The use of anakinra in treating complex regional pain syndrome by blocking interleukin-1
- Conditions
- Refractory complex regional pain syndromeNervous System DiseasesComplex regional pain syndrome
- Registration Number
- ISRCTN12908996
- Lead Sponsor
- niversity of Liverpool
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 26
Current inclusion criteria as of 30/01/2024 (updated 13/02/2024):
1. A diagnosis of CRPS I or II according to the Budapest research criteria at the time of the assessment for this study
2. First documented diagnosis of Budapest CRPS by a healthcare professional not less than 18 months and not longer than 15 years before the screening assessment. A valid documented diagnosis must either include the term 'Budapest CRPS', or must include the term 'CRPS' and in addition documentation of the presence of signs and symptoms which allow making the Budapest diagnosis from the notes.
3. Pain intensity average 6 or greater on a 0-10-point numerical rating scale (NRS) over a minimum of seven consecutive daily entries prior to baseline (0 day) visit, with no single value below 5.
4. Completed a previous course of appropriate specialised physiotherapy
5. Poor response or intolerance to at least one anti-neuropathic pain medication such as tricyclic antidepressants or gabapentinoids.
6. If a woman of childbearing potential (WOCBP), to be willing to confirm the use of adequate birth control during the trial period unless pregnancy is impossible
7. Fertile male patients to be using contraception for the duration of therapy if sexually active with a female partner.
8. Age 18 years and over
9. Written and informed consent obtained from patient and agreement of patient to comply with the requirements of the study
_____
Previous inclusion criteria as of 07/03/2023:
1. A diagnosis of CRPS I or II according to the Budapest research criteria at the time of the assessment for this study
2. First documented diagnosis of Budapest CRPS by a healthcare professional not longer than 15 years before the screening assessment. A valid documented diagnosis must either include the term 'Budapest CRPS', or must include the term 'CRPS' and in addition documentation of the presence of signs and symptoms which allow making the Budapest diagnosis from the notes.
3. Pain intensity average 6 or greater on a 0-10-point numerical rating scale (NRS) over a minimum of seven consecutive daily entries prior to baseline (0 day) visit, with no single value below 5.
4. Completed a previous course of appropriate specialised physiotherapy
5. Poor response to anti-neuropathic pain medications- either unacceptable side effects or inadequate pain relief (Clinicians discretion)
6. If a woman of childbearing potential (WOCBP), to be willing to confirm the use of adequate birth control during the trial period unless pregnancy is impossible
7. Fertile male patients to be using contraception for the duration of therapy if sexually active with a female partner
8. Age 18 years and over
9. Written and informed consent obtained from patient and agreement of patient to comply with the requirements of the study.
_____
Original inclusion criteria:
1. Diagnosis of complex regional pain syndrome I or II according to the Budapest research criteria
2. Disease duration of 18 months to 10 years
3. Average pain intensity of =6 on a 10-point numerical rating scale (NRS) over a minimum of 7 consecutive daily entries prior to baseline (0 day) visit, with no single value below
4. Completed a previous course of appropriate specialised physiotherapy
5. Poor response to anti-neuropathic pain medications- either unacceptable side effects or inadequate pain relief (Clinicians discretion)
6. If a woman of childbearing potential (WOCBP), to be willing to confirm the use of adequate birth control during the trial
Current exclusion criteria as of 30/01/2024 (updated 13/02/2024):
1. Medical conditions that in the opinion of the study investigator would make it unsafe for participation or can adversely affect outcomes
2. Co-existing pain that in the view of the study doctor may make assessment of outcomes related to refractory moderate to severe CRPS unreliable
3. Ongoing relevant litigation where its conclusion is imminent during the course of the study
4. Medical Contraindications to anakinra such as moderate/severe or progressive renal impairment (CLCR <60 ml/min or eGFR <60 ml/min/1.73m2 or end stage renal disease, including dialysis), or hepatic impairment (defined as any value of transaminases, ?-glutamyl transpeptidase, or bilirubin greater than
2 times the upper normal limit) or hypersensitivity to anakinra or any of its excipients or to E.coli-derived proteins.
5. Previous use of anakinra
6. Current or recent (within 6 months) use of other immunosuppressants or biologics
7. Neutropenia defined as Absolute Neutrophil Count< 1.5 x 109/L
8. Requirement to receive a live vaccine during the trial duration.
9. Active or latent Tuberculosis infection
10. HIV, Hepatitis B or C carrier
11. Brittle asthma
12. Active malignancy or malignancy within 2 years
13. Ongoing alcohol or drug misuse at registration
14. Psychiatric or other mental health disorder which in the opinion of the study investigator may interfere with successful study participation
15. Commencing new therapy for refractory moderate to severe CRPS that may alter the outcome of the trial drug; this includes new pain
management program treatment. Equally patients who have completed a pain management program within the past 3 months
16. Subject is pregnant or breastfeeding, inadequate birth control, or the possibility of pregnancy during the study.
17. Patients who have a spinal cord or dorsal root ganglion stimulator whose average pain is less than 6 out of 10 when the stimulator is on.
_____
Previous exclusion criteria as of 07/03/2023:
1. Medical conditions that, in the opinion of the study investigator, would make it unsafe for participation or can adversely affect outcomes
2. Co-existing pain that, in the view of the study doctor, may make an assessment of outcomes related to refractory moderate to severe CRPS unreliable
3. Ongoing relevant litigation where its conclusion is imminent during the course of the study
4. Medical Contraindications to anakinra such as moderate/severe or progressive renal impairment (eGFR<60ml/min/1.73m²), hepatic impairment (defined as any value of transaminases, ?-glutamyl transpeptidase, or bilirubin greater than 2 times the upper normal limit) or hypersensitivity to anakinra or any of its excipients or to E.coli-derived proteins.
5. Previous use of anakinra
6. Current or recent (within 6 months) use of other immunosuppressants or biologics
7. Neutropenia defined as Absolute Neutrophil Count <1.5 x 10e9/l
8. Requirement to receive a live vaccine during the trial duration
9. Active or latent tuberculosis infection
10. HIV, Hepatitis B or C carrier
11. Brittle asthma
12. Active malignancy or malignancy within 2 years
13. Ongoing alcohol or drug misuse at registration
14. Psychiatric or other mental health disorder which in the opinion of the study investigator may interfere with successful study participation
15. Commencing new therapy for refractory moderate to severe CRPS that may alter the outcome of the trial drug; this includes new pain managem
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1. Safety of anakinra assessed using the number of patients without serious adverse events at baseline (0 days) – 180 days<br>2. Tolerance of anakinra assessed using the proportion of patients without serious adverse events at baseline (0 days) – 180 days<br>3. Persistent pain at injection site assessed using pain numerical rating scale (NRS) at baseline (0 days) - 180 days<br>4. CRPS-associated pain assessed using CRPS Severity Score at baseline (0 days) - 120 days
- Secondary Outcome Measures
Name Time Method 1. Registration rate assessed using monitoring report monthly throughout the study<br>2. Pain intensity assessed using CRPS Severity Score at baseline (0 days) - 120 days<br>3. Overall status assessed using Global Impression of Change (PGIC) at 120 days<br>4. Functional/psychological improvement assessed using Patient Health Questionnaire (PHQ-9), Brief Pain Inventory (BPI), Hospital Anxiety and Depression Scale (HADS) at baseline (0 days) - 120 days<br>5. Quality of life assessed using EQ5-5D-5L at baseline (0 days) - 180 days<br>6. Skin and limb sensitivity assessed using mechanical Quantitative Sensory Testing (QST) at baseline (0 days) - 120 days<br>7. Limb volume assessed by figure of 8 measurements at screening, baseline (0 days), 60 and 120 days<br>8. Work status (working, returned to work, etc) recorded at baseline (0 days) and 120 days