Clinical trial NCT06229964: Frozen Shoulder Treatment with Intra-Articular Corticosteroid Injection and Suprascapular Nerve Block
Official title: A Double Blinded Randomized Controlled Trial (RCT) Exploring the Additional Effect of a Suprascapular Nerve Block in Combination with an Intra-Articular Corticosteroid Injection in Patients with Frozen Shoulder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Frozen Shoulder
Adhesive Capsulitis
Keywords: Frozen Shoulder
Adhesive Capsulitis of the Shoulder
Intra-articular corticosteroid injection
ultra-sound guided injection
suprascapular nerve block
Joint Diseases
Musculoskeletal Diseases
Bursitis
Lead sponsor: Universitair Ziekenhuis Brussel
Sponsor class: OTHER
First posted: 2024-01-29
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective single-center Randomized Parallel-group
Primary purpose: TREATMENT

Brief summary: Frozen shoulder remains a challenging disease to treat as pain and loss of range of motion can persist for many months or even years. This loss of function can have a severe impact on the patient's activities, participation and overall quality of life.

The use of ultrasound-guided (USG) suprascapular nerve blocks (SSNB) and/or intra-articular corticoid injections (IACI) has been supported by many studies. However, double blinded randomized clinical trials using a combination of SSNB and IACI are rare.

The primary objective of this study is to compare the effectiveness of a glenohumeral IACI combined with a SSNB, compared to a glenohumeral IACI combined with a sham SSNB. Outcome measures of interest are shoulder-related disability reported by the patients, shoulder pain and shoulder stiffness. These outcome parameters will be compared between both treatment arms with an intention-to-treat analysis.

As key secondary objectives, the investigators aim to identify which physical examination tests, or combinations of those, are correlated with MRI diagnostic criteria and favor a more positive evolution. Finally, through predictive analysis the investigators will try to establish which patients benefit the most from the combined SSNB + IACI.

Detailed description: Frozen Shoulder (FS) is common disease affecting 2 to 5% of the general population, with a higher prevalence in patients suffering from diabetes and thyroid dysfunction.It remains frustrating for patients and treating health care professionals as severe shoulder pain and loss of function can last for up to two years. 5-7 In the early stage, most patients identify the following symptoms: strong component of night pain, pain with rapid or unguarded movements and aggravated by movement or lying on the affected shoulder.8 Combined with marked pain and limitation in all directions of shoulder range of motion, it is easy to understand that suffering from Frozen Shoulder will have a detrimental effect on quality of life and the ability to perform activities of daily living.

The overall treatment aim for this condition is to "improve pain and function" and treatment goals should be set individually in a shared decision-making process. Patient education on the clinical course and different possible therapeutic interventions, including self-management strategies, should always come first. Clinicians should promote activity modification to utilize pain-free, functional ROM and stretching of the shoulder capsule matching the patient's current level of irritability.

Intra-articular corticosteroid injections (IACI) into the gleno-humeral (GH) joint, combined with shoulder mobility and stretching exercises, have shown to be more effective in providing short-term (4-6weeks) pain relief and improved function compared to exercises alone.

A recent article by Rex et al. places the results of the UK FROST trial in the context of 8 other randomized controlled trials comparing intra-articular corticoid injections (IACI) to manipulation under anesthesia (MUA), arthroscopic capsular release (ACR) and hydrodilatation. These findings did not show clinical superiority of either IACI, MUA nor ACR and evidence for hydrodilatation was inconclusive.

Common sense, in accordance with the National Institute of Health and Care Excellence (NICE) guidelines, recommends that treatments should be offered in a stepped approach from least to most invasive. In their systematic review from 2020, Challoumas et al. show that in the early phase of Frozen Shoulder IA corticosteroid is associated with better short-term outcomes, with possible benefits extending in the mid-terms. These authors recommend to associate IACI to education for home-based exercises and physiotherapy to increase the chances of resolution of symptoms by 6 months.

Unfortunately, not all patients show sufficient improvement in pain and function with IACI and need other therapies. The suprascapular nerve (SSN) provides 60 tot 70% of sensory innervation of the shoulder and suprascapular nerve block (SSNB) has shown in meta-analysis to significantly improve pain and ROM in patients with Frozen Shoulder. This systematic review however has several limitations. Blinding was not always sufficient to rule out a placebo effect, different injections techniques and products (local anesthetics with or without corticosteroids) were used and only data for pain and ROM shoulder could be aggregated as shoulder function was not evaluated in enough trials.

In a rigorous triple blinded RCT, we demonstrated that three successive SSNB with local anesthetics did not improve shoulder pain and function more than three sham injections in patients suffering from subacute Frozen Shoulder. On the other hand, it has been hypothesized that the SSN may be involved in the pathogenesis of Frozen Shoulder and that therefore using optimal approach and drugs (combination of local anesthetics and corticosteroids) in SSNB should be further evaluated in high-quality RCTs.

Evidence suggests that 20mg of triamcinolone or methylprednisolone maybe as effective in frozen shoulder than 40mg but the dosage of 40mg remains most common in clinical and research practice and was chosen to be administered intra-articular in this trial. Trial simulation indicates that the equivalent of 20mg of methylprednisolone is sufficient to increase the mean duration of peripheral nerve blocks and this dosage will be used for SSNB in this study.

In a retrospective review of 102 patients, Jung et al. showed that the combination of an IACI with an SSNB further increased treatment efficacy compared to a single IACI in Frozen Shoulder patients; as pain, ROM and function scored significantly better at different time points (2weeks, 2months and 1 year).

To our knowledge, there has been no previous prospective RCT investigating the added value of an SSNB in combination with an IACI, delivering under ultra-sound guidance the same total amount of corticosteroids in both treatment arms and assuring quadruple blinding (participant, care provider, investigator and outcomes assessor).

The aim of this study is to determine if there is any difference in pain relief and function, as measured by the Shoulder Pain and Disability Index (SPADI), in patients with Frozen Shoulder when given an GH IACI with a SSNB compared to an GH IACI with a sham SSNB. Furthermore, we want to identify which patients will benefit most from GH IACI or the combination of GH IACI and SSNB. The results of this trial will help to guide clinical practice treating patients with FS and improve resource allocation.

Eligibility criteria: Inclusion Criteria:

* Written informed consent to participate in the study must be obtained from the subject prior to initiation of any study-mandated procedure
* Suffering from Frozen Shoulder, defined as: Frozen shoulder is a self-limiting disease characterized by pain and functional restriction in both active and passive shoulder motion lasting more than 1 month, for which radiographic findings of the shoulder joint are unremarkable.
* Dutch or French speaking persons
* Age ≥ 18 years

Exclusion Criteria:

* Subjects with posttraumatic or postsurgical stiff shoulder syndrome
* History of trauma at the onset of symptoms
* Subjects with rheumatologic or neurologic disease involving the shoulder
* Subjects with cervical radiculopathy
* Coagulation disorder
* Hypersensitivity to local anesthetics or MRI contrast agent
* Inability to understand the study procedures
* Psychiatric illness
* Pregnancy
* Subjects who have received prior SSNB in the homolateral shoulder
* Subjects who have received an IACI in the homolateral shoulder in the 3 months before inclusion• Systematic yeast infections
* Hypovolaemia
* Infections at the injection site
* Medical history of malignant hyperthermia, major conduction disorders, acute cardiac decompensation, shock conditions, convulsions

Control subjects for the diagnostic accuracy part of the study protocol

* Inclusion criteria:
* Written informed consent to participate in the study must be obtained from the sub-ject prior to initiation of any study-mandated procedure
* Subjects suffering from shoulder pain that do not fulfill the diagnostic criteria of Frozen Shoulder
* Dutch or French speaking persons
* Age ≥ 18 years
* Contralateral shoulder of Frozen Shoulder subjects
* Exclusion criteria
* Subjects with posttraumatic or postsurgical stiff shoulder syndrome
* History of trauma at the onset of symptoms
* Subjects with rheumatologic or neurologic disease involving the shoulder
* Subjects with cervical radiculopathy
* Coagulation disorder or treatments with anticoagulants
* Hypersensitivity to MRI contrast agent
* Inability to understand the study procedures
* Psychiatric illness
* Pregnancy
* Systematic yeast infections
* Hypovolaemia
* Infections at the injection site
* Medical history of malignant hyperthermia, major conductin disorders, acute cardi-ac decompensation, shock conditions, convulsions

Primary outcomes:
measure: Shoulder Pain and Disability Index (SPADI)
timeFrame: 3 months
Secondary outcomes:
measure: Pain - Numeric Pain Rating Scale (NPRS)
timeFrame: 4 weeks - 3 months - 6 months - 12months after the intervention
measure: Shoulder Pain and Disability Index (SPADI)
timeFrame: 4 weeks- 6 months - 12months after the intervention
measure: Constant- Murley score (CMS)
timeFrame: 4weeks - 3 months - 6 months - 12 months after the intervention
measure: Health related quality of life, evaluated with the EuroQol
timeFrame: 4weeks - 3 months - 6 months - 12 months after the intervention
measure: PROMIS-29 Upper Extremity v2.0
timeFrame: 4weeks - 3 months - 6 months - 12 months after the intervention
measure: Shoulder ROM in abduction, anteflexion, external rotation
timeFrame: 4weeks - 3 months - 6 months - 12 months after the intervention
measure: Tampa Scale for Kinesiophobia (TSK-11):
timeFrame: 4weeks - 3 months - 6 months - 12 months after the intervention
measure: Pain Self-Efficacy Questionnaire (PSEQ)
timeFrame: 4weeks - 3months - 6 months - 12 months after the intervention
measure: Global Rating of Change Score (GRoC)
timeFrame: 4weeks - 3months - 6 months - 12 months after the intervention
measure: Work Ability Index (WAI)
timeFrame: 4weeks - 3months - 6 months - 12 months after the intervention
measure: Work Status
timeFrame: 4weeks - 3months - 6 months - 12 months after the intervention
measure: Health care service use
timeFrame: 4weeks - 3months - 6 months - 12 months after the intervention
measure: Adverse effects
timeFrame: 4weeks - 3months - 6 months - 12 months after the intervention
measure: Rescue therapy
timeFrame: 3months - 6months - 12months after the intervention
Other outcomes:
measure: Superiority analysis of shoulder-related disability, pain and shoulder stiffness at 6 months after start of enrolment.
timeFrame: 6 months after start of enrolment
measure: Exploratory prediction analysis: part 1
timeFrame: 18 months after inclusion
measure: Exploratory prediction analysis: part 2
timeFrame: 18 months after inclusion
measure: Exploratory prediction analysis: part 3
timeFrame: 18 months after inclusion
Locations:
city: Brussels
country: Belgium
facility: Universitair Ziekenhuis Brussel
Study officials:
affiliation: Universitair Ziekenhuis Brussel
name: Marc Schiltz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schiltz M, Goudman L, Moens M, Nijs J, Hatem SM. The diagnostic value of physical examination tests in adhesive capsulitis: a systematic review. Eur J Phys Rehabil Med. 2023 Dec;59(6):724-730. doi: 10.23736/S1973-9087.23.07940-6. Epub 2023 Sep 22.
citation: Jump CM, Waghmare A, Mati W, Malik RA, Charalambous CP. The Impact of Suprascapular Nerve Interventions in Patients with Frozen Shoulder: A Systematic Review and Meta-Analysis. JBJS Rev. 2021 Dec 22;9(12). doi: 10.2106/JBJS.RVW.21.00042.
citation: Kelley MJ, Shaffer MA, Kuhn JE, Michener LA, Seitz AL, Uhl TL, Godges JJ, McClure PW. Shoulder pain and mobility deficits: adhesive capsulitis. J Orthop Sports Phys Ther. 2013 May;43(5):A1-31. doi: 10.2519/jospt.2013.0302. Epub 2013 Apr 30. No abstract available.
citation: Millar NL, Meakins A, Struyf F, Willmore E, Campbell AL, Kirwan PD, Akbar M, Moore L, Ronquillo JC, Murrell GAC, Rodeo SA. Frozen shoulder. Nat Rev Dis Primers. 2022 Sep 8;8(1):59. doi: 10.1038/s41572-022-00386-2.