Intravenous Immunoglobulin (IVIG) for Resistant Neuropathic Pain

IVIG for Treatment of Resistant Neuropathic Pain: a Preliminary Study

This project addresses a vexing problem that has alluded the best efforts of the medical/scientific community: treatment of resistant neuropathic pain. Neuropathic pain is common and includes conditions such as diabetic neuropathy, post herpetic neuralgia and post stroke pain and is believed to affect at least 3% of adults. Surveys of patients with neuropathic pain indicate that 60% do not receive adequate relief with current treatment. Results from recent laboratory and human studies reveal a new approach to treatment. This approach is based on the findings that neuroinflammation appears to be involved in development and maintenance of neuropathic pain. This study explores the effects of an immune-modulating blood-derived product, intravenous immunoglobulin (IVIG), in treating neuropathic pain. IVIG is thought to reduce neuroinflammation contributing to neuropathic pain. If successful, the study will provide important insights into pain mechanisms and a better understanding of how IVIG relieves neuropathic pain.

Hypotheses:

1. Reduction in neuroinflammation (NI) markers will co-vary with clinical indicators of pain relief
2. Patients with higher levels of markers of NI will be more likely to respond to IVIG

Study Overview

• Status: Unknown
• Conditions: Neuropathic Pain
• Intervention / Treatment: Biological: Intravenous immunoglobulin; Biological: Normal Saline

Detailed Description

This study will employ a randomized double blind cross-over design. A total of 12 subjects will be recruited for the study. Once each subject has satisfied the inclusion and exclusion criteria and provided informed consent, the subject will be randomized to either the IVIG or placebo treatment groups, using a pre-determined randomization list generated by the research office at the University of Calgary. Complete responders will begin a monitoring phase, partial and non-responders will return for a second cycle in one month. Complete responders, with prolonged relief, will cross-over to the alternative treatment when their pain returns if this occurs within 6 months of the infusion.

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Recruiting
      • Foothills Medical Centre
      • Contact: Alexander J Clark, MD; Phone Number: 403 943 9917
      • Contact: Patricia Muehler; Phone Number: 403 943 9917
      • Principal Investigator: Alexander J Clark, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age >18 years; Clinical diagnosis of treatment-resistant neuropathic pain;
• Score of 4/10 or greater on the DN4 NeP screening questionnaire;
• Bedside examination confirming symptoms of neuropathic pain;
• Moderate to severe pain;
• Completed adequate analgesic trials according to neuropathic pain clinical practice guidelines;
• provides informed consent

Exclusion Criteria:

• Pregnant or lactating women;
• Clinical diagnosis of phantom limb pain;
• History of psychosis;
• current, substance dependency disorder;
• presence of clinically significant cardiac or pulmonary disorder that would compromise participants' safety;
• severe pain disorder other than the chronic NeP under study;
• Abnormalities above 1.5 times upper range of normal on screening CBC, blood chemistry;
• Serum IgA less than <0.05 g/L

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IVIG; Active treatment will be intravenous immunoglobulin G (Gamunex, immune globulin intravenous [human], 10%), at a dose of 2 g/kg divided over five days (0.4 g/kg/day).	Biological: Intravenous immunoglobulin; 2 g/kg divided over five days
Placebo Comparator: Placebo; The placebo treatment will be intravenous normal saline and will be infused in a similar manner.	Biological: Normal Saline; Same volume as experimental arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary outcome measure will consist of change in mean daily pain diary score from baseline to each week post-treatment	Performed at screening, before the initial infusion, 2 weeks and 4 weeks post treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Measurement of neuroinflammation (NI) markers (IL-1β, IL-6, IL-8, TNF-α, MMP-9, TIMP-1)	Performed at screening, before the initial infusion, 2 weeks and 4 weeks post treatment

Collaborators and Investigators

• Sponsor: University of Calgary
• Investigators: Principal Investigator: Alexander J Clark, MD, FRCPC, University Of Calgary

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Anticipated): July 1, 2010
• Study Completion (Anticipated): December 1, 2010

Study Registration Dates

• First Submitted: February 18, 2009
• First Submitted That Met QC Criteria: February 23, 2009
• First Posted (Estimate): February 24, 2009

Study Record Updates

• Last Update Posted (Estimate): February 24, 2009
• Last Update Submitted That Met QC Criteria: February 23, 2009
• Last Verified: February 1, 2009

More Information

Terms related to this study

• Keywords: neuropathic pain; resistant; neuroinflammation; neuroinflammatory markers; Neuropathic pain that has not responded to standard therapy
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: 200434