Low-dose intravenous immunoglobulin treatment for Complex Regional Pain Syndrome
| ISRCTN | ISRCTN42179756 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN42179756 |
| EudraCT/CTIS number | 2012-000058-73 |
| Secondary identifying numbers | 12715 |
- Submission date
- 28/06/2013
- Registration date
- 28/06/2013
- Last edited
- 11/12/2018
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English summary of protocol
Background and study aims
Chronic pain is often defined as any pain lasting more than 12 weeks. Many patients with chronic pain do not experience satisfactory pain relief with currently available treatments. This may be related to the fact that the causes for chronic pain are often not fully understood. We have previously treated patients with intravenous immunoglobulin (IVIG), a mixture of antibodies delivered into a vein, and have reported encouraging results. It is now important to perform a larger study to explore this further.
Who can participate?
Patients aged over 18 with complex regional pain syndrome, a condition in which a person experiences persistent severe and debilitating pain.
What does the study involve?
Patients are randomly allocated to receive two infusions of either IVIG or placebo (dummy drug) 3 weeks apart and to complete detailed pain diaries. They also have the option to receive two further infusions of IVIG 3 weeks apart once the data for the study has been collected.
What are the possible benefits and risks of participating?
IVIG may provide pain relief in patients where classical treatments are not satisfactorily effective. If IVIG treatment proves to be effective, this study may also stimulate research on the use of IVIG in other chronic pain syndromes.
Where is the study run from?
King's College London (UK)
When is the study starting and how long is it expected to run for?
August 2013 to November 2015
Who is funding the study?
Biotest UK Ltd, NIHR and Pain Relief Foundation (UK)
Who is the main contact?
Caroline Murphy
caroline.murphy@kcl.ac.uk
Contact information
Scientific
16 De Crespigny Park
London
SE5 8AF
United Kingdom
| caroline.murphy@kcl.ac.uk |
Study information
| Study design | Double-blind randomised parallel placebo-controlled trial; Interventional; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | A multi-centre (UK) double-blind randomised parallel group placebo controlled trial to evaluate the efficacy, safety, and tolerability of Intravenous Immunoglobulin (IVIg) 0.5g/kg plus standard treatment, versus matched placebo plus standard treatment in patients with long standing Complex Regional Pain Syndrome |
| Study acronym | LIPS |
| Study objectives | Main objective of the trial: To gain, within 44 months, both definite proof of the clinical efficacy, and a more confident estimate of the effect size of low-dose IVIg treatment to reduce pain in patients with moderate or severe Complex Regional Pain Syndrome. Secondary objectives of the trial: To achieve better understanding of this technology, including: 1. Stability of effect with repeat administration 2. Factors predicting a beneficial response 3. Effects on additional outcome parameters including stimulus-evoked pain, pain interference, quality of life, and short-term risk profile 4. Health economics evaluation 5. Creation of a bank of biological samples for future CRPS research More details can be found at: http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=12715 |
| Ethics approval(s) | East of England Hatfield REC (formerly known as NRES Committee East of England Welwyn), 06/06/2013, ref:12/EE/0164 |
| Health condition(s) or problem(s) studied | Topic: Generic Health Relevance and Cross Cutting Themes; Subtopic: Generic Health Relevance (all Subtopics); Disease: Anaesthetics, Complex Regional Pain Syndrome |
| Intervention | The experimental intervention is 0.5 g/kg IntratectTM IVIg infusion, in combination with ongoing normal standard treatment for Complex Regional Pain Syndrome. |
| Intervention type | Other |
| Primary outcome measure | Added 26/01/2016: The average 24h pain intensity over 37 days, recorded in pain diary entries for the previous 24 hours collected on days 6 to 42 (day 1=day of first infusion) |
| Secondary outcome measures | Added 26/01/2016: 1. Pain interference measured using the interference subscale of the Brief Pain Inventory at days 22 and 43 2. Quality of life measured using the Euroqol EQ-5D-5L at days 22 and 43 All other outcomes are exploratory. |
| Overall study start date | 01/08/2013 |
| Completion date | 30/11/2015 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 108; UK Sample Size: 108 |
| Key inclusion criteria | 1. Diagnosis of CRPS I or II according to Budapest research criteria (appendix 3) (15). 2. Disease duration of 1-5 years and a mean pain intensity on an 11-point (0-10) Numeric Rating Scale (NRS) over the first seven daily entries after screening within a pre-defined range (see section 9 for details of pain thresholds for eligibility). 3. Failure to respond (poor efficacy or unacceptable side effects) to drugs recommended for the treatment of neuropathic pain (16), including pregabalin or gabapentin, a tricyclic antidepressant, and mild and strong opioids (where not contraindicated or refused by the patient). 4. Previous specialised pain physiotherapy (17), including desensitisation techniques, and either mirror therapy (18) or graded motor imagery treatment (19), or both (where not contraindicated or refused by the patient). 5. Willingness to confirm the use of adequate birth control while on the trial will be required in pre-menopausal women without evidence for an inability to become pregnant. 6. Willingness to not start any other treatment for CRPS during the parallel part of the trial. 7. Age 18 years and above; Target Gender: Male & Female |
| Key exclusion criteria | 1. Other significant chronic pains, which in the view of the study doctor may make assessment of the pain arising from CRPS difficult. 2. If the patient recently started a new therapy for CRPS, which in the view of the study doctor may change the patients pain level during the time of participation in the trial. 3. Unstable medical conditions. 4. Litigation. Patients in litigation will be excluded only if conclusion of that litigation is imminent during the course of the study. 5. Pregnant or breastfeeding patients. 6. Less than half of the lower limit of the normal serum IgA level given by the respective trials unit laboratory 7. Rare contraindications to IVIg therapy as per summary of product characteristics (SmPC) 8. Receiving IVIg for other reasons, 9. Patients previously enrolled in CRPS IVIg/SCIG trials 10. Drugs or alcohol abuse 11. Psychiatric or mental health disorder which could in the judgement of the site investigator interfere with successful study participation 12. Unwillingness or inability to complete daily diaries, or inability to understand the questionnaires being used. 13. Cancer other than basal cell carcinoma within the last 5 years. However, those patients who have received definitive treatment, such as curative surgery more than 6 months ago, with no known recurrence can be included. 14. A history of hypercoagulable or thrombophilic clotting abnormalities. 15. A history of thrombembolic events: ischaemic stroke, confirmed myocardial infarction, pulmonary embolism; deep venous thrombosis except where immobility related (e.g., after injury or operation). 16. Renal failure, or serum creatinine greater than 1.5 times the upper limit of normal at screening 17. Any medical condition which in the opinion of the investigator would make it unsafe for the patient to participate or which would interfere with assessment of the outcome measures. |
| Date of first enrolment | 15/08/2013 |
| Date of final enrolment | 28/10/2015 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
Study participating centres
L9 7LJ
United Kingdom
SE1 9RT
United Kingdom
CB2 0QQ
United Kingdom
NR4 7UY
United Kingdom
BA1 1RL
United Kingdom
G12 0YN
United Kingdom
LE3 9QP
United Kingdom
Sponsor information
University/education
c/o Karen Wilding
Thompson Yates Building
Quadrangle Brownlow Hill
Liverpool
L69 3GB
England
United Kingdom
| Website | http://www.liv.ac.uk/ |
|---|---|
"ROR" |
https://ror.org/04xs57h96 |
Funders
Funder type
Industry
No information available
No information available
Private sector organisation / Trusts, charities, foundations (both public and private)
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | To be confirmed at a later date |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 24/10/2014 | Yes | No | |
| Results article | results | 03/10/2017 | Yes | No | |
| Results article | results | 01/11/2017 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
11/12/2018: Publication references added.
08/07/2014: The following changes were made to the trial record:
1. The overall trial start date was changed from 01/10/2012 to 01/08/2013.
2. The overall trial end date was changed from 31/05/2014 to 30/11/2015.
