Journal of Clinical Trials
Open Access

Abstract

Methods for an International Randomized Clinical Trial to Investigate the Effect of Gsk249320 on Motor Cortex Neurophysiology using Transcranial Magnetic Stimulation in Survivors of Stroke

Matt P. Malcolm, Lori Enney and Steven C Cramer

Introduction: Transcranial Magnetic Stimulation (TMS) is a neurophysiological tool capable of assessing the motor nervous system and its change over time. In multi-site clinical trials, this technique has some advantages over other neuroimaging methods owing to its relatively low cost, low personnel and equipment infrastructure requirements, and greater ease in consistently applying technology to collect and analyze data. Limited published details exist regarding methods to deliver TMS and analyze data in a standardized and consistent manner as part of an international, multicenter, clinical trial.
Purpose: The objective of this paper is to describe standardized methods of applying TMS motor cortex assessments in an international clinical trial of a pharmacological intervention for stroke patients, which was conducted at 15 centers in three countries.
Materials and methods: A standardization process was developed to ensure TMS protocol adherence and data quality, and each clinical site was required to successfully complete standardization procedures prior to collecting patient data. Key elements of standardization included internet-based training, pilot subject data collection, common TMS equipment across sites, and corrective feedback provided by a standardization administrator. Subsequently, TMS assessments of motor hot spot location, motor threshold, and recruitment curve were conducted in stroke patients on post-stroke Days 5, 30, and 112. Ongoing standardization was maintained by regular review of patient data and communication between the clinical site and standardization administrator.
Conclusion: Although TMS methodological approaches vary, a protocol with standardized procedures was successfully developed and implemented. Using this protocol, centers were formally certified to perform TMS-based neurophysiological measures in this clinical trial of stroke patients. The methodology described is potentially valuable to investigators who might construct future multi-site clinical trials using TMS.