Intravenous immunoglobulin in the treatment of primary trigeminal neuralgia refractory to carbamazepine: a study protocol[ISRCTN33042138]

Andreas Goebel¹^,2 , Andrew Moore¹ , Rosamund Weatherall³ , Norbert Roewer² , Robert Schedel² and Guenter Sprotte²

¹Nuffield Department of Anaesthetics, University of Oxford, Oxford Ox3 9DU, England, UK

²Klinik für Anaesthesiologie, Julius Maximillians Universität Würzburg, 97080 Würzburg, Germany

³Center for Statistics in Medicine, University of Oxford, Oxford OX3 7LF, England, UK

author email corresponding author email

BMC Neurology 2003, 3:1doi:10.1186/1471-2377-3-1


Published:	30 January 2003

Abstract

Background

We have recently reported successful treatment of patients with chronic pain syndromes using human pooled intravenous immunoglobulin (IVIG) in a prospective, open-label cohort study. A randomised, placebo controlled, double blinded study is needed to confirm these results. We chose to study patients with carbamazepine resistant primary Trigeminal Neuralgia (rpTN), as these had responded particularly well to IVIG.

A protocol involving the use of IVIG in rpTN is complex for three reasons: 1. The effect of IVIG does not follow simple dose-response rules; 2. The response pattern of patients to IVIG was variable and ranged between no effect at all and pain free remission between two weeks and >1 year; 3. TN is characterized by extremely severe pain, for which operative intervention is (if temporarily) helpful in most patients.

Design

A placebo controlled, parallel, add-on model was developed and the primary outcome variable defined as the length of time during which patients remain in the study. Study groups are compared using Kaplan-Maier survival analysis. Patients record their response to treatment ("severe, moderate, slight, no pain"). The study coordinator monitors pain diaries. Severe or moderate pain of three days duration will result in termination of the study for that patient.

Conclusions

This study design utilizes a method of survival analysis and is novel in chronic pain research. It allows for both early departure from the study and voluntary crossover upon non-response. It may be applicable to the analysis of IVIG efficacy in other chronic pain syndromes.