Spinal Direct Current Stimulation Effects on Pain in Multiple Sclerosis

NCT ID: NCT02331654

Last Updated: 2015-01-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-11-30

Study Completion Date

2016-02-29

Brief Summary

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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.

Detailed Description

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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

Conditions

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Multiple Sclerosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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.

Group Type EXPERIMENTAL

Experimental treatment

Intervention Type OTHER

Anodal DC stimulation (2 mA, 20 min) will be delivered by a constant direct current electrical stimulator connected to a pair of electrodes

Placebo treatment

For sham sDCS (placebo), electrodes will be placed as for active stimulation, but the stimulator will automatically turn off after 10 s.

Group Type PLACEBO_COMPARATOR

Placebo treatment

Intervention Type OTHER

Electrodes will be placed as for active stimulation, but the stimulator will automatically turn off after 10 s

Interventions

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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

Intervention Type OTHER

Placebo treatment

Electrodes will be placed as for active stimulation, but the stimulator will automatically turn off after 10 s

Intervention Type OTHER

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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IRCCS National Neurological Institute "C. Mondino" Foundation

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Giorgio Sandrini, MD

Role: PRINCIPAL_INVESTIGATOR

IRCCS Fondazione Istituto Neurologico Nazionale C. Mondino

Locations

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IRCCS Fondazione Istituto Neurologico Nazionale C. Mondino

Pavia, Pavia, Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Cinzia Fattore, MD

Role: CONTACT

+39 0382 380818

Facility Contacts

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Giorgio Sandrini, MD

Role: primary

+39 0382 380435

References

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Solaro C, Brichetto G, Amato MP, Cocco E, Colombo B, D'Aleo G, Gasperini C, Ghezzi A, Martinelli V, Milanese C, Patti F, Trojano M, Verdun E, Mancardi GL; PaIMS Study Group. The prevalence of pain in multiple sclerosis: a multicenter cross-sectional study. Neurology. 2004 Sep 14;63(5):919-21. doi: 10.1212/01.wnl.0000137047.85868.d6.

Reference Type BACKGROUND
PMID: 15365151 (View on PubMed)

O'Connor AB, Schwid SR, Herrmann DN, Markman JD, Dworkin RH. Pain associated with multiple sclerosis: systematic review and proposed classification. Pain. 2008 Jul;137(1):96-111. doi: 10.1016/j.pain.2007.08.024. Epub 2007 Oct 24.

Reference Type BACKGROUND
PMID: 17928147 (View on PubMed)

Nitsche MA, Seeber A, Frommann K, Klein CC, Rochford C, Nitsche MS, Fricke K, Liebetanz D, Lang N, Antal A, Paulus W, Tergau F. Modulating parameters of excitability during and after transcranial direct current stimulation of the human motor cortex. J Physiol. 2005 Oct 1;568(Pt 1):291-303. doi: 10.1113/jphysiol.2005.092429. Epub 2005 Jul 7.

Reference Type BACKGROUND
PMID: 16002441 (View on PubMed)

Ferrucci R, Mameli F, Guidi I, Mrakic-Sposta S, Vergari M, Marceglia S, Cogiamanian F, Barbieri S, Scarpini E, Priori A. Transcranial direct current stimulation improves recognition memory in Alzheimer disease. Neurology. 2008 Aug 12;71(7):493-8. doi: 10.1212/01.wnl.0000317060.43722.a3. Epub 2008 Jun 4.

Reference Type BACKGROUND
PMID: 18525028 (View on PubMed)

Fregni F, Thome-Souza S, Nitsche MA, Freedman SD, Valente KD, Pascual-Leone A. A controlled clinical trial of cathodal DC polarization in patients with refractory epilepsy. Epilepsia. 2006 Feb;47(2):335-42. doi: 10.1111/j.1528-1167.2006.00426.x.

Reference Type BACKGROUND
PMID: 16499758 (View on PubMed)

O'Connell NE, Wand BM, Marston L, Spencer S, Desouza LH. Non-invasive brain stimulation techniques for chronic pain. A report of a Cochrane systematic review and meta-analysis. Eur J Phys Rehabil Med. 2011 Jun;47(2):309-26. Epub 2011 Apr 14.

Reference Type BACKGROUND
PMID: 21494222 (View on PubMed)

Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O'Connor PW, Sandberg-Wollheim M, Thompson AJ, Weinshenker BG, Wolinsky JS. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol. 2005 Dec;58(6):840-6. doi: 10.1002/ana.20703.

Reference Type BACKGROUND
PMID: 16283615 (View on PubMed)

Cruccu G, Anand P, Attal N, Garcia-Larrea L, Haanpaa M, Jorum E, Serra J, Jensen TS. EFNS guidelines on neuropathic pain assessment. Eur J Neurol. 2004 Mar;11(3):153-62. doi: 10.1111/j.1468-1331.2004.00791.x.

Reference Type BACKGROUND
PMID: 15009162 (View on PubMed)

Sandrini G, Serrao M, Rossi P, Romaniello A, Cruccu G, Willer JC. The lower limb flexion reflex in humans. Prog Neurobiol. 2005 Dec;77(6):353-95. doi: 10.1016/j.pneurobio.2005.11.003. Epub 2005 Dec 28.

Reference Type BACKGROUND
PMID: 16386347 (View on PubMed)

Berra E, Bergamaschi R, De Icco R, Dagna C, Perrotta A, Rovaris M, Grasso MG, Anastasio MG, Pinardi G, Martello F, Tamburin S, Sandrini G, Tassorelli C. The Effects of Transcutaneous Spinal Direct Current Stimulation on Neuropathic Pain in Multiple Sclerosis: Clinical and Neurophysiological Assessment. Front Hum Neurosci. 2019 Feb 12;13:31. doi: 10.3389/fnhum.2019.00031. eCollection 2019.

Reference Type DERIVED
PMID: 30809137 (View on PubMed)

Other Identifiers

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2786/13

Identifier Type: -

Identifier Source: org_study_id

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