Spinal Direct Current Stimulation Effects on Pain in Multiple Sclerosis

January 5, 2015 updated by: IRCCS National Neurological Institute "C. Mondino" Foundation

Spinal Direct Current Stimulation Effects on Pain in Multiple Sclerosis: Clinical and Neurophysiological Assessment and Evaluation of Endocannabinoid System Activity

Pain represents one of the most common symptoms of Multiple Sclerosis (MS) that can seriously affect patient health-related quality of life.

Central neuropathic pain, the main form of pain in MS patients, represents a significant clinical problem, in consideration of its poorly responsiveness to available therapies.

Direct Current Stimulation (tDCS) is a non-invasive, well-tolerated procedure with an high and well documented neuromodulation activity at Central Nervous System (CNS) level. First evidences obtained by animal, neurophysiological and clinical studies suggested its potential efficacy in neuropathic pain treatment.

In particular spinal DCS (sDCS) has been proven to modulate Nociceptive Withdrawal Reflex (NWR), an objective and sensitive tool to explore pain processing at the Spinal Level and recommended by European Federation of Neurological Society (EFNS) to evaluate the analgesic effect of treatments. In this order of view the investigators' objective is to investigate sDCS efficacy in MS neurophatic pain treatment applying validated clinical scales, neurophysiological acquisitions and specific biological marker dosages.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

The investigators plan to recruit, at the IRCCS Neurological National Institute C. Mondino, 60 consecutive patients with definite Multiple Sclerosis (MS) according to 2005 McDonald criteria in a follow-up procedure that includes a general and neurological evaluation scored according to the Expanded Disability Status Scale of Kurtzke and its functional systems.

Relapsing-remitting (RR), secondary-progressive (SP) and primary-progressive (PP) MS patients, affecting by neuropathic or nociceptive chronic pain conditions in accord to 1994 International Association for the Study of Pain (IASP)classification, will be recruited. Patients complaining any form of headache will be excluded by the study. The investigators will excluded also patients with cognitive impairment (Minimental State Examination - MMSE- <= 21) and psychiatry diseases, in particular depression (Back Depression Inventory Scale - BDI - >15).

Characteristic and intensity of pain symptoms will be collected respectively with validated Italian version of Neuropathic Pain Symptoms Inventory Scale (NPSI) and Numerical Rating Scale (NRS). Spasticity of lower legs, if present, will be clinical assessed with Ashworth Scale and Neurophysiologically evaluated with H/M ratio and Vibratory Inhibition of H-Reflex.

Health-Related Quality of Life (HRQoL) will be assessed by means of the Medical Outcome 36-item Short Form Health Survey (SF-36) whereas the presence and severity of fatigue will be assessed by means of the Fatigue Severity Scale (FSS).

RR patients will be evaluated in stationary phase of the disease that is at least two months after the last clinical relapse and at least one month after the end of a steroidal treatment.

Patients will be consecutive enrolled in the study and randomly assigned to two group: 1. Sham and 2. Anodal Spinal Direct Current Stimulation Treatment, in a double-blind, placebo controlled study design.

Before enrollment, the study protocol will be explained to each subject, and informed written consent will be obtained.

The investigators will proceed as follow:

  1. Time of enrollment - T0 First Day

    • Complete clinical evaluation with administration of MMSE and BDI for exclusion criteria
    • Randomized assignment to Anodal or Sham treatment group
    • Administration of NPSI, SF-36, HRQoL e FSS
    • Evaluation of Somatosensory Evoked Potential by Posterior Tibial and Medial Nerve stimulation to investigate the somatosensory pathway involvement.
    • Clinical and Neurophysiological evaluation of Spasticity (if present): Ashworth Scale and H/M ratio and HReflex Vibratory Inhibition.
    • Collection of blood sample to evaluate activity of Fatty Acid Amide Hydrolase (FAAH) in platelets.

    Second Day

    • First Anodal or Sham Direct Current Stimulation Treatment Session (sDCS)
    • Neurophysiological acquisition of Nociceptive Withdrawal Reflex (NWR) and NWR Temporal Summation (see 'Neurophysiological Acquisition' Session for details) before and after 30 and 60 minutes the first sDCS treatment
  2. sDCS Treatment After evaluation at T0 patients will undergo 10 daily sDCS treatment, 5 days a week (see sDCS treatment session for details).

  3. Evaluation after 10 days of treatment - T1

    • Administration of NPSI, SF-36, HRQoL e FESS
    • Clinical and Neurophysiological evaluation of Spasticity (if present): Ashworth Scale and H/M ratio and HReflex Vibratory Inhibition.
    • Collection of blood sample to evaluate activity of Fatty Acid Amide Hydrolase (FAAH) in platelets.
    • Neurophysiological acquisition of Nociceptive Withdrawal Reflex (NWR) and NWR Temporal Summation

  4. Evaluation after 1 month from the end of treatment - T2

    • Administration of NPSI, SF-36, HRQoL e FESS
    • Clinical and Neurophysiological evaluation of Spasticity (if present): Ashworth Scale and H/M ratio and HReflex Vibratory Inhibition.
    • Collection of blood sample to evaluate activity of Fatty Acid Amide Hydrolase (FAAH) in platelets.
    • Neurophysiological acquisition of Nociceptive Withdrawal Reflex (NWR) and NWR Temporal Summation

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Pavia, Italy, 27100
        • Recruiting
        • IRCCS Fondazione Istituto Neurologico Nazionale C. Mondino
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Relapsing-remitting (RR), secondary-progressive (SP) and primary-progressive (PP) MS patients, affected by neuropathic or nociceptive chronic pain conditions in accordance to 1994 IASP (International Association for the Study of Pain) classification

Exclusion Criteria:

  • Any form of headache
  • Cognitive impairment (Minimental State Examination <= 21)
  • Psychiatry diseases, in particular depression (Back Depression Inventory Scale >15)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental Treatment
Anodal DC stimulation (2 mA, 20 min) will be delivered by a constant direct current electrical stimulator connected to a pair of electrodes: the anode will be placed on the thoracic spinal cord (over the spinal process of the tenth thoracic vertebra) and the cathode (reference) above the right shoulder. Stimulating electrodes will be thick (6 mm), rectangular pieces of saline-soaked synthetic sponge. The sDCS polarity (anodal) will refer to the electrode over the spinal cord.
Other: Experimental treatment
Anodal DC stimulation (2 mA, 20 min) will be delivered by a constant direct current electrical stimulator connected to a pair of electrodes
Placebo Comparator: Placebo treatment
For sham sDCS (placebo), electrodes will be placed as for active stimulation, but the stimulator will automatically turn off after 10 s.
Other: Placebo treatment
Electrodes will be placed as for active stimulation, but the stimulator will automatically turn off after 10 s

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
sDCS efficacy in pain as determined by NPSI and NRS scale
Time Frame: 30 days
Spinal DCS (sDCS) has been proven to modulate Nociceptive Withdrawal Reflex (NWR), an objective and sensitive tool to explore pain processing at the Spinal Level and recommended by European Federation of Neurological Society (EFNS) to evaluate the analgesic effect of treatments.
30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Central endocannabinoid level as determined by Activity of Fatty Acid Amide Hydrolase (FAAH) in platelets
Time Frame: 30 days
The endocannabinoid system is involved in descending central pain control and can be modulated by other neurostimulation techniques as transcutaneous electrical nerve stimulation. The investigators suppose that one of the major effect of sDCS is to modulate supraspinal central pain control through activation of endocannabinoid system inducing the analgesic effect. Alteration of endocannabinoid system activity is also involved in other pathological aspects of Multiple Sclerosis as spasms, spasticity and incontinence and to acute and chronic neurodegeneration (anti-oxidant activity and inhibition of glutamate release and signalling). Activity of Fatty Acid Amide Hydrolase (FAAH) in platelets will be quantify.
30 days
Spasticity as determined by Ashworth Scale
Time Frame: 30 days
As sDCS reduces NWR area and as it may modulate endocannabinoid system, the investigators could suppose other positive effects of this treatment in Multiple Sclerosis patients as reduction of painful spasms and spasticity. The investigators will evaluate the effect of sDCS on spasticity, if present, investigating its effect on validate ad hoc scales (Ashworth scale) and on neurophysiological acquisitions (H reflex).
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS National Neurological Institute "C. Mondino" Foundation

Investigators

  • Principal Investigator: Giorgio Sandrini, MD, IRCCS Fondazione Istituto Neurologico Nazionale C. Mondino

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2013

Primary Completion (Anticipated)

June 1, 2015

Study Completion (Anticipated)

February 1, 2016

Study Registration Dates

First Submitted

December 16, 2014

First Submitted That Met QC Criteria

January 5, 2015

First Posted (Estimate)

January 6, 2015

Study Record Updates

Last Update Posted (Estimate)

January 6, 2015

Last Update Submitted That Met QC Criteria

January 5, 2015

Last Verified

January 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2786/13

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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