Intravenous Immunoglobulins in Complex-regional Pain Syndrome (PAINLESS)

Prospective, Double-blind, Randomised, Placebo-controlled, Cross-over Study to Investigate the Effect of Intravenous Immunoglobulins on Complex Regional Pain Syndrome (CRPS, M. Sudeck)

The purpose of this study is to determine whether intravenous immunoglobulins are effective in the treatment of complex-regional pain syndrome.

Study Overview

• Status: Withdrawn
• Conditions: Complex Regional Pain Syndrome Type 1
• Intervention / Treatment: Biological: intravenous immunoglobulins

Detailed Description

CRPS, a chronic pain syndrome associated with trophic disturbances is a frequent complication after limb trauma. More than one third of the CRPS will continue to chronic disease including loss of function in one limb. Some reports implicate an autoimmune pathogenesis of CRPS. Especially the finding of autoantibodies against peripheral neurons and successful treatment in single cases provide evidence for a possible successful treatment of CRPS with intravenous immunoglobulins (IvIg). Therefore IvIg may be an important anti-inflammatory treatment to prevent severe chronification of CRPS. Since IvIg is mainly effective in B-cell-mediated autoimmune diseases, autoantibodies against autonomic neurons and the concentration of B-cell activating factors BAFF and APRIL will be measured in the course of the study.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Hessen
    • Giessen, Hessen, Germany, 35392
      • Hospital of the Justus-Liebig-University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• CRPS 1 (according to the IASP criteria) between 6 weeks and 6 months after diagnosis
• skin temperature of the affected side equal or higher than on non-affected side
• no change of the analgetic or co-analgetic medication within the last 10 days

Exclusion Criteria:

• Immunosuppressive or immunomodulatory treatment within the last three months
• CRPS previously treated with sympathetic block, lidocaine patch, local DMSO, spinal cord stimulation, intrathecal drug administration
• Known immune-mediated neuropathy (CIDP, MMN, MADSAM)
• Selective IgA-deficiency
• Severe heart disease
• Tumour disease in the last 5 years
• Allergy against Gamunex 10%
• Chronic renal disease Vaccination with live vaccine within the last three months
• Member of another clinical trial within the last 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intravenous immunoglobulins (IvIg); 3 x 0.36-0.44g/Kg IvIg every 4 weeks, then 3 months washing out, then 3x NaCl 0.9% every 4 weeks	Biological: intravenous immunoglobulins; 0.36-0.44g/Kg IvIg intravenous, 3x, every 4 weeks; Other Names: Gamunex 10%
Placebo Comparator: NaCl 0.9%; NaCl 0.9%, 3x, every 4 weeks, then 3 months washing out, then 0.36-0.44g/Kg IvIg, 3x, every 4 weeks	Biological: intravenous immunoglobulins; 0.36-0.44g/Kg IvIg intravenous, 3x, every 4 weeks; Other Names: Gamunex 10%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in impairment Level SumScore (ISS)	after 0,3,6,9 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Pain disability score	0,3,6,9 months
Quality of life (SF-36)	0,3,6,9 months
Titer of surface-binding neuronal autoantibodies in the serum	0,3,6,9 months
Serum concentration of B-cell activating factors BAFF, APRIL	0,3,6,9 months

Collaborators and Investigators

• Sponsor: University of Giessen

Publications and helpful links

General Publications

• Kohr D, Tschernatsch M, Schmitz K, Singh P, Kaps M, Schafer KH, Diener M, Mathies J, Matz O, Kummer W, Maihofner C, Fritz T, Birklein F, Blaes F. Autoantibodies in complex regional pain syndrome bind to a differentiation-dependent neuronal surface autoantigen. Pain. 2009 Jun;143(3):246-251. doi: 10.1016/j.pain.2009.03.009. Epub 2009 Apr 16.
• Goebel A, Stock M, Deacon R, Sprotte G, Vincent A. Intravenous immunoglobulin response and evidence for pathogenic antibodies in a case of complex regional pain syndrome 1. Ann Neurol. 2005 Mar;57(3):463-4. doi: 10.1002/ana.20400. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2009
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): February 15, 2011

Study Registration Dates

• First Submitted: July 29, 2009
• First Submitted That Met QC Criteria: July 29, 2009
• First Posted (Estimate): July 30, 2009

Study Record Updates

• Last Update Posted (Actual): July 15, 2021
• Last Update Submitted That Met QC Criteria: July 8, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: autoimmune disease; complex regional pain syndrome; intravenous immunoglobulins; sympathetic reflex dystrophy
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Disease; Neuromuscular Diseases; Peripheral Nervous System Diseases; Autonomic Nervous System Diseases; Syndrome; Complex Regional Pain Syndromes; Reflex Sympathetic Dystrophy; Somatoform Disorders; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: 2007-007794-23