Plain English Summary
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
Trial website
Contact information
Type
Scientific
Primary contact
Ms Caroline Murphy
ORCID ID
Contact details
16 De Crespigny Park
London
SE5 8AF
United Kingdom
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caroline.murphy@kcl.ac.uk
Additional identifiers
EudraCT number
2012-000058-73
ClinicalTrials.gov number
Protocol/serial number
12715
Study information
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
Acronym
LIPS
Study hypothesis
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
East of England Hatfield REC (formerly known as NRES Committee East of England Welwyn), 06/06/2013, ref:12/EE/0164
Study design
Double-blind randomised parallel placebo-controlled trial; Interventional; Design type: Treatment
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
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
Phase
Not Applicable
Drug names
Primary outcome measures
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 trial start date
01/08/2013
Overall trial end date
30/11/2015
Reason abandoned
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 108; UK Sample Size: 108
Participant 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.
Recruitment start date
15/08/2013
Recruitment end date
28/10/2015
Locations
Countries of recruitment
United Kingdom
Trial participating centre
The Walton Centre NHS Trust
Liverpool
L9 7LJ
United Kingdom
Trial participating centre
Guy's and St Thomas' Hospital
London
SE1 9RT
United Kingdom
Trial participating centre
Addenbrooke's Hospital
Cambridge
CB2 0QQ
United Kingdom
Trial participating centre
Norfolk and Norwich University Hospital
Norwich
NR4 7UY
United Kingdom
Trial participating centre
Royal National Hospital for Rheumatic Diseases
Bath
BA1 1RL
United Kingdom
Trial participating centre
Gartnavel General Hospital
Glasgow
G12 0YN
United Kingdom
Trial participating centre
University Hospitals of Leicester
Leicester
LE3 9QP
United Kingdom
Sponsor information
Organisation
University of Liverpool (UK)
Sponsor details
c/o Karen Wilding
Thompson Yates Building
Quadrangle Brownlow Hill
Liverpool
L69 3GB
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Government
Funder name
Biotest UK Ltd
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
NIHR (UK) - Efficacy and Mechanism Evaluation; Grant Codes: 11/14/33
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Pain Relief Foundation (UK)
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
foundation
Location
United Kingdom
Results and Publications
Publication and dissemination plan
To be confirmed at a later date
Intention to publish date
Participant level data
Not expected to be available
Results - basic reporting
Publication summary
2014 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/25344328
Publication citations
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Protocol
Goebel A, Shenker N, Padfield N, Shoukrey K, McCabe C, Serpell M, Sanders M, Murphy C, Ejibe A, Milligan H, Kelly J, Ambler G, Low-dose intravenous immunoglobulin treatment for complex regional pain syndrome (LIPS): study protocol for a randomized controlled trial., Trials, 2014, 15, 1, 404, doi: 10.1186/1745-6215-15-404.