Ultrasound-Guided Intra-Articular vs Gluteal Intramuscular Corticosteroid Injection for Frozen Shoulder (CUSIS-FS)

Ultrasound-Guided Intra-Articular Versus Systemic Corticosteroid Injection for Frozen Shoulder: A Multicenter, Blinded, Randomized Controlled Trial

The goal of this clinical trial is to determine if a gluteal muscle injection of compound betamethasone is as effective as an ultrasound-guided intra-articular injection in treating frozen shoulder (adhesive capsulitis) in adults aged 18 to 65. The main questions it aims to answer are:

• Is gluteal injection as effective as ultrasound-guided intra-articular injection for improving shoulder function and reducing pain?
• What are the side effects of each treatment method? Researchers will compare these two injection methods.

Participants will:

• Receive one injection at baseline and will be followed up for 12 weeks
• Complete shoulder function assessments
• Perform home rehabilitation exercises

Study Overview

• Status: Recruiting
• Conditions: Frozen Shoulder
• Intervention / Treatment: Drug: Compound betamethasone injection (dorsogluteal intramuscular); Drug: 0.9% sodium chloride injection (ultrasound-guided intra-articular glenohumeral placebo); Other: Standardized home-based shoulder rehabilitation exercise program; Drug: Compound betamethasone injection (ultrasound-guided intra-articular glenohumeral); Drug: 0.9% sodium chloride injection (dorsogluteal intramuscular placebo)

• Study Type: Interventional
• Enrollment (Estimated): 528
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Bin Han, Medical Doctor; Phone Number: +86-13735402700; Email: icydoctor@zju.edu.cn

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200082
      • Not yet recruiting
      • Yangpu District Central Hospital of Shanghai
      • Contact: Huaming Xue, Medical Doctor; Phone Number: +86-18964859835; Email: x11h22m33@126.com
      • Principal Investigator: Huaming Xue, Medical Doctor
      • Sub-Investigator: Xuefeng Lei, Medical Master
      • Sub-Investigator: Long Xue, Medical Master
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Recruiting
      • Second Affiliated Hospital, School of Medicine, Zhejiang University
      • Contact: Bin Han, Medical Doctor; Phone Number: +86-13735402700; Email: icydoctor@zju.edu.cn
      • Principal Investigator: Bin Han, Medical Doctor
      • Sub-Investigator: Zhuolin Zhong, Medical Master
    • Hangzhou, Zhejiang, China, 310000
      • Not yet recruiting
      • The Third Affiliated hospital of Zhejiang Chinese Medical University
      • Contact: Yuepeng Xie, Medical Master; Phone Number: 86-15988115953; Email: 421522908@qq.com
      • Principal Investigator: Yuepeng Xie, Medical Master
      • Sub-Investigator: Yilei Jin, Bachelor of Science
      • Sub-Investigator: Linfang Zhao, Medical Master
    • Hangzhou, Zhejiang, China, 311199
      • Not yet recruiting
      • The First People's Hospital of Linping District, Hangzhou
      • Contact: Shenghua Wu, Medical Bachelor; Phone Number: +86-13372503239; Email: shenghuawu022@gmail.com
      • Principal Investigator: Shenghua Wu, Medical Bachelor
      • Sub-Investigator: Xiaobin Li, Medical Master
      • Sub-Investigator: Xiufeng Kuang, Medical Master
    • Huzhou, Zhejiang, China, 313000
      • Recruiting
      • Huzhou Central Hospital
      • Contact: Jianyou Li, Medical Doctor; Phone Number: +86-13857255511; Email: ljywn1977@126.com
      • Contact: Fengfeng Wu, Medical Doctor; Phone Number: +86-13567289166; Email: wufengfeng@zju.edu.cn
      • Principal Investigator: Jianyou Li, Medical Doctor
      • Principal Investigator: Fengfeng Wu, Medical Doctor
      • Sub-Investigator: Shiyun Shen, Medical Master
      • Sub-Investigator: Yunsheng Han, Medical Bachelor
      • Sub-Investigator: Qinguang Xu, Medical Doctor
      • Sub-Investigator: Li Chen, Medical Master
    • Jinhua, Zhejiang, China, 322200
      • Not yet recruiting
      • Pujiang People's Hospital
      • Contact: Hongpeng Jian, Medical Bachelor; Phone Number: +86-18757991192; Email: 630166613@qq.com
      • Principal Investigator: Hongpeng Jian, Medical Bachelor
      • Sub-Investigator: Xiujuan Xu, Medical Bachelor
      • Sub-Investigator: Muhan Hong, Medical Bachelor
    • Ningbo, Zhejiang, China, 315799
      • Not yet recruiting
      • Xiangshan County Traditional Chinese Medicine Hospital Healthcare Group
      • Contact: Lei Zhang, Medical Master; Phone Number: +86-18858222839; Email: 675244086@qq.com
      • Principal Investigator: Lei Zhang, Medical Master
      • Sub-Investigator: Yuqiong Gao, Medical Bachelor
      • Sub-Investigator: Dong Sun, Medical Bachelor
    • Ningbo, Zhejiang, China, 315020
      • Recruiting
      • First Affiliated Hospital of Ningbo University
      • Contact: Yunfeng Mi, Medical Doctor; Phone Number: +86-15968412281; Email: bee-cloud@163.com
      • Principal Investigator: Yunfeng Mi, Medical Doctor
      • Sub-Investigator: Shaojie Zhou, Medical Bachelor
      • Sub-Investigator: Yinfeng Hu, Medical Master
    • Shanhu, Zhejiang, China, 312400
      • Not yet recruiting
      • Shengzhou People's Hospital
      • Contact: Haidong Zhou, Medical Master; Phone Number: +86-13858567997; Email: haidongzhou@qq.com
      • Principal Investigator: Haidong Zhou, Medical Master
      • Sub-Investigator: Lizhong Ren, Medical Bachelor
      • Sub-Investigator: Yun Wang, Medical Master

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria (all must be met):

1. Symptom duration ≤9 months; clinically diagnosed unilateral primary (idiopathic) frozen shoulder (including diabetes-associated frozen shoulder).
2. Age 18 to 65 years.
3. Worst shoulder pain in the past 24 hours (NRS-WP, 0-10) ≥4.
4. Passive range of motion (ROM) limitation of the affected shoulder: compared with the contralateral normal shoulder, a decrease of ≥30° in at least two of the following three directions: forward flexion, abduction, and external rotation with the arm at the side.
5. Radiographic exclusion of other shoulder pathology: Affected-shoulder anteroposterior (AP) radiograph excludes glenohumeral osteoarthritis, calcific tendinopathy, and other structural abnormalities; and axillary view and/or scapular Y (outlet) or transthoracic view excludes glenohumeral dislocation.

Exclusion Criteria (any of the following):

1. Secondary frozen shoulder due to thyroid disease, cardiovascular disease, stroke, radiotherapy, prior neurosurgical or breast surgery, etc. (diabetes excluded from this item); or frozen shoulder secondary to major shoulder trauma requiring medical care (e.g., fracture, dislocation, rotator cuff tear).
2. Confirmed or highly suspected full-thickness or massive rotator cuff tear causing functional pseudoparalysis (e.g., positive Jobe test with marked strength loss).
3. Local infection of the affected shoulder or any contraindication to shoulder injection (e.g., uncorrected bleeding risk/coagulopathy).
4. Contraindication to corticosteroid therapy (e.g., poorly controlled diabetes, systemic infection).
5. Prior manipulation under anesthesia, arthroscopic capsular release, or open surgical release for frozen shoulder on the affected shoulder.
6. Any corticosteroid treatment via any route within the past 3 months (including shoulder injection).
7. Requires long-term or intermittent corticosteroid use for other conditions (e.g., autoimmune disease such as rheumatoid arthritis, acute asthma exacerbations).
8. Bilateral frozen shoulder, or contralateral history of frozen shoulder not yet fully recovered.
9. Conditions significantly affecting upper-limb function assessment or ability to perform rehabilitation (e.g., marked limb disability).
10. Pregnant or breastfeeding.
11. Lacks the cognitive ability to comply with study procedures.
12. Does not reside in the region served by the participating hospital(s) (anticipated inability to complete follow-up).
13. Compensation claims (e.g., work-related injury, traffic accident) or ongoing legal disputes/litigation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Systemic steroid / Gluteal injection; At Week 0 (baseline), participants receive a single dorsogluteal intramuscular injection of compound betamethasone injection 1 mL diluted with 0.9% sodium chloride 4 mL (total volume 5 mL), plus a single ultrasound-guided intra-articular glenohumeral injection of 0.9% sodium chloride 5 mL (placebo) as part of a double-dummy design. All participants follow a standardized home-based shoulder rehabilitation program for 12 weeks (approximately 40 minutes/day; twice daily, 20 minutes/session).	Drug: Compound betamethasone injection (dorsogluteal intramuscular); A single dorsogluteal intramuscular injection at Week 0 (baseline): compound betamethasone 1 mL mixed with 0.9% sodium chloride 4 mL (total volume 5 mL), as part of a double-dummy design.; Drug: 0.9% sodium chloride injection (ultrasound-guided intra-articular glenohumeral placebo); A single ultrasound-guided intra-articular glenohumeral placebo injection at Week 0 (baseline): 0.9% sodium chloride 5 mL, to mimic the local (intra-articular) injection in the double-dummy design.; Other: Standardized home-based shoulder rehabilitation exercise program; All participants perform a standardized home-based rehabilitation exercise program for 12 weeks after outpatient instruction, approximately 40 minutes per day (twice daily, 20 minutes per session), following the study-provided instructional video.
Active Comparator: Local steroid / Intra-articular injection; At Week 0 (baseline), participants receive a single ultrasound-guided intra-articular glenohumeral injection of compound betamethasone injection 1 mL diluted with 0.9% sodium chloride 4 mL (total volume 5 mL), plus a single dorsogluteal intramuscular injection of 0.9% sodium chloride 5 mL (placebo) as part of a double-dummy design. All participants follow a standardized home-based shoulder rehabilitation program for 12 weeks (approximately 40 minutes/day; twice daily, 20 minutes/session).	Other: Standardized home-based shoulder rehabilitation exercise program; All participants perform a standardized home-based rehabilitation exercise program for 12 weeks after outpatient instruction, approximately 40 minutes per day (twice daily, 20 minutes per session), following the study-provided instructional video.; Drug: Compound betamethasone injection (ultrasound-guided intra-articular glenohumeral); A single ultrasound-guided intra-articular glenohumeral injection at Week 0 (baseline): compound betamethasone 1 mL mixed with 0.9% sodium chloride 4 mL (total volume 5 mL), as part of a double-dummy design.; Drug: 0.9% sodium chloride injection (dorsogluteal intramuscular placebo); A single dorsogluteal intramuscular placebo injection at Week 0 (baseline): 0.9% sodium chloride 5 mL, to mimic the systemic (intramuscular) injection in the double-dummy design.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Shoulder Pain and Disability Index (SPADI) Total Score from Baseline to Week 8	Shoulder Pain and Disability Index (SPADI) total score (validated Simplified Chinese version; range 0-100, where 0 = no pain/disability and 100 = worst pain/disability; higher scores indicate worse outcome). Assessed at Weeks 0 (baseline), 2, 4, 8, and 12. Primary endpoint is the change from baseline to Week 8 (Week 8 minus Week 0); negative change indicates improvement.	Baseline (Week 0) to Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in QuickDASH Score from Baseline to Week 8	Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) score (official Simplified Chinese version; range 0-100, where 0 = no disability and 100 = most severe disability; higher scores indicate worse outcome). Assessed at Weeks 0 (baseline), 2, 4, 8, and 12. Endpoint is the change from baseline to Week 8 (Week 8 minus Week 0); negative change indicates improvement.	Baseline (Week 0) to Week 8
Change in EQ-5D-5L Index Score from Baseline to Week 8	EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) health utility index (Simplified Chinese version; index derived using the Chinese value set; range -0.391 to 1.000, where 1.000 = full health and higher scores indicate better health-related quality of life). Assessed at Weeks 0 (baseline), 2, 4, 8, and 12. Endpoint is the change from baseline to Week 8 (Week 8 minus Week 0); positive change indicates improvement.	Baseline (Week 0) to Week 8
Change in Worst Shoulder Pain in the Past 24 Hours (NRS-WP) from Baseline to Week 8	Worst shoulder pain in the past 24 hours measured by a Numeric Rating Scale (NRS) item from the Brief Pain Inventory-Chinese version (BPI-C) (range 0-10, where 0 = no pain and 10 = worst imaginable pain; higher scores indicate worse outcome). Assessed at Weeks 0 (baseline), 2, 4, 8, and 12. Endpoint is the change from baseline to Week 8 (Week 8 minus Week 0); negative change indicates improvement.	Baseline (Week 0) to Week 8
Change in Passive Shoulder Range of Motion (ROM) from Baseline to Week 8	Passive shoulder range of motion (ROM) of the affected shoulder assessed at Weeks 0 (baseline), 2, 4, 8, and 12. Passive flexion measured by goniometer (0-180 degrees; higher degrees indicate better ROM), passive abduction by goniometer (0-180 degrees; higher degrees indicate better ROM), and passive external rotation at side by goniometer (-20 to 90 degrees; higher degrees indicate better ROM). Passive internal rotation is recorded as a 1-18 score based on the highest spinal level reached by the thumb tip behind the back (1-12 = T1-T12, 13-17 = L1-L5, 18 = sacral region or below; lower score indicates better ROM). Endpoint is the change from baseline to Week 8 (Week 8 minus Week 0).	Week 0 (baseline) to Week 8
Change in SPADI Total Score from Baseline to Week 12	Shoulder Pain and Disability Index (SPADI) total score (range 0-100, where 0 = no pain/disability and 100 = worst pain/disability; higher scores indicate worse outcome). Assessed at Weeks 0 (baseline), 2, 4, 8, and 12. Endpoint is the change from baseline to Week 12 (Week 12 minus Week 0); negative change indicates improvement.	Baseline (Week 0) to Week 12
Change in QuickDASH Score from Baseline to Week 12	Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) score (range 0-100, where 0 = no disability and 100 = most severe disability; higher scores indicate worse outcome). Assessed at Weeks 0 (baseline), 2, 4, 8, and 12. Endpoint is the change from baseline to Week 12 (Week 12 minus Week 0); negative change indicates improvement.	Baseline (Week 0) to Week 12
Change in EQ-5D-5L Index Score from Baseline to Week 12	EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) health utility index (index derived using the Chinese value set; range -0.391 to 1.000; higher scores indicate better health-related quality of life). Assessed at Weeks 0 (baseline), 2, 4, 8, and 12. Endpoint is the change from baseline to Week 12 (Week 12 minus Week 0); positive change indicates improvement.	Baseline (Week 0) to Week 12
Change in Worst Shoulder Pain in the Past 24 Hours (NRS-WP) from Baseline to Week 12	Worst shoulder pain in the past 24 hours measured by Numeric Rating Scale (NRS) (range 0-10, where 0 = no pain and 10 = worst imaginable pain; higher scores indicate worse outcome). Assessed at Weeks 0 (baseline), 2, 4, 8, and 12. Endpoint is the change from baseline to Week 12 (Week 12 minus Week 0); negative change indicates improvement.	Baseline (Week 0) to Week 12
Change in Passive Shoulder ROM from Baseline to Week 12	Passive shoulder range of motion (ROM) of the affected shoulder assessed at Weeks 0 (baseline), 2, 4, 8, and 12. Passive flexion measured by goniometer (0-180 degrees; higher degrees indicate better ROM), passive abduction by goniometer (0-180 degrees; higher degrees indicate better ROM), and passive external rotation at side by goniometer (-20 to 90 degrees; higher degrees indicate better ROM). Passive internal rotation is recorded as a 1-18 score based on the highest spinal level reached by the thumb tip behind the back (1-12 = T1-T12, 13-17 = L1-L5, 18 = sacral region or below; lower score indicates better ROM). Endpoint is the change from baseline to Week 12 (Week 12 minus Week 0).	Baseline (Week 0) to Week 12
Change in SPADI Total Score over 12 Weeks (Longitudinal)	Shoulder Pain and Disability Index (SPADI) total score (range 0-100, where 0 = no pain/disability and 100 = worst pain/disability; higher scores indicate worse outcome). Assessed at Weeks 0 (baseline), 2, 4, 8, and 12. Longitudinal change in SPADI total score over 12 weeks will be evaluated; decreasing scores over time indicate improvement.	SPADI total score assessed at Weeks 0/2/4/8/12; longitudinal change over 12 weeks will be evaluated.
Change in QuickDASH Score over 12 Weeks (Longitudinal)	Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) score (range 0-100, where 0 = no disability and 100 = most severe disability; higher scores indicate worse outcome). Assessed at Weeks 0 (baseline), 2, 4, 8, and 12. Longitudinal change in QuickDASH score over 12 weeks will be evaluated; decreasing scores over time indicate improvement.	Baseline (Week 0), Week 2, Week 4, Week 8, and Week 12
Change in EQ-5D-5L Index Score over 12 Weeks (Longitudinal)	EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) health utility index (index derived using the Chinese value set; range -0.391 to 1.000; higher scores indicate better health-related quality of life). Assessed at Weeks 0 (baseline), 2, 4, 8, and 12. Longitudinal change in EQ-5D-5L index over 12 weeks will be evaluated; increasing scores over time indicate improvement.	Baseline (Week 0), Week 2, Week 4, Week 8, and Week 12
Change in Worst Shoulder Pain in the Past 24 Hours (NRS-WP) over 12 Weeks (Longitudinal)	Worst shoulder pain in the past 24 hours measured by Numeric Rating Scale (NRS) (range 0-10, where 0 = no pain and 10 = worst imaginable pain; higher scores indicate worse outcome). Assessed at Weeks 0 (baseline), 2, 4, 8, and 12. Longitudinal change in NRS over 12 weeks will be evaluated; decreasing scores over time indicate improvement.	Baseline (Week 0), Week 2, Week 4, Week 8, and Week 12
Change in Passive Shoulder Range of Motion (ROM) over 12 Weeks (Longitudinal)	Passive shoulder range of motion (ROM) of the affected shoulder assessed longitudinally at Weeks 0 (baseline), 2, 4, 8, and 12. Passive flexion measured by goniometer (0-180 degrees; higher degrees indicate better ROM), passive abduction by goniometer (0-180 degrees; higher degrees indicate better ROM), and passive external rotation at side by goniometer (-20 to 90 degrees; higher degrees indicate better ROM). Passive internal rotation is recorded as a 1-18 score based on the highest spinal level reached by the thumb tip behind the back (1-12 = T1-T12, 13-17 = L1-L5, 18 = sacral region or below; lower score indicates better ROM). Longitudinal change over 12 weeks will be evaluated.	Baseline (Week 0), Week 2, Week 4, Week 8, and Week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of at Least One Serious Adverse Event (SAE)	Counts and proportion of participants experiencing ≥1 SAE during the 12-week follow-up	Up to 12 weeks
Incidence of at Least One Adverse Event (AE)	Counts and proportion of participants experiencing ≥1 AE during the 12-week follow-up.	Up to 12 weeks
Incidence of Injection-related Local Adverse Events	Incidence of injection-related local adverse events during follow-up, including pre-defined, systematically assessed local AEs (AESI; solicited at scheduled visits) (e.g., marked post-injection shoulder pain flare, local infection, skin/subcutaneous changes) and investigator-attributed injection-related local AEs identified non-systematically (unsolicited reports/clinical assessment/medical record review), including injection-related events not pre-specified as AESI.	Up to 12 weeks
Incidence of Injection-related Systemic Adverse Events	Incidence of injection-related systemic adverse events during follow-up, including pre-defined, systematically assessed systemic AEs (AESI; solicited at scheduled visits) (e.g., facial flushing, mood/sleep changes, gastrointestinal discomfort, transient hyperglycemia/hypertension, suspected adrenal suppression) and investigator-attributed injection-related systemic AEs identified non-systematically (unsolicited reports/clinical assessment/medical record review), including injection-related events not pre-specified as AESI.	Up to 12 weeks

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Principal Investigator: Bin Han, Medical Doctor, The 2nd Affiliated Hospital of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2026
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): January 1, 2031

Study Registration Dates

• First Submitted: February 11, 2026
• First Submitted That Met QC Criteria: February 11, 2026
• First Posted (Actual): February 18, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: intramuscular injection; ultrasound guidance; intra-articular injection; frozen shoulder; compound betamethasone
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Joint Diseases; Bursitis; Inorganic Chemicals; Chlorine Compounds; Sodium Compounds; Chlorides; Hydrochloric Acid; Sodium Chloride
• Other Study ID Numbers: 2024-0434

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Analytic dataset sufficient to reproduce the primary publication results (deidentified IPD with data dictionary and derivation specifications) and scripts for main tables/figures;; Full analyzable dataset sufficient to support protocol-specified primary/secondary outcomes and prespecified subgroup/sensitivity analyses (deidentified IPD with data dictionary and derivation specifications).
• IPD Sharing Time Frame: Analytic dataset: beginning 6 months after online publication of the primary results; Full analyzable dataset: beginning 12 months after online publication; Both available until 5 years after online publication of the primary results.
• IPD Sharing Access Criteria: Proposals from bona fide researchers will be reviewed by the Data Access Committee (DAC); approved requestors must execute a Data Use Agreement (DUA) and access data via a secure environment; no redistribution or re-identification.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No