Evaluation of Intra-Articular Corticosteroid Injection and Suprascapular Nerve Block in Patients with Adhesive Capsulitis Using Methylprednisolone Acetate and Ropivacaine Hydrochloride

The primary objective of this study is to evaluate the efficacy of a **Gleno-Humeral (GH) intra-articular corticosteroid injection (IACI)** combined with a suprascapular nerve block (SSNB) compared to a GH IACI with a sham SSNB in providing pain relief and improving function in patients with **Frozen Shoulder**. The clinical relevance of this objective lies in its potential to enhance treatment protocols for Frozen Shoulder, thereby improving patient outcomes and optimizing resource allocation. The key primary endpoint is the change in shoulder-related disability three months post-intervention, assessed using the Shoulder Pain and Disability Index (SPADI).

The secondary objectives include:

• Conducting an intermediary statistical analysis at six months to determine the necessity of extending the study to twelve months based on outcomes such as disability, pain, and shoulder stiffness.
• Evaluating secondary outcomes including NPRS, SPADI at 6-12 months, Constant-Murley Score, EQ-5D-3L, PROMIS-29 Upper Extremity v2.0 Physical Function, Shoulder ROM, Frozen Shoulder Clinical Tests, Shoulder Impingement Tests, Tampa Scale for Kinesiophobia, Pain Self-Efficacy Questionnaire, Global Rating of Change Score, Work Ability Index, work status, healthcare service use, adverse effects, and use of rescue therapy.
• Performing linear regression analysis to identify clinical examination tests and/or MRI criteria with the best diagnostic accuracy in early-phase Frozen Shoulder.
• Conducting exploratory prediction analysis to identify physical examination tests correlated with MRI diagnostic criteria and positive evolution of SPADI, NPR pain, shoulder ROM, and return to work/work ability index, as well as determining which patients benefit most from the combined SSNB + IACI.

The clinical trial involves participants diagnosed with **Frozen Shoulder**, also known as **Adhesive Capsulitis**. The study population includes both male and female subjects aged 18 years and older. Participants are required to be either Dutch or French speaking. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Selection criteria include individuals experiencing shoulder pain with functional restriction in both active and passive shoulder motion for more than one month, with unremarkable radiographic findings. Control subjects include those with shoulder pain not meeting the diagnostic criteria for Frozen Shoulder and the contralateral shoulder of affected individuals. Participants' general health status, lifestyle considerations such as diet, physical activity, or habits, are not specified by the sponsor.

The clinical trial is designed to evaluate the efficacy of **intra-articular corticosteroid injection** (IACI) combined with a **suprascapular nerve block** (SSNB) in patients diagnosed with **Frozen Shoulder**, also known as **Adhesive Capsulitis**. This study employs a **randomized, double-blind, controlled** methodology to ensure the reliability and validity of the results. The trial is expected to span from September 2024 to December 2026, with participant involvement lasting up to 12 months, depending on the outcomes of intermediary analyses.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, language proficiency, and specific diagnostic criteria for Frozen Shoulder. Following randomization, participants will receive either the active treatment or a sham procedure. Follow-up visits are scheduled at 4 weeks, 3 months, 6 months, and 12 months post-intervention to assess primary and secondary endpoints, including changes in shoulder-related disability, pain levels, and range of motion. The primary endpoint is the change in shoulder-related disability at 3 months, measured by the Shoulder Pain and Disability Index (SPADI).

Participants may be withdrawn from the study if they experience adverse effects, require rescue therapy, or if intermediary statistical analyses at 6 months indicate non-superiority of the treatment outcomes. The study aims to identify which patients benefit most from the treatment, thereby optimizing clinical practice and resource allocation for managing Frozen Shoulder. The trial's design and procedures are structured to maintain scientific rigor while ensuring participant safety and data integrity.

The clinical trial involves the administration of several treatments, including **Ropivacaine Hydrochloride**, marketed as Ropivacaïne Fresenius Kabi 2 mg/ml oplossing voor injectie. This medication is provided in the form of a **solution for injection** and is administered via **infiltration**. The maximum daily and total dose is 675 mg, with a treatment period limited to one day. The active substance, ropivacaine hydrochloride, is of chemical origin and is utilized for its local anesthetic properties, classified under the ATC code N01BB09.

Another treatment used in the trial is **Methylprednisolone Acetate**, available as Depo-Medrol 40 mg/1 ml Injektionssuspension and Depo-Medrol 40 mg/1 ml Suspension Injectable. Both formulations are **suspensions for injection** and are administered through **infiltration**. The maximum daily and total dose for the Injektionssuspension is 675 mg, while the Suspension Injectable has a maximum daily and total dose of 80 mg. The treatment period for both is restricted to one day. Methylprednisolone acetate is a corticosteroid with anti-inflammatory properties, classified under the ATC code H02AB04.

The trial also includes the use of **Lidocaine Hydrochloride Monohydrate**, marketed as Linisol 2% oplossing voor injectie. This medication is a **solution for injection** and is administered via **injection**. The maximum daily and total dose is 10 ml, with a treatment period of one day. Lidocaine hydrochloride monohydrate is a local anesthetic, classified under the ATC codes C01BB01 and N01BB02, and is used for its numbing effects.

All substances used in the trial are of chemical origin, and participant compliance with dosing schedules is monitored to ensure adherence to the treatment protocol. The trial aims to evaluate the efficacy of these treatments in managing pain and improving function in patients with Frozen Shoulder, with a focus on comparing the effects of different combinations of treatments.

Efficacy in the clinical trial for the treatment of **Frozen Shoulder** will be assessed using both primary and secondary endpoints. The primary endpoint is the change in shoulder-related disability, evaluated 3 months post-intervention compared to the control group. This will be measured using the validated Shoulder Pain and Disability Index (SPADI) questionnaire.

Secondary endpoints include a variety of assessments conducted at multiple time points: 4 weeks, 3 months, 6 months, and 12 months after the intervention. These assessments will utilize several tools and scales, such as the Numeric Pain Rating Scale (NPRS) for pain evaluation, the Constant-Murley Score (CMS) for shoulder function, and the EuroQol EQ-5D 3L for health-related quality of life. Additionally, the PROMIS-29 Upper Extremity v2.0 will assess physical function, and shoulder range of motion (ROM) will be measured in abduction, anterior elevation, and external rotation.

Further assessments include the Coracoid Pain Test (CPT), Distension Test in Passive External Rotation (DTPER), and various clinical tests such as the Jobe Test, Neer Test, and Hawkins-Kennedy test. Psychological and functional assessments will be conducted using the Tampa Scale for Kinesiophobia (TSK-11), Pain Self-Efficacy Questionnaire (PSEQ), Global Rating of Change Score (GRoC), Work Ability Index (WAI), and Work Status. Healthcare service use, adverse effects, and the use of rescue therapy will also be monitored.

Exploratory prediction analyses will be performed to identify factors predicting SPADI scores, pain levels, shoulder ROM, and return to work outcomes at 3, 6, and 12 months. These analyses aim to determine which patients benefit most from the combined suprascapular nerve block (SSNB) and intra-articular corticosteroid injection (IACI) treatment.