NCT05299242: Anti-FreazeF

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

Completed Phase 2, PHASE3 Results posted Last updated 27 January 2025

What this trial tests

Phase 2, PHASE3 trial testing Adalimumab Injection in Frozen Shoulder in 9 participants. Completed in 12 June 2023.

Timeline

21 July 2022

Primary endpoint
9 May 2023

12 June 2023

Quick facts

Lead sponsor	University of Oxford
Phase	Phase 2, PHASE3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	sequential
Masking	triple
Primary purpose	treatment
Enrollment	9
Start date	21 July 2022
Primary completion	9 May 2023
Estimated completion	12 June 2023
Sites	4 locations across United Kingdom

Drugs / interventions tested

• Adalimumab Injection
• Placebo

Conditions studied

• Frozen Shoulder — all drugs for Frozen Shoulder →

Sponsor

University of Oxford

Who can join

18 and older, any sex, with Frozen Shoulder. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Eligible With Pain Predominant Frozen Shoulder Primary · 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).

Group	Value	95% CI
All Screened Participants	39

Number of Participants Consenting to be Included in the Trial Primary · 3 Months

Willingness of eligible participants to consent and be randomised to intervention.

Group	Value	95% CI
Eligible Participants	9

Time From Randomisation to First Injection Primary · 2 weeks

Practicalities of delivering the intervention, including time to first injection (within 2 weeks of randomisation).

Group	Value	95% CI
Adalimumab	12.3	± 4.8
Placebo	7.2	± 4.1

Time From First Injection to Second Injection Primary · 6 weeks

Practicalities of delivering the intervention, including time between first injection and second injection (within 4-6 weeks of randomisation).

Group	Value	95% CI
Adalimumab	18.5	± 3.3
Placebo	20.8	± 5.9

Shoulder Pain and Disability Index (SPADI) Score Primary · Baseline and 3 months

Score ranges from 0 to 100, lower scores indicate better outcome.

Baseline

Group	Value	95% CI
Adalimumab	70.8	± 16.6
Placebo	55.4	± 21.5

3 months

Group	Value	95% CI
Adalimumab	40.1	± 30.0
Placebo	45.8	± 25.3

Pain (Shoulder Pain And Disability Index, 5-item Subscale) Secondary · Baseline and 3 months

Score ranges from 0 to 100, lower scores indicate better outcome.

Baseline

Group	Value	95% CI
Adalimumab	78.5	± 18.4
Placebo	63.2	± 19.5

3 months

Group	Value	95% CI
Adalimumab	41.5	± 32.7
Placebo	49.6	± 27.3

Function (Shoulder Pain And Disability Index, 8-item Subscale) Secondary · Baseline and 3 months

Score ranges from 0 to 100, lower scores indicate better outcome.

Baseline

Group	Value	95% CI
Adalimumab	63.1	± 15.6
Placebo	47.5	± 25.7

3 months

Group	Value	95% CI
Adalimumab	38.8	± 30.3
Placebo	42.0	± 24.7

Fear Avoidance Belief Questionnaire Secondary · Baseline and 3 months

Score ranges from 0 to 24, higher scores indicate better outcomes.

Baseline

Group	Value	95% CI
Adalimumab	17.3	± 3.3
Placebo	17.4	± 3.6

3 months

Group	Value	95% CI
Adalimumab	9.3	± 6.2
Placebo	12.8	± 5.9

Pain Self Efficacy Questionnaire Secondary · Baseline and 3 months

Score ranges from 0 to 12, higher scores indicate better outcomes.

Baseline

Group	Value	95% CI
Adalimumab	9	± 3.6
Placebo	9.2	± 1.9

3 months

Group	Value	95% CI
Adalimumab	10.5	± 1.3
Placebo	8.2	± 2.8

Insomnia Severity Index Secondary · Baseline and 3 months

Sleep disturbance measured using the Insomnia Severity Index, score ranges from 0 to 28, higher scores indicate worse outcomes.

Baseline

Group	Value	95% CI
Adalimumab	17.8	± 5.0
Placebo	17.6	± 4.0

3 months

Group	Value	95% CI
Adalimumab	9.8	± 6.7
Placebo	13.2	± 7.6

Return to Desired Activities (RDA) Secondary · 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.

Baseline

Group	Value	95% CI
Adalimumab	9.0	± 4.5
Placebo	9.4	± 2.7

3 month

Group	Value	95% CI
Adalimumab	5.5	± 3.8
Placebo	8.4	± 3.6

Global Impression of Change Secondary · 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.

Group	Value	95% CI
Adalimumab	2.3	± 2.2
Placebo	0.0	± 3.0

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Anti-TNF (adalimumab) injection for the treatment of pain-predominant early-stage frozen shoulder: the Anti-Freaze-Feasibility randomised controlled trial.
   Hopewell S, Srikesavan C, Evans A, Er F, et al · · 2024 · cited 4× · PMID 38692727 · DOI 10.1136/bmjopen-2023-078273
2. 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.
   Hopewell S, Kenealy N, Knight R, Rangan A, et al · · 2022 · cited 4× · PMID 37881307 · DOI 10.3310/nihropenres.13275.2
3. 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
   Hopewell S, Kenealy N, Knight R, Rangan A, et al · · 2023 · DOI 10.3310/nihropenres.13275.2