Frozen ShoulderPhase 2/3Anti-FreazeFNCT05299242
The Anti-Freaze-F Study- "Anti-TNF for Treatment of Frozen Shoulder - a Feasibility Study"
A Phase 2/3 study testing Adalimumab Injection in people with Frozen Shoulder, run by University of Oxford at 4 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Frozen Shoulder
- What is being tested?
- Adalimumab Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9 participants
- Where
- 4 sitesUnited Kingdom
- Study dates
- 21 Jul 2022to 12 Jun 2023
- Phase
- Phase 2/3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women aged 18 years and above.
- 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);
- Who are not being considered for surgery;
- Able to understand spoken and written English;
- Willing and able to give informed consent for trial participation and comply with all study requirements and time line;
- Willing to allow his or her General Practitioner be notified of participation in the trial.
- 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.-
Who cannot join
- 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);
- Those with a neurological disease affecting the shoulder;
- Those with bilateral concurrent frozen shoulder;
- 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);
- Those who have received corticosteroid injection for shoulder pain in the last 12 weeks to either shoulder;
- Those currently taking any anti-TNF drug;
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- Those being treated with coumarin anticoagulants, such as warfarin;
- Those who have participated in another research study involving an investigational medicinal product in the past 12 weeks;
- Those with significant renal or hepatic impairment;
- 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
Trial locations and contacts
4 sites in 1 country.
United Kingdom4 sites
Grantham & District Hospital, United Lincolnshire Hospitals
Grantham, Lincolnshire, NG31 8DG
Conquest Hospital
Saint Leonards-on-Sea, Hastings, TN37 7RD
Good Hope Hospital
Sutton Coldfield, Birmingham, B75 7RR
Sandwell General Hospital
West Bromwich, West Midlands, B71 4HJ
About this 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
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.
- Conditions
- Frozen Shoulder
- Being tested
- Adalimumab Injection, Placebo
- Keywords
- Adhesive capsulitis
- Medical subject headings
- Bursitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Adalimumab InjectionDrug
40mg in 0.8ml preparation in vials from Fresenius Kabi Ltd
PlaceboDrug
Saline [0.9% NaCl]
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Active comparator | Participants will receive 2 injections of adalimumab. First injection: 160mg in 3.2ml Second injection approximately 2-3 weeks later 80mg in 1.6ml Receives: Drug: Adalimumab Injection |
| Arm B | Placebo comparator | Participants will receive 2 injections of placebo First injection: 3.2ml Second injection approximately 2-3 weeks later 1.6ml Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Eligible With Pain Predominant Frozen Shoulder
Ability to screen and identify potential participants with pain-predominant early stage frozen shoulder (i.e. within approximately 3 months of onset of symptoms).
Measured: 3 Months
Number of Participants Consenting to be Included in the Trial
Willingness of eligible participants to consent and be randomised to intervention.
Measured: 3 Months
Time From Randomisation to First Injection
Practicalities of delivering the intervention, including time to first injection (within 2 weeks of randomisation).
Measured: 2 weeks
Time From First Injection to Second Injection
Practicalities of delivering the intervention, including time between first injection and second injection (within 4-6 weeks of randomisation).
Measured: 6 weeks
Shoulder Pain and Disability Index (SPADI) Score
Score ranges from 0 to 100, lower scores indicate better outcome.
Measured: Baseline and 3 months
Secondary outcomes (10)
Pain (Shoulder Pain And Disability Index, 5-item Subscale)
Score ranges from 0 to 100, lower scores indicate better outcome.
Measured: Baseline and 3 months
Function (Shoulder Pain And Disability Index, 8-item Subscale)
Score ranges from 0 to 100, lower scores indicate better outcome.
Measured: Baseline and 3 months
Fear Avoidance Belief Questionnaire
Score ranges from 0 to 24, higher scores indicate better outcomes.
Measured: Baseline and 3 months
Pain Self Efficacy Questionnaire
Score ranges from 0 to 12, higher scores indicate better outcomes.
Measured: Baseline and 3 months
Insomnia Severity Index
Sleep disturbance measured using the Insomnia Severity Index, score ranges from 0 to 28, higher scores indicate worse outcomes.
Measured: Baseline and 3 months
Return to Desired Activities (RDA)
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.
Measured: Baseline and 3 months
Global Impression of Change
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.
Measured: 3 months
Health Resource Use
Consultation with primary and secondary care, additional physiotherapy, injection use, or alternative therapies for index shoulder
Measured: 3 months
Adverse Events Graded 3 or Above
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.
Measured: Consent to 3 months follow-up
Shoulder Range of Movement
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.
Measured: Baseline and 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2022
- Study start21 Jul 2022
- Primary completion9 May 2023
- Study completion12 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Frozen ShoulderStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Participants will be randomised to either receive Adalimumab or Placebo.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom, 180 Life Sciences
- Responsible party
- Sponsor
- Investigators
- Jagdeep Nanchahal, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05299242
- Sponsor's protocol ID
- 15701
- Acronym
- Anti-FreazeF
- Status last verified
- Nov 2022
- First submitted
- 17 Feb 2022
- Last updated
- 27 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Summary results data will be available on the trial registration database within 12 months of the end of the trial. Requests for data (anonymised participant data) will only be provided at the end of the trial to external researchers who provide a methodologically sound proposal to the trial team aff@kennedy.ox.ac.uk (will be required to sign a data sharing access agreement with the Sponsor) and in accordance with the NIHR guidance. Participant consent for this is included in the informed consent form for the study
Publications
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.
PubMed 37881307Hopewell S, Srikesavan C, Evans A, Er F, Rangan A, Preece J, Francis A, Massa MS, Feldmann M, Lamb S, Nanchahal J. Anti-TNF (adalimumab) injection for the treatment of pain-predominant early-stage frozen shoulder: the Anti-Freaze-Feasibility randomised controlled trial. BMJ Open. 2024 May 1;14(5):e078273. doi: 10.1136/bmjopen-2023-078273.
PubMed 38692727