Condition category
Nervous System Diseases
Date applied
28/06/2013
Date assigned
28/06/2013
Last edited
28/01/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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
-
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 patient’s 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

http://www.liv.ac.uk/

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

  1. 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.

Additional files

Editorial Notes

On 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.