Trial Outcomes & Findings for The Anti-Freaze-F Study- "Anti-TNF for Treatment of Frozen Shoulder - a Feasibility Study" (NCT NCT05299242)

NCT ID: NCT05299242

Last Updated: 2025-01-27

Results Overview

Ability to screen and identify potential participants with pain-predominant early stage frozen shoulder (i.e. within approximately 3 months of onset of symptoms).

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 9 participants
• Primary outcome timeframe: 3 Months
• Results posted on: 2025-01-27

Participant Flow

Participant milestones

Measure	Adalimumab Participants received 2 injections of adalimumab. First injection: 160mg in 3.2ml. Second injection approximately 2-3 weeks later: 80mg in 1.6ml. Adalimumab Injection: 40mg in 0.8ml preparation in vials from Fresenius Kabi Ltd.	Placebo Participants received 2 injections of placebo. First injection: 3.2ml. Second injection approximately 2-3 weeks later: 1.6ml. Placebo: Saline \[0.9% NaCl\]
Overall Study STARTED	4	5
Overall Study COMPLETED	4	5
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

There were no participants in the Adalimumab group who were smokers, therefore the number of cigarettes smoked per day could not be collected for this group.

Baseline characteristics by cohort

Measure	Adalimumab n=4 Participants Participants received 2 injections of adalimumab. First injection: 160mg in 3.2ml. Second injection approximately 2-3 weeks later: 80mg in 1.6ml. Adalimumab Injection: 40mg in 0.8ml preparation in vials from Fresenius Kabi Ltd.	Placebo n=5 Participants Participants received 2 injections of placebo. First injection: 3.2ml. Second injection approximately 2-3 weeks later: 1.6ml. Placebo: Saline \[0.9% NaCl\]	Total n=9 Participants Total of all reporting groups
Age, Continuous	57.5 years STANDARD_DEVIATION 5.9 • n=4 Participants	52.8 years STANDARD_DEVIATION 5.0 • n=5 Participants	54.9 years STANDARD_DEVIATION 5.6 • n=9 Participants
Sex: Female, Male Female	1 Participants n=4 Participants	2 Participants n=5 Participants	3 Participants n=9 Participants
Sex: Female, Male Male	3 Participants n=4 Participants	3 Participants n=5 Participants	6 Participants n=9 Participants
Race/Ethnicity, Customized White British	4 Participants n=4 Participants	5 Participants n=5 Participants	9 Participants n=9 Participants
Region of Enrollment United Kingdom	4 Participants n=4 Participants	5 Participants n=5 Participants	9 Participants n=9 Participants
Handedness Left	2 Participants n=4 Participants	1 Participants n=5 Participants	3 Participants n=9 Participants
Handedness Right	2 Participants n=4 Participants	4 Participants n=5 Participants	6 Participants n=9 Participants
Duration of symptoms	19.5 weeks STANDARD_DEVIATION 13.1 • n=4 Participants	12.2 weeks STANDARD_DEVIATION 2.3 • n=5 Participants	15.4 weeks STANDARD_DEVIATION 9.0 • n=9 Participants
Smoking status Never smoked	4 Participants n=4 Participants	3 Participants n=5 Participants	7 Participants n=9 Participants
Smoking status Former smoker	0 Participants n=4 Participants	2 Participants n=5 Participants	2 Participants n=9 Participants
Dupuytren's disease No	4 Participants n=4 Participants	4 Participants n=5 Participants	8 Participants n=9 Participants
Dupuytren's disease Yes	0 Participants n=4 Participants	1 Participants n=5 Participants	1 Participants n=9 Participants
Diabetes Type 1	0 Participants n=4 Participants	1 Participants n=5 Participants	1 Participants n=9 Participants
Diabetes Type 2	1 Participants n=4 Participants	2 Participants n=5 Participants	3 Participants n=9 Participants
Diabetes No	3 Participants n=4 Participants	2 Participants n=5 Participants	5 Participants n=9 Participants
If ever smoked, number of cigarettes/day	—	12 cigarettes per day STANDARD_DEVIATION 11.3 • n=5 Participants • There were no participants in the Adalimumab group who were smokers, therefore the number of cigarettes smoked per day could not be collected for this group.	12 cigarettes per day STANDARD_DEVIATION 11.3 • n=5 Participants • There were no participants in the Adalimumab group who were smokers, therefore the number of cigarettes smoked per day could not be collected for this group.

PRIMARY outcome

Timeframe: 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).

Outcome measures

Measure	All Screened Participants n=156 Participants All participants who were screened for pain predominant frozen shoulder.	Placebo Participants received 2 injections of placebo. First injection: 3.2ml. Second injection approximately 2-3 weeks later: 1.6ml. Placebo: Saline \[0.9% NaCl\]
Number of Participants Eligible With Pain Predominant Frozen Shoulder	39 Participants	—

PRIMARY outcome

Timeframe: 3 Months

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

Outcome measures

Measure	All Screened Participants n=39 Participants All participants who were screened for pain predominant frozen shoulder.	Placebo Participants received 2 injections of placebo. First injection: 3.2ml. Second injection approximately 2-3 weeks later: 1.6ml. Placebo: Saline \[0.9% NaCl\]
Number of Participants Consenting to be Included in the Trial	9 Participants	—

PRIMARY outcome

Timeframe: 2 weeks

Population: All participants received their treatment as allocated and in line with the trial protocol. One participant in the adalimumab group received their injection 18 days post- randomisation as they were not available until then.

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

Outcome measures

Measure	All Screened Participants n=4 Participants All participants who were screened for pain predominant frozen shoulder.	Placebo n=5 Participants Participants received 2 injections of placebo. First injection: 3.2ml. Second injection approximately 2-3 weeks later: 1.6ml. Placebo: Saline \[0.9% NaCl\]
Time From Randomisation to First Injection	12.3 days Standard Deviation 4.8	7.2 days Standard Deviation 4.1

PRIMARY outcome

Timeframe: 6 weeks

Population: All participants received their treatment as allocated and in line with the trial protocol.

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

Outcome measures

Measure	All Screened Participants n=4 Participants All participants who were screened for pain predominant frozen shoulder.	Placebo n=5 Participants Participants received 2 injections of placebo. First injection: 3.2ml. Second injection approximately 2-3 weeks later: 1.6ml. Placebo: Saline \[0.9% NaCl\]
Time From First Injection to Second Injection	18.5 days Standard Deviation 3.3	20.8 days Standard Deviation 5.9

PRIMARY outcome

Timeframe: Baseline and 3 months

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

Outcome measures

Measure	All Screened Participants n=4 Participants All participants who were screened for pain predominant frozen shoulder.	Placebo n=5 Participants Participants received 2 injections of placebo. First injection: 3.2ml. Second injection approximately 2-3 weeks later: 1.6ml. Placebo: Saline \[0.9% NaCl\]
Shoulder Pain and Disability Index (SPADI) Score Baseline	70.8 score on a scale Standard Deviation 16.6	55.4 score on a scale Standard Deviation 21.5
Shoulder Pain and Disability Index (SPADI) Score 3 months	40.1 score on a scale Standard Deviation 30.0	45.8 score on a scale Standard Deviation 25.3

SECONDARY outcome

Timeframe: Baseline and 3 months

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

Outcome measures

Measure	All Screened Participants n=4 Participants All participants who were screened for pain predominant frozen shoulder.	Placebo n=5 Participants Participants received 2 injections of placebo. First injection: 3.2ml. Second injection approximately 2-3 weeks later: 1.6ml. Placebo: Saline \[0.9% NaCl\]
Pain (Shoulder Pain And Disability Index, 5-item Subscale) Baseline	78.5 score on a scale Standard Deviation 18.4	63.2 score on a scale Standard Deviation 19.5
Pain (Shoulder Pain And Disability Index, 5-item Subscale) 3 months	41.5 score on a scale Standard Deviation 32.7	49.6 score on a scale Standard Deviation 27.3

SECONDARY outcome

Timeframe: Baseline and 3 months

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

Outcome measures

Measure	All Screened Participants n=4 Participants All participants who were screened for pain predominant frozen shoulder.	Placebo n=5 Participants Participants received 2 injections of placebo. First injection: 3.2ml. Second injection approximately 2-3 weeks later: 1.6ml. Placebo: Saline \[0.9% NaCl\]
Function (Shoulder Pain And Disability Index, 8-item Subscale) Baseline	63.1 score on a scale Standard Deviation 15.6	47.5 score on a scale Standard Deviation 25.7
Function (Shoulder Pain And Disability Index, 8-item Subscale) 3 months	38.8 score on a scale Standard Deviation 30.3	42.0 score on a scale Standard Deviation 24.7

SECONDARY outcome

Timeframe: Baseline and 3 months

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

Outcome measures

Measure	All Screened Participants n=4 Participants All participants who were screened for pain predominant frozen shoulder.	Placebo n=5 Participants Participants received 2 injections of placebo. First injection: 3.2ml. Second injection approximately 2-3 weeks later: 1.6ml. Placebo: Saline \[0.9% NaCl\]
Fear Avoidance Belief Questionnaire Baseline	17.3 score on a scale Standard Deviation 3.3	17.4 score on a scale Standard Deviation 3.6
Fear Avoidance Belief Questionnaire 3 months	9.3 score on a scale Standard Deviation 6.2	12.8 score on a scale Standard Deviation 5.9

SECONDARY outcome

Timeframe: Baseline and 3 months

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

Outcome measures

Measure	All Screened Participants n=4 Participants All participants who were screened for pain predominant frozen shoulder.	Placebo n=5 Participants Participants received 2 injections of placebo. First injection: 3.2ml. Second injection approximately 2-3 weeks later: 1.6ml. Placebo: Saline \[0.9% NaCl\]
Pain Self Efficacy Questionnaire Baseline	9 score on a scale Standard Deviation 3.6	9.2 score on a scale Standard Deviation 1.9
Pain Self Efficacy Questionnaire 3 months	10.5 score on a scale Standard Deviation 1.3	8.2 score on a scale Standard Deviation 2.8

SECONDARY outcome

Timeframe: Baseline and 3 months

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

Outcome measures

Measure	All Screened Participants n=4 Participants All participants who were screened for pain predominant frozen shoulder.	Placebo n=5 Participants Participants received 2 injections of placebo. First injection: 3.2ml. Second injection approximately 2-3 weeks later: 1.6ml. Placebo: Saline \[0.9% NaCl\]
Insomnia Severity Index Baseline	17.8 score on a scale Standard Deviation 5.0	17.6 score on a scale Standard Deviation 4.0
Insomnia Severity Index 3 months	9.8 score on a scale Standard Deviation 6.7	13.2 score on a scale Standard Deviation 7.6

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	All Screened Participants n=4 Participants All participants who were screened for pain predominant frozen shoulder.	Placebo n=5 Participants Participants received 2 injections of placebo. First injection: 3.2ml. Second injection approximately 2-3 weeks later: 1.6ml. Placebo: Saline \[0.9% NaCl\]
Return to Desired Activities (RDA) Baseline	9.0 score on a scale Standard Deviation 4.5	9.4 score on a scale Standard Deviation 2.7
Return to Desired Activities (RDA) 3 month	5.5 score on a scale Standard Deviation 3.8	8.4 score on a scale Standard Deviation 3.6

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	All Screened Participants n=4 Participants All participants who were screened for pain predominant frozen shoulder.	Placebo n=5 Participants Participants received 2 injections of placebo. First injection: 3.2ml. Second injection approximately 2-3 weeks later: 1.6ml. Placebo: Saline \[0.9% NaCl\]
Global Impression of Change	2.3 score on a scale Standard Deviation 2.2	0.0 score on a scale Standard Deviation 3.0

SECONDARY outcome

Timeframe: 3 months

Consultation with primary and secondary care, additional physiotherapy, injection use, or alternative therapies for index shoulder

Outcome measures

Measure	All Screened Participants n=4 Participants All participants who were screened for pain predominant frozen shoulder.	Placebo n=5 Participants Participants received 2 injections of placebo. First injection: 3.2ml. Second injection approximately 2-3 weeks later: 1.6ml. Placebo: Saline \[0.9% NaCl\]
Health Resource Use Steroid injection (injection outside of the trial) · Yes	1 Participants	0 Participants
Health Resource Use Steroid injection (injection outside of the trial) · No	3 Participants	5 Participants
Health Resource Use NHS community-based services (physiotherapist) · Yes	1 Participants	0 Participants
Health Resource Use NHS community-based services (physiotherapist) · No	3 Participants	5 Participants
Health Resource Use Hospital as NHS outpatient (physiotheraphy department) · Yes	2 Participants	0 Participants
Health Resource Use Hospital as NHS outpatient (physiotheraphy department) · No	2 Participants	5 Participants
Health Resource Use Admitted as an inpatient · Yes	0 Participants	0 Participants
Health Resource Use Admitted as an inpatient · No	4 Participants	5 Participants
Health Resource Use Had surgery · Yes	0 Participants	0 Participants
Health Resource Use Had surgery · No	4 Participants	5 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	All Screened Participants n=4 Participants All participants who were screened for pain predominant frozen shoulder.	Placebo n=5 Participants Participants received 2 injections of placebo. First injection: 3.2ml. Second injection approximately 2-3 weeks later: 1.6ml. Placebo: Saline \[0.9% NaCl\]
Adverse Events Graded 3 or Above	0 Adverse events graded 3 or above	0 Adverse events graded 3 or above

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	All Screened Participants n=4 Participants All participants who were screened for pain predominant frozen shoulder.	Placebo n=5 Participants Participants received 2 injections of placebo. First injection: 3.2ml. Second injection approximately 2-3 weeks later: 1.6ml. Placebo: Saline \[0.9% NaCl\]
Shoulder Range of Movement Baseline flexion	71.3 degrees Standard Deviation 26.3	101.6 degrees Standard Deviation 24.7
Shoulder Range of Movement 3-month flexion	112.5 degrees Standard Deviation 54.8	140.0 degrees Standard Deviation 25.7
Shoulder Range of Movement Baseline extension	26.3 degrees Standard Deviation 18.0	27.6 degrees Standard Deviation 9.5
Shoulder Range of Movement 3-month extension	30.0 degrees Standard Deviation 8.2	40.6 degrees Standard Deviation 9.8
Shoulder Range of Movement Baseline abduction	50.0 degrees Standard Deviation 30.3	69.0 degrees Standard Deviation 26.6
Shoulder Range of Movement 3-month abduction	105.0 degrees Standard Deviation 56.1	115.0 degrees Standard Deviation 42.7
Shoulder Range of Movement Baseline internal rotation	23.8 degrees Standard Deviation 18.9	40.2 degrees Standard Deviation 40.8
Shoulder Range of Movement 3-month internal rotation	21.3 degrees Standard Deviation 17.0	41.0 degrees Standard Deviation 37.8
Shoulder Range of Movement Baseline external rotation	22.5 degrees Standard Deviation 8.7	15.0 degrees Standard Deviation 16.9
Shoulder Range of Movement 3-month external rotation	28.8 degrees Standard Deviation 6.3	55.0 degrees Standard Deviation 16.2

Adverse Events

Adalimumab

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Prof. Sally Hopewell

University of Oxford

Phone: +441865223458

Email: sally.hopewell@csm.ox.ac.uk

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place