Peripheral Nerve Injections for CRPS

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

Background Complex regional pain syndrome (CRPS) is characterized by intense pain, loss of function, and associated with motor, trophic, sudomotor, and/or vasomotor changes of the affected extremity. Upper extremity CRPS is seen frequently in electrodiagnostic, neurology, and musculoskeletal clinics and occurs in up to one-third of patients who have undergone common surgical procedures (i.e. carpal tunnel surgery). 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. Similarly, this procedure could be used to block somatic and autonomic sensory fibers which are thought to contribute to CRPS. In a small exploratory study, investigators found peripheral nerve blocks in the upper extremity (suprascapular and median nerves) were well-tolerated in patients with CRPS and resulted in a 56% and 37% pain reduction in the shoulder and hand 2 weeks after injection, respectively. While this is highly encouraging, large randomized placebo-controlled trials (RCTs) are necessary to demonstrate effectiveness and safety of nerve blocks for this population before it is accepted into clinical practice. This proposal is a phase II feasibility study that will test the critical elements necessary for performing such a RCT.

Methods The investigators 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.

Primary 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Complex Regional Pain Syndromes
• Intervention / Treatment: Drug: Triamcinolone Acetonide 40mg/mL; Drug: Saline Injection; Drug: Bupivacaine

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital
    • Ottawa, Ontario, Canada, K1N5C8
      • Elisabeth Bruyere Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Able to provide signed and dated informed consent form
2. Male or female, aged ≥18 years old
3. Satisfy the Budapest Criteria for upper extremity CRPS
4. A VAS score of at least 40 mm in the upper extremity to avoid flooring effect for injection-related pain reduction

Exclusion Criteria:

1. Uncontrolled hypertension (>180/110)
2. Sepsis
3. Bleeding diathesis
4. Active cancer
5. Brachial plexus injuries
6. Neurological language deficits precluding participation
7. Mini mental state examination score < 23
8. 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)
9. Patients who are pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; 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; 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.; Other Names: Kenalog; Drug: Bupivacaine; Bupivacaine is an anesthetic that is commonly used as a local numbing agent, including intramuscular, intra-articular and intrabursal injections.; Other Names: Marcaine
Placebo Comparator: Placebo; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Investigators: Principal Investigator: Mark Campbell, MD, Elisabeth Bruyere Hospital and The Ottawa Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2024
• Primary Completion (Actual): July 30, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: January 21, 2021
• First Submitted That Met QC Criteria: February 3, 2021
• First Posted (Actual): February 9, 2021

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 16, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Disease; Neuromuscular Diseases; Peripheral Nervous System Diseases; Autonomic Nervous System Diseases; Syndrome; Complex Regional Pain Syndromes; Reflex Sympathetic Dystrophy; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Sensory System Agents; Anesthetics; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anesthetics, Local; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate; Bupivacaine
• Other Study ID Numbers: 20200600-01H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No