Clinical trial NCT05299242: The Anti-Freaze-F Study- "Anti-TNF for Treatment of Frozen Shoulder - a Feasibility Study"
Official title: Anti-TNF (Adalimumab) Injection for the Treatment of Adults With Frozen Shoulder During the Pain-predominant Phase: a Multi-centre, Randomised, Double Blind, Parallel Group, Feasibility Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Frozen Shoulder
Keywords: Adhesive capsulitis
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
name: 180 Life Sciences
First posted: 2022-03-28
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Participants will be randomised to either receive Adalimumab or Placebo.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants Eligible With Pain Predominant Frozen Shoulder
timeFrame: 3 Months
measure: Number of Participants Consenting to be Included in the Trial
timeFrame: 3 Months
measure: Time From Randomisation to First Injection
timeFrame: 2 weeks
measure: Time From First Injection to Second Injection
timeFrame: 6 weeks
measure: Shoulder Pain and Disability Index (SPADI) Score
timeFrame: Baseline and 3 months
Secondary outcomes:
measure: Pain (Shoulder Pain And Disability Index, 5-item Subscale)
timeFrame: Baseline and 3 months
measure: Function (Shoulder Pain And Disability Index, 8-item Subscale)
timeFrame: Baseline and 3 months
measure: Fear Avoidance Belief Questionnaire
timeFrame: Baseline and 3 months
measure: Pain Self Efficacy Questionnaire
timeFrame: Baseline and 3 months
measure: Insomnia Severity Index
timeFrame: Baseline and 3 months
measure: Return to Desired Activities (RDA)
timeFrame: Baseline and 3 months
measure: Global Impression of Change
timeFrame: 3 months
measure: Health Resource Use
timeFrame: 3 months
measure: Adverse Events Graded 3 or Above
timeFrame: Consent to 3 months follow-up
measure: Shoulder Range of Movement
timeFrame: Baseline and 3 months
Other outcomes:
Locations:
city: Sutton Coldfield
country: United Kingdom
facility: Good Hope Hospital
state: Birmingham
city: Saint Leonards-on-Sea
country: United Kingdom
facility: Conquest Hospital
state: Hastings
city: Grantham
country: United Kingdom
facility: Grantham & District Hospital, United Lincolnshire Hospitals
state: Lincolnshire
city: West Bromwich
country: United Kingdom
facility: Sandwell General Hospital
state: West Midlands
Study officials:
affiliation: University of Oxford
name: Jagdeep Nanchahal
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hopewell S, Kenealy N, Knight R, Rangan A, Dutton S, Srikesavan C, Feldmann M, Lamb S, Nanchahal J. Anti-TNF (adalimumab) injection for the treatment of adults with frozen shoulder during the pain predominant stage protocol for a multi-centre, randomised, double blind, parallel group, feasibility trial. NIHR Open Res. 2023 Apr 24;2:28. doi: 10.3310/nihropenres.13275.2. eCollection 2022.