants will be asked which arm they believe they are part of and this response will be compared to their actual group allocation. The level of agreement between the actual group allocation and the guess provided will be compared using Bang's blinding index, we will consider blinding effective if the index is between -0.2 and 0.2 (zero being perfect blinding). | Week 2 | 
| Blinding - Participant | The participants will be asked which arm they believe they are part of and this response will be compared to their actual group allocation. The level of agreement between the actual group allocation and the guess provided will be compared using Bang's blinding index, we will consider blinding effective if the index is between -0.2 and 0.2 (zero being perfect blinding). | Week 6 | 
| Blinding - Participant | The participants will be asked which arm they believe they are part of and this response will be compared to their actual group allocation. The level of agreement between the actual group allocation and the guess provided will be compared using Bang's blinding index, we will consider blinding effective if the index is between -0.2 and 0.2 (zero being perfect blinding). | Week 12 | 
| Blinding - Interventionist | The interventionist will be asked which arm they believe the participant is are part of and this response will be compared to their actual group allocation. The level of agreement between the actual group allocation and the guess provided will be compared using Bang's blinding index, we will consider blinding effective if the index is between -0.2 and 0.2 (zero being perfect blinding). | Week 0 | 
| Blinding - Physiotherapist | The physiotherapist will be asked which arm they believe the participant is are part of and this response will be compared to their actual group allocation. The level of agreement between the actual group allocation and the guess provided will be compared using Bang's blinding index, we will consider blinding effective if the index is between -0.2 and 0.2 (zero being perfect blinding). | Week 2 | 
| Blinding - Physiotherapist | The physiotherapist will be asked which arm they believe the participant is are part of and this response will be compared to their actual group allocation. The level of agreement between the actual group allocation and the guess provided will be compared using Bang's blinding index, we will consider blinding effective if the index is between -0.2 and 0.2 (zero being perfect blinding). | Week 6 | 
| Blinding - Physiotherapist | The physiotherapist will be asked which arm they believe the participant is are part of and this response will be compared to their actual group allocation. The level of agreement between the actual group allocation and the guess provided will be compared using Bang's blinding index, we will consider blinding effective if the index is between -0.2 and 0.2 (zero being perfect blinding). | Week 12 | 
| Retention | The percentage of participants who remained in the study for the entire duration of their planned involvement. | Week 12 | 
| Data completion | The percentage of participants who complete all of the study questionnaires | Week 12 | 
| Rate of Adverse events | We will track adverse events the participants experience | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain - Visual Analog Scale | We will track the pain experienced by the participants on a visual analog scale. The lowest score is 0 the highest score is 10. A higher value indicates a higher amount of pain experienced by the participant | Week -2 | 
| Pain - Visual Analog Scale | We will track the pain experienced by the participants on a visual analog scale. The lowest score is 0 the highest score is 10. A higher value indicates a higher amount of pain experienced by the participant | Week 0 - Immediately before injection | 
| Pain - Visual Analog Scale | We will track the pain experienced by the participants on a visual analog scale. The lowest score is 0 the highest score is 10. A higher value indicates a higher amount of pain experienced by the participant | Week 0 - Immediately after injection | 
| Pain - Visual Analog Scale | We will track the pain experienced by the participants on a visual analog scale. The lowest score is 0 the highest score is 10. A higher value indicates a higher amount of pain experienced by the participant | Week 2 | 
| Pain - Visual Analog Scale | We will track the pain experienced by the participants on a visual analog scale. The lowest score is 0 the highest score is 10. A higher value indicates a higher amount of pain experienced by the participant | Week 6 | 
| Pain - Visual Analog Scale | We will track the pain experienced by the participants on a visual analog scale. The lowest score is 0 the highest score is 10. A higher value indicates a higher amount of pain experienced by the participant | Week 12 | 
| Pain - Patient-Reported Outcomes Measurement Information System 29 Profile V2 | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 4 and the highest possible score is 30, and a higher score indicates a worse outcome. | Week -2 | 
| Pain - Patient-Reported Outcomes Measurement Information System 29 Profile V2 | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 4 and the highest possible score is 30, and a higher score indicates a worse outcome. | Week 0 | 
| Pain - Patient-Reported Outcomes Measurement Information System 29 Profile V2 | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 4 and the highest possible score is 30, and a higher score indicates a worse outcome. | Week 2 | 
| Pain - Patient-Reported Outcomes Measurement Information System 29 Profile V2 | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 4 and the highest possible score is 30, and a higher score indicates a worse outcome. | Week 6 | 
| Pain - Patient-Reported Outcomes Measurement Information System 29 Profile V2 | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 4 and the highest possible score is 30, and a higher score indicates a worse outcome. | Week 12 | 
| Pain - EQ-5D-5L | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 1 and the highest possible score is 5, and a higher score indicates a worse outcome. | Week -2 | 
| Pain - EQ-5D-5L | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 1 and the highest possible score is 5, and a higher score indicates a worse outcome. | Week 0 | 
| Pain - EQ-5D-5L | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 1 and the highest possible score is 5, and a higher score indicates a worse outcome. | Week 2 | 
| Pain - EQ-5D-5L | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 1 and the highest possible score is 5, and a higher score indicates a worse outcome. | Week 6 | 
| Pain - EQ-5D-5L | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 1 and the highest possible score is 5, and a higher score indicates a worse outcome. | Week 12 | 
| Disease Severity - Complex Regional Pain Syndrome Severity Score | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 0 and the highest possible score is 17, and a higher score indicates a worse outcome. | Week -2 | 
| Disease Severity - Complex Regional Pain Syndrome Severity Score | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 0 and the highest possible score is 17, and a higher score indicates a worse outcome. | Week 0 | 
| Disease Severity - Complex Regional Pain Syndrome Severity Score | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 0 and the highest possible score is 17, and a higher score indicates a worse outcome. | Week 2 | 
| Disease Severity - Complex Regional Pain Syndrome Severity Score | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 0 and the highest possible score is 17, and a higher score indicates a worse outcome. | Week 6 | 
| Disease Severity - Complex Regional Pain Syndrome Severity Score | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 0 and the highest possible score is 17, and a higher score indicates a worse outcome. | Week 12 | 
| Function - Disabilities of the Arm, Shoulder, and Hand Questionnaire | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 0 and the highest possible score is 100, and a higher score indicates a worse outcome. | Week -2 | 
| Function - Disabilities of the Arm, Shoulder, and Hand Questionnaire | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 0 and the highest possible score is 100, and a higher score indicates a worse outcome. | Week 0 | 
| Function - Disabilities of the Arm, Shoulder, and Hand Questionnaire | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 0 and the highest possible score is 100, and a higher score indicates a worse outcome. | Week 2 | 
| Function - Disabilities of the Arm, Shoulder, and Hand Questionnaire | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 0 and the highest possible score is 100, and a higher score indicates a worse outcome. | Week 6 | 
| Function - Disabilities of the Arm, Shoulder, and Hand Questionnaire | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 0 and the highest possible score is 100, and a higher score indicates a worse outcome. | Week 12 | 
| Function - Patient-Reported Outcomes Measurement Information System 29 Profile V2 | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 8 and the highest possible score is 40, and a higher score indicates a better outcome. | Week -2 | 
| Function - Patient-Reported Outcomes Measurement Information System 29 Profile V2 | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 8 and the highest possible score is 40, and a higher score indicates a better outcome. | Week 0 | 
| Function - Patient-Reported Outcomes Measurement Information System 29 Profile V2 | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 8 and the highest possible score is 40, and a higher score indicates a better outcome. | Week 2 | 
| Function - Patient-Reported Outcomes Measurement Information System 29 Profile V2 | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 8 and the highest possible score is 40, and a higher score indicates a better outcome. | Week 6 | 
| Function - Patient-Reported Outcomes Measurement Information System 29 Profile V2 | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 8 and the highest possible score is 40, and a higher score indicates a better outcome. | Week 12 | 
| Emotional and Psychological Function - Patient-Reported Outcomes Measurement Information System 29 Profile V2 | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 16 and the highest possible score is 80, and a higher score indicates a worse outcome. | Week -2 | 
| Emotional and Psychological Function - Patient-Reported Outcomes Measurement Information System 29 Profile V2 | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 16 and the highest possible score is 80, and a higher score indicates a worse outcome. | Week 0 | 
| Emotional and Psychological Function - Patient-Reported Outcomes Measurement Information System 29 Profile V2 | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 16 and the highest possible score is 80, and a higher score indicates a worse outcome. | Week 2 | 
| Emotional and Psychological Function - Patient-Reported Outcomes Measurement Information System 29 Profile V2 | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 16 and the highest possible score is 80, and a higher score indicates a worse outcome. | Week 6 | 
| Emotional and Psychological Function - Patient-Reported Outcomes Measurement Information System 29 Profile V2 | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 16 and the highest possible score is 80, and a higher score indicates a worse outcome. | Week 12 | 
| Emotional and Psychological Function - EQ-5D-5L | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 1 and the highest possible score is 5, and a higher score indicates a worse outcome. | Week -2 | 
| Emotional and Psychological Function - EQ-5D-5L | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 1 and the highest possible score is 5, and a higher score indicates a worse outcome. | Week 0 | 
| Emotional and Psychological Function - EQ-5D-5L | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 1 and the highest possible score is 5, and a higher score indicates a worse outcome. | Week 2 | 
| Emotional and Psychological Function - EQ-5D-5L | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 1 and the highest possible score is 5, and a higher score indicates a worse outcome. | Week 6 | 
| Emotional and Psychological Function - EQ-5D-5L | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 1 and the highest possible score is 5, and a higher score indicates a worse outcome. | Week 12 | 
| Quality of Life - EQ-5D-5L | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 1 and the highest possible score is 5, and a higher score indicates a worse outcome. | Week -2 | 
| Quality of Life - EQ-5D-5L | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 1 and the highest possible score is 5, and a higher score indicates a worse outcome. | Week 0 | 
| Quality of Life - EQ-5D-5L | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 1 and the highest possible score is 5, and a higher score indicates a worse outcome. | Week 2 | 
| Quality of Life - EQ-5D-5L | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 1 and the highest possible score is 5, and a higher score indicates a worse outcome. | Week 6 | 
| Quality of Life - EQ-5D-5L | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 1 and the highest possible score is 5, and a higher score indicates a worse outcome. | Week 12 | 
| Total Score - EQ-5D-5L | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 5 and the highest possible score is 25, and a higher score indicates a worse outcome. | Week -2 | 
| Total Score - EQ-5D-5L | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 5 and the highest possible score is 25, and a higher score indicates a worse outcome. | Week 0 | 
| Total Score - EQ-5D-5L | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 5 and the highest possible score is 25, and a higher score indicates a worse outcome. | Week 2 | 
| Total Score - EQ-5D-5L | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 5 and the highest possible score is 25, and a higher score indicates a worse outcome. | Week 6 | 
| Total Score - EQ-5D-5L | These outcomes will allow us to better understand the holistic effect of the intervention. The lowest possible score is 5 and the highest possible score is 25, and a higher score indicates a worse outcome. | Week 12 |