The Anti-Freaze-F Study- "Anti-TNF for Treatment of Frozen Shoulder - a Feasibility Study"

Phase 2

Completed

• Conditions: Frozen Shoulder
• Interventions: Drug: Adalimumab Injection; Drug: Placebo

• Registration Number: NCT05299242
• Lead Sponsor: University of Oxford

Brief Summary

Frozen shoulder is a common condition affecting approximately 9% of people aged 25-64 years. During the early phase the pain is usually unbearable and the later restriction in movement is severely limiting. It occurs when the flexible tissue (capsule) that surrounds the shoulder joint becomes inflamed, thickened and tight. The pain can be very severe and lasts 3-9 months, followed by a 4-12 month period of increasing stiffness, after which the condition usually improves. Frozen shoulder often affects a person's ability to sleep, carry out everyday activities, and work. Current treatments include rest, painkillers, anti-inflammatories, physiotherapy and steroid injections. If stiffness persists, surgery is sometimes recommended. However, there is no evidence that any of these treatments lead to significant benefit in the long term, with many being ineffective. The aim of this study is to find out if it is possible to run a larger trial to test whether an injection of adalimumab can reduce pain and prevent the disease from getting worse, if given during the early painful phase of frozen shoulder. The investigators need to conduct this smaller study first to be sure it's possible to identify and treat people with early stage frozen shoulder, before they conduct a much larger trial to find out if this treatment works.

In this study the investigators will include 84 adults from 5 sites with painful early stage frozen shoulder who have not yet received treatment. People will be randomised to receive either an injection of the drug adalimumab or a dummy injection of saline (placebo) directly into the shoulder joint, both guided by ultrasound. All participants will also receive standardized advice on how to manage their shoulder pain. The investigators will assess participants before treatment and three months later. Adalimumab has been used very successfully to treat other inflammatory diseases such as rheumatoid arthritis. This study has been funded by the NIHR RfPB programme and 180 Life Sciences.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-02-17
• Study First Submitted QC: 2022-03-17
• Study First Posted: 2022-03-28
• Study Start: 2022-07-21
• Status Verified: 2022-11
• Primary Completion: 2023-05-09
• Study Completion: 2023-06-12
• Results First Submitted: 2024-07-10
• Results First Submitted QC: 2024-12-11
• Last Update Submitted: 2024-12-11
• Results First Posted: 2025-01-27
• Last Update Posted: 2025-01-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 9

Inclusion Criteria

1. Men and women aged 18 years and above.
2. With a new episode of shoulder pain attributable to pain-predominant stage of frozen shoulder (i.e. within approximately 3 months of onset of symptoms) diagnosed using criteria set out in the BESS guidelines (33) (Appendix 1);
3. Who are not being considered for surgery;
4. Able to understand spoken and written English;
5. Willing and able to give informed consent for trial participation and comply with all study requirements and time line;
6. Willing to allow his or her General Practitioner be notified of participation in the trial.
7. If female and of child-bearing potential OR if male and their partner is of child-bearing potential - willing to use effective contraception throughout the treatment period and for 5 months after the last injection.-

Exclusion Criteria

1. Those with frozen shoulder secondary to significant shoulder trauma (e.g., dislocation, fracture or full thickness tear requiring surgery) or other causes (e.g. recent breast cancer surgery or radiotherapy);
2. Those with a neurological disease affecting the shoulder;
3. Those with bilateral concurrent frozen shoulder;
4. Those with other shoulder disorders (e.g., inflammatory arthritis, rotator cuff disorders, glenohumeral joint instability) or with red flags consistent with the criteria set out in the BESS guidelines (33);
5. Those who have received corticosteroid injection for shoulder pain in the last 12 weeks to either shoulder;
6. Those currently taking any anti-TNF drug;
7. Those being treated with coumarin anticoagulants, such as warfarin;
8. Those who have participated in another research study involving an investigational medicinal product in the past 12 weeks;
9. Those with significant renal or hepatic impairment;
10. Those with contra-indications to anti-TNF injection:

10.1 Known allergy to any anti-TNF agent or any of the excipients; 10.2 Known Active tuberculosis (TB) or history of TB. 10.3 Known Active infection (chronic or localised) or known history of recurring infections or condition which may predispose patients to infection, including the use of concomitant immunosuppressive medications; 10.4 Known Moderate to severe heart failure (NYHA class III/IV); 10.5 Those known to have HIV, Hepatitis B or C; 10.6 Those at risk of Hepatitis B infection; 10.7 Those diagnosed with Multiple Sclerosis (MS) or other central or peripheral nervous system demyelinating disorders; 10.8 Those who have ever been diagnosed with cancer, except basal cell carcinoma (BCC); 10.9 Those requiring live vaccination prior to within 12 weeks after of the last trial injection or within the 4 weeks prior to randomisation; 10.10 Those taking biologic DMARDS; 10.11 Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Arm A	Adalimumab Injection	Participants will receive 2 injections of adalimumab. First injection: 160mg in 3.2ml Second injection approximately 2-3 weeks later 80mg in 1.6ml
Arm B	Placebo	Participants will receive 2 injections of placebo First injection: 3.2ml Second injection approximately 2-3 weeks later 1.6ml

Primary Outcome Measures

Name	Time	Method
Number of Participants Eligible With Pain Predominant Frozen Shoulder	3 Months	Ability to screen and identify potential participants with pain-predominant early stage frozen shoulder (i.e. within approximately 3 months of onset of symptoms).
Number of Participants Consenting to be Included in the Trial	3 Months	Willingness of eligible participants to consent and be randomised to intervention.
Time From Randomisation to First Injection	2 weeks	Practicalities of delivering the intervention, including time to first injection (within 2 weeks of randomisation).
Time From First Injection to Second Injection	6 weeks	Practicalities of delivering the intervention, including time between first injection and second injection (within 4-6 weeks of randomisation).
Shoulder Pain and Disability Index (SPADI) Score	Baseline and 3 months	Score ranges from 0 to 100, lower scores indicate better outcome.

Secondary Outcome Measures

Name	Time	Method
Pain Self Efficacy Questionnaire	Baseline and 3 months	Score ranges from 0 to 12, higher scores indicate better outcomes.
Pain (Shoulder Pain And Disability Index, 5-item Subscale)	Baseline and 3 months	Score ranges from 0 to 100, lower scores indicate better outcome.
Function (Shoulder Pain And Disability Index, 8-item Subscale)	Baseline and 3 months	Score ranges from 0 to 100, lower scores indicate better outcome.
Fear Avoidance Belief Questionnaire	Baseline and 3 months	Score ranges from 0 to 24, higher scores indicate better outcomes.
Insomnia Severity Index	Baseline and 3 months	Sleep disturbance measured using the Insomnia Severity Index, score ranges from 0 to 28, higher scores indicate worse outcomes.
Return to Desired Activities (RDA)	Baseline and 3 months	Return to desired activities measured using an adapted version of the Disabilities of the Arm, Shoulder and Hand (QUICKDASH) questionnaire. Score ranges from 3 to 15, lower scores indicate better outcomes.
Global Impression of Change	3 months	This was measured using the Likert scale. Score ranges from -5 (very much worse) to +5 (completely recovered) with a value of 0 suggesting no change. Higher scores indicate better outcomes.
Health Resource Use	3 months	Consultation with primary and secondary care, additional physiotherapy, injection use, or alternative therapies for index shoulder
Adverse Events Graded 3 or Above	Consent to 3 months follow-up	Any adverse event (graded 3 or above) that has resulted from the trial.; The Common Terminology Criteria for Adverse Events (CTCAE) v5.0 was used to guide recording adverse events including grading of the event. Grade 3: Severe symptoms or medically significant but not life-threatening but may be disabling or limit self care in Activities of Daily Living. Grade 4: Life threatening consequences; urgent or emergent intervention needed. Grade 5: Death related to or due to adverse event.
Shoulder Range of Movement	Baseline and 3 months	Clinician assessed (goniometry measured) active shoulder flexion, extension, abduction, internal and external rotation. Range of flexion and abduction: 0-180 degrees. Range of extension, internal rotation and external rotation: 0-90 degrees.

Trial Locations

Locations (4)

Grantham & District Hospital, United Lincolnshire Hospitals; 🇬🇧 Grantham, Lincolnshire, United Kingdom

Conquest Hospital; 🇬🇧 Saint Leonards-on-Sea, Hastings, United Kingdom

Good Hope Hospital; 🇬🇧 Sutton Coldfield, Birmingham, United Kingdom

Sandwell General Hospital; 🇬🇧 West Bromwich, West Midlands, United Kingdom