Comparison of Ultrasound-Guided Subacromial Vs. Systemic Steroid Injections for Frozen Shoulder: a Multicenter Pilot Study

Phase 2

Recruiting

• Conditions: Frozen Shoulder
• Interventions: Drug: Compound betamethasone Injection(Subacromial Ultrasound Guided injection); Drug: Compound betamethasone Injection(Gluteal muscle injection); Other: Normal Saline as Placebo (ultrasound-guided subacromial injection); Other: Normal Saline as Placebo (gluteal muscle inection); Behavioral: home exercise

• Registration Number: NCT06626568
• Lead Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Brief Summary

The goal of this multicenter pilot study is to validate the effectiveness of extending the injection interval between betamethasone doses from one to two weeks for treating frozen shoulder (adhesive capsulitis) in adults aged 18 to 75. This study also aims to screen potential study centers and gather data to refine the sample size calculation for a larger, future trial. The main questions it aims to answer are:

* Does extending the interval between injections maintain effectiveness in improving shoulder function and reducing pain for frozen shoulder?

* Which centers in this pilot study are qualified for a larger, future trial?

* What is the appropriate sample size for conducting a multicenter RCT study with the same research design at the selected centers?

Participants will:

* Receive 3 injections over 4 weeks and will be followed up for another 8 weeks

* Complete shoulder function assessments

* Perform home rehabilitation exercises

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-09
• Study First Submitted: 2024-09-29
• Study First Submitted QC: 2024-10-03
• Study First Posted: 2024-10-04
• Study Start: 2024-10-15
• Last Update Submitted: 2025-02-04
• Last Update Posted: 2025-02-07
• Primary Completion: 2025-09
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. History of ≤9 months, clinically diagnosed with primary frozen shoulder (including frozen shoulder associated with diabetes).
2. Aged between 18 and 75 years old
3. Pain NRS score ≥4
4. Measured passive range of motion of the affected shoulder in at least two of the three directions (forward flexion, external rotation with arm at the side, and internal rotation with arm at the side) is reduced by 25% or more compared to the contralateral normal shoulder.
5. Exclusion of osteoarthritis, dislocation, and other shoulder abnormalities through X-ray and MRI of the affected shoulder.

Exclusion Criteria

1. Secondary frozen shoulder caused by thyroid disease, cardiovascular disease, cancer, stroke, radiotherapy, neurosurgery, or breast surgery (excluding diabetes); secondary frozen shoulder caused by major shoulder trauma requiring medical care (e.g., fractures, dislocations, rotator cuff tears).
2. Full-thickness rotator cuff tear in the affected shoulder confirmed by MRI (excluding rotator cuff tendinopathy and partial-thickness rotator cuff tear in patients with frozen shoulder without a history of major shoulder trauma).
3. Patients unable to undergo MRI due to financial reasons, claustrophobia, pacemaker, or other metallic implants in the body.
4. Local infection in the affected shoulder or other contraindications to shoulder injections.
5. Patients with contraindications to steroid therapy (e.g., poorly controlled blood sugar in diabetes).
6. Patients with frozen shoulder who have already undergone shoulder injections, manipulation under anesthesia, arthroscopic capsular release, or open surgery for capsular release.
7. Received any form of steroid treatment within the past 3 months.
8. History of glucocorticoid use for more than 3 months.
9. Bilateral frozen shoulder or a history of frozen shoulder in the contralateral shoulder.
10. Pregnant or breastfeeding women.
11. Patients lacking the cognitive ability to comply with the study protocol.
12. Patients not residing in the area where the study is being conducted.
13. Patients with compensation claims or legal disputes related to workplace injury or car accidents.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
subacromial injection	Compound betamethasone Injection(Subacromial Ultrasound Guided injection)	gluteal injection of 5 ml normal saline at week 0,2,4, ultrasound-guided subacromial injection of 1 ml of Compound betamethasone and 4 ml of normal saline at week 0,2,4. The participants were instructed to perform home rehabilitation exercise for 12 weeks. 30 minutes of home-based self-rehabilitation exercises in the morning, afternoon, and evening, with a total of 90 minutes per day. Standard instructional videos and demonstrations by outpatient rehabilitation therapists are provided to participants. Each exercise, including wall-climbing, table-climbing, and back-climbing, should be performed for 10 minutes, with a total of 30 minutes per session.
gluteal injection	Compound betamethasone Injection(Gluteal muscle injection)	gluteal injection of 1 ml of Compound betamethasone and 4 ml of normal saline at week 0,2,4, ultrasound-guided subacromial injection of 5 ml of normal saline at week 0,2,4. The participants were instructed to perform home rehabilitation exercise for 12 weeks. 30 minutes of home-based self-rehabilitation exercises in the morning, afternoon, and evening, with a total of 90 minutes per day. Standard instructional videos and demonstrations by outpatient rehabilitation therapists are provided to participants. Each exercise, including wall-climbing, table-climbing, and back-climbing, should be performed for 10 minutes, with a total of 30 minutes per session.
gluteal injection	Normal Saline as Placebo (ultrasound-guided subacromial injection)	gluteal injection of 1 ml of Compound betamethasone and 4 ml of normal saline at week 0,2,4, ultrasound-guided subacromial injection of 5 ml of normal saline at week 0,2,4. The participants were instructed to perform home rehabilitation exercise for 12 weeks. 30 minutes of home-based self-rehabilitation exercises in the morning, afternoon, and evening, with a total of 90 minutes per day. Standard instructional videos and demonstrations by outpatient rehabilitation therapists are provided to participants. Each exercise, including wall-climbing, table-climbing, and back-climbing, should be performed for 10 minutes, with a total of 30 minutes per session.
gluteal injection	home exercise	gluteal injection of 1 ml of Compound betamethasone and 4 ml of normal saline at week 0,2,4, ultrasound-guided subacromial injection of 5 ml of normal saline at week 0,2,4. The participants were instructed to perform home rehabilitation exercise for 12 weeks. 30 minutes of home-based self-rehabilitation exercises in the morning, afternoon, and evening, with a total of 90 minutes per day. Standard instructional videos and demonstrations by outpatient rehabilitation therapists are provided to participants. Each exercise, including wall-climbing, table-climbing, and back-climbing, should be performed for 10 minutes, with a total of 30 minutes per session.
subacromial injection	Normal Saline as Placebo (gluteal muscle inection)	gluteal injection of 5 ml normal saline at week 0,2,4, ultrasound-guided subacromial injection of 1 ml of Compound betamethasone and 4 ml of normal saline at week 0,2,4. The participants were instructed to perform home rehabilitation exercise for 12 weeks. 30 minutes of home-based self-rehabilitation exercises in the morning, afternoon, and evening, with a total of 90 minutes per day. Standard instructional videos and demonstrations by outpatient rehabilitation therapists are provided to participants. Each exercise, including wall-climbing, table-climbing, and back-climbing, should be performed for 10 minutes, with a total of 30 minutes per session.
subacromial injection	home exercise	gluteal injection of 5 ml normal saline at week 0,2,4, ultrasound-guided subacromial injection of 1 ml of Compound betamethasone and 4 ml of normal saline at week 0,2,4. The participants were instructed to perform home rehabilitation exercise for 12 weeks. 30 minutes of home-based self-rehabilitation exercises in the morning, afternoon, and evening, with a total of 90 minutes per day. Standard instructional videos and demonstrations by outpatient rehabilitation therapists are provided to participants. Each exercise, including wall-climbing, table-climbing, and back-climbing, should be performed for 10 minutes, with a total of 30 minutes per session.

Primary Outcome Measures

Name	Time	Method
Shoulder Pain and Disability Index (SPADI)	Baseline and 12 weeks	The SPADI score ranges from 0 to 100. A score of 0 indicates no pain or disability, while a score of 100 reflects the worst possible pain and maximum functional disability in the shoulder.; Data entry will be performed by blinded research staff. They will present the paper CRF sample form to the participants and ask questions one by one, directly entering the responses of participants into the corresponding electronic CRF form in the EDC system using handheld electronic devices (such as smartphones, tablets, or laptops).

Secondary Outcome Measures

Name	Time	Method
progression rate of rotator cuff tears	From enrollment to the end of follow-up at 12 weeks	Third-party experts will conduct blinded readings of shoulder MRI scans, classifying rotator cuff status into three grades: Grade I (intact), Grade II (partial tear), and Grade III (complete tear). Patients classified as Grade III at week 0 will be excluded from the study, as baseline grading (determined by each research center) assesses eligibility per exclusion criterion 2. The lead center provided MRI reading training to all centers, using T2-weighted images with a pure white fluid signal occupying full or partial thickness of the rotator cuff across at least two consecutive MRI slices as the diagnostic criterion for full- or partial-thickness tears. Patients with Grade I or II tears at week 0 will receive study treatment and be followed up at week 12. Tear progression is defined as an increase of at least one grade between weeks 0 and 12, assessed by blinded experts. The progression rate is the number of subjects with progression divided by the total number in each group.
short version of Disabilities of the Arm, Shoulder, and Hand Questionnaire (QuickDASH）	Baseline and 12 weeks	The QuickDASH score ranges from 0 to 100. A score of 0 means no disability, and a score of 100 signifies the highest level of disability related to arm, shoulder, and hand function.; Data entry will be performed by blinded research staff. They will present the paper CRF sample form to the participants and ask questions one by one, directly entering the responses of participants into the corresponding electronic CRF form in the EDC system using handheld electronic devices (such as smartphones, tablets, or laptops).
Numerical Rating Scale (NRS)	Baseline and 12 weeks	The NRS score ranges from 0 to 10. A score of 0 indicates no pain, while a score of 10 reflects the worst possible pain.; Data entry will be performed by blinded research staff. They will present the paper CRF sample form to the participants and ask questions one by one, directly entering the responses of participants into the corresponding electronic CRF form in the EDC system using handheld electronic devices (such as smartphones, tablets, or laptops).
five-level EuroQol five-dimensional questionnaire (EQ-5D-5L)	Baseline and 12 weeks	The EQ-5D-5L provides an overall health utility score ranging from -0.281 to 1, where 1 represents perfect health, zero represents a state equivalent to death, and negative values indicate health states worse than death.; It also reports on five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each rated on five levels from no problems to extreme problems.; Data entry will be performed by blinded research staff. They will present the paper CRF sample form to the participants and ask questions one by one, directly entering the responses of participants into the corresponding electronic CRF form in the EDC system using handheld electronic devices (such as smartphones, tablets, or laptops).
passive range of motion of shoulder	Baseline and 12 weeks	The passive range of motion for shoulder flexion, abduction, internal rotation (at the side), and external rotation (at the side) on the affected side will be measured using a goniometer by trained researchers following a pre-established standard operating procedure.
Direct Medical Cost	Week8 and week12	The costs of healthcare resources used for the diagnosis and treatment of frozen shoulder of the participant, including medication fees, medical expenses, testing fees, nursing fees and hospitalization costs. The questionnaire surveys the cost by the participant since the last outpatient research follow-up.
work absenteeism	Week 8 and Week 12	The questionnaire surveys the number of workdays missed by the subject since the last outpatient research follow-up.
Unplanned concomitant use of analgesics	Week 12	This questionnaire surveys the usage of unplanned concomitant analgesic medications by the subject since the last outpatient research follow-up.
Glycated Hemoglobin (HbA1c)	week 0 and week 12	Depending on the specific assay methods used by the laboratory departments of different study centers, HbA1c will be measured by high-Performance Liquid Chromatography (HPLC), Immunoturbidimetric Method, Enzymatic Method, Affinity Chromatography, Electrophoresis, Capillary Electrophoresis or Ion-Exchange Chromatography.
glycated albumin	week 0 and week 4	Depending on the specific assay methods used by the laboratory departments of different study centers, glycated albumin will be measured by Enzymatic Method, Immunoturbidimetric Method, High-Performance Liquid Chromatography (HPLC), Affinity Chromatography, or Immunoelectrophoresis.

Trial Locations

Locations (9)

Guangde County People's Hospital; 🇨🇳 Xuancheng, Anhui, China

Army Specialty Medical Center of the People's Liberation Army of China; 🇨🇳 Chongqing, Chongqing, China

Yangpu District Central Hospital of Shanghai; 🇨🇳 Shanghai, Shanghai, China

Second Affiliated Hospital, School of Medicine, Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China

The First People's Hospital of Linping District, Hangzhou; 🇨🇳 Hangzhou, Zhejiang, China

First Affiliated Hospital of Ningbo University; 🇨🇳 Ningbo, Zhejiang, China

Xiangshan County Traditional Chinese Medicine Hospital Healthcare Group; 🇨🇳 Ningbo, Zhejiang, China

Pujiang People's Hospital; 🇨🇳 Pujiang, Zhejiang, China

Shengzhou People's Hospital; 🇨🇳 Shaoxing, Zhejiang, China