Long-term Effects of Transcranial Direct Current Stimulation (tDCS) on Patients With Phantom Limb Pain (PLP)

Phantom Limb Pain Clinical Trial

Official title:

Long-Term Treatment of Patients Experiencing Phantom Limb Pain With Transcranial Direct Current Stimulation (tDCS)

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT02051959
• Other study ID #: SHEBA-13-0733-IS-CTIL
• Status: Suspended
• Phase: N/A
• First received: January 28, 2014
• Last updated: January 26, 2016
• Start date: May 2015
• Est. completion date: December 2017

Study information

• Verified date: January 2016
• Source: Sheba Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

• Phantom limb pain (PLP) refers to pain in a limb that has been amputated or deafferented. Phantom limb pain might be related to brain cortical plastic changes.

• The purpose of this study is to determine the efficacy of a series of transcranial direct current stimulation (tDCS) sessions, a non-invasive and focal brain stimulation method, in producing long-term reduction of phantom limb pain among amputees who experience such pain.

This is a Crossover sham control.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 24
• Est. completion date: December 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Age 18 to 80

• Limb amputation from at least 6 months before study enrollment

• Presence of PLP at least 2 times a week and present 4 weeks prior to onset of study

• Written informed consent

Exclusion Criteria:

• Coexistence of major neurological or psychiatric diseases

• Being actively enrolled in a separate study targeting pain relief

• Post traumatic stress disorder (PTSD) diagnosed patients

• Any contraindication to noninvasive brain stimulation such as past brain surgery, brain implants, cochlear implant, epilepsy or any past seizure

• Pregnant women

• Within the traumatic amputees group - subjects diagnosed with diabetes

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Phantom Limb
• Phantom Limb Pain

Intervention

Device:
• Anodal stimulation of M1 + sham
8 active treatmments: 2mA anodal stimulation of M1 for 20 minutes (over the relevant cortex area) followed by 8 sham treatments.
• Sham + Anodal stimulation of M1
8 sham treatments followed by 8 active treatmments: 2mA anodal stimulation of M1 for 20 minutes (over the relevant cortex area).
• Cathodal stimulation of M1 + sham
8 active treatmments: 2mA cathodal stimulation of M1 for 20 minutes (over the relevant cortex area) , followed by 8 sham treatments.
• Sham + Cathodal stimulation of M1
8 sham treatments followed by 8 active treatmments: 2mA cathodal stimulation of M1 for 20 minutes (over the relevant cortex area).

Locations

Country	Name	City	State
Israel	Department of Orthopedic Rehabilitation, Sheba Medical Center	Ramat Gan

Sponsors (1)

Lead Sponsor	Collaborator
Sheba Medical Center

Country where clinical trial is conducted

Israel, 

References & Publications (28)

Birbaumer N, Lutzenberger W, Montoya P, Larbig W, Unertl K, Töpfner S, Grodd W, Taub E, Flor H. Effects of regional anesthesia on phantom limb pain are mirrored in changes in cortical reorganization. J Neurosci. 1997 Jul 15;17(14):5503-8. — View Citation

Bolognini N, Olgiati E, Maravita A, Ferraro F, Fregni F. Motor and parietal cortex stimulation for phantom limb pain and sensations. Pain. 2013 Aug;154(8):1274-80. doi: 10.1016/j.pain.2013.03.040. Epub 2013 Apr 19. — View Citation

Brown JA, Barbaro NM. Motor cortex stimulation for central and neuropathic pain: current status. Pain. 2003 Aug;104(3):431-5. Review. — View Citation

Chen R, Corwell B, Yaseen Z, Hallett M, Cohen LG. Mechanisms of cortical reorganization in lower-limb amputees. J Neurosci. 1998 May 1;18(9):3443-50. — View Citation

Cohen LG, Bandinelli S, Findley TW, Hallett M. Motor reorganization after upper limb amputation in man. A study with focal magnetic stimulation. Brain. 1991 Feb;114 ( Pt 1B):615-27. — View Citation

Elbert T, Sterr A, Flor H, Rockstroh B, Knecht S, Pantev C, Wienbruch C, Taub E. Input-increase and input-decrease types of cortical reorganization after upper extremity amputation in humans. Exp Brain Res. 1997 Oct;117(1):161-4. — View Citation

Flor H, Elbert T, Knecht S, Wienbruch C, Pantev C, Birbaumer N, Larbig W, Taub E. Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation. Nature. 1995 Jun 8;375(6531):482-4. — View Citation

Flor H. Phantom-limb pain: characteristics, causes, and treatment. Lancet Neurol. 2002 Jul;1(3):182-9. Review. — View Citation

Fuhr P, Cohen LG, Dang N, Findley TW, Haghighi S, Oro J, Hallett M. Physiological analysis of motor reorganization following lower limb amputation. Electroencephalogr Clin Neurophysiol. 1992 Feb;85(1):53-60. — View Citation

Gandiga PC, Hummel FC, Cohen LG. Transcranial DC stimulation (tDCS): a tool for double-blind sham-controlled clinical studies in brain stimulation. Clin Neurophysiol. 2006 Apr;117(4):845-50. Epub 2006 Jan 19. — View Citation

Grüsser SM, Winter C, Mühlnickel W, Denke C, Karl A, Villringer K, Flor H. The relationship of perceptual phenomena and cortical reorganization in upper extremity amputees. Neuroscience. 2001;102(2):263-72. — View Citation

Hall EJ, Flament D, Fraser C, Lemon RN. Non-invasive brain stimulation reveals reorganized cortical outputs in amputees. Neurosci Lett. 1990 Aug 24;116(3):379-86. — View Citation

Karl A, Birbaumer N, Lutzenberger W, Cohen LG, Flor H. Reorganization of motor and somatosensory cortex in upper extremity amputees with phantom limb pain. J Neurosci. 2001 May 15;21(10):3609-18. — View Citation

Kew JJ, Ridding MC, Rothwell JC, Passingham RE, Leigh PN, Sooriakumaran S, Frackowiak RS, Brooks DJ. Reorganization of cortical blood flow and transcranial magnetic stimulation maps in human subjects after upper limb amputation. J Neurophysiol. 1994 Nov;72(5):2517-24. — View Citation

Khedr EM, Ahmed MA, Fathy N, Rothwell JC. Therapeutic trial of repetitive transcranial magnetic stimulation after acute ischemic stroke. Neurology. 2005 Aug 9;65(3):466-8. — View Citation

Khedr EM, Kotb H, Kamel NF, Ahmed MA, Sadek R, Rothwell JC. Longlasting antalgic effects of daily sessions of repetitive transcranial magnetic stimulation in central and peripheral neuropathic pain. J Neurol Neurosurg Psychiatry. 2005 Jun;76(6):833-8. — View Citation

Lefaucheur JP, Drouot X, Menard-Lefaucheur I, Zerah F, Bendib B, Cesaro P, Keravel Y, Nguyen JP. Neurogenic pain relief by repetitive transcranial magnetic cortical stimulation depends on the origin and the site of pain. J Neurol Neurosurg Psychiatry. 2004 Apr;75(4):612-6. — View Citation

Lotze M, Flor H, Grodd W, Larbig W, Birbaumer N. Phantom movements and pain. An fMRI study in upper limb amputees. Brain. 2001 Nov;124(Pt 11):2268-77. — View Citation

Nitsche MA, Liebetanz D, Antal A, Lang N, Tergau F, Paulus W. Modulation of cortical excitability by weak direct current stimulation--technical, safety and functional aspects. Suppl Clin Neurophysiol. 2003;56:255-76. Review. — View Citation

Nitsche MA, Liebetanz D, Lang N, Antal A, Tergau F, Paulus W. Safety criteria for transcranial direct current stimulation (tDCS) in humans. Clin Neurophysiol. 2003 Nov;114(11):2220-2; author reply 2222-3. — View Citation

Nitsche MA, Paulus W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol. 2000 Sep 15;527 Pt 3:633-9. — View Citation

Nuti C, Peyron R, Garcia-Larrea L, Brunon J, Laurent B, Sindou M, Mertens P. Motor cortex stimulation for refractory neuropathic pain: four year outcome and predictors of efficacy. Pain. 2005 Nov;118(1-2):43-52. Epub 2005 Oct 7. — View Citation

O'Connell NE, Cossar J, Marston L, Wand BM, Bunce D, Moseley GL, De Souza LH. Rethinking clinical trials of transcranial direct current stimulation: participant and assessor blinding is inadequate at intensities of 2mA. PLoS One. 2012;7(10):e47514. doi: 10.1371/journal.pone.0047514. Epub 2012 Oct 17. — View Citation

Poreisz C, Boros K, Antal A, Paulus W. Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients. Brain Res Bull. 2007 May 30;72(4-6):208-14. Epub 2007 Jan 24. — View Citation

Röricht S, Meyer BU, Niehaus L, Brandt SA. Long-term reorganization of motor cortex outputs after arm amputation. Neurology. 1999 Jul 13;53(1):106-11. — View Citation

Töpper R, Foltys H, Meister IG, Sparing R, Boroojerdi B. Repetitive transcranial magnetic stimulation of the parietal cortex transiently ameliorates phantom limb pain-like syndrome. Clin Neurophysiol. 2003 Aug;114(8):1521-30. — View Citation

Tsubokawa T, Katayama Y, Yamamoto T, Hirayama T, Koyama S. Chronic motor cortex stimulation for the treatment of central pain. Acta Neurochir Suppl (Wien). 1991;52:137-9. — View Citation

Yang TT, Gallen CC, Ramachandran VS, Cobb S, Schwartz BJ, Bloom FE. Noninvasive detection of cerebral plasticity in adult human somatosensory cortex. Neuroreport. 1994 Feb 24;5(6):701-4. — View Citation

* Note: There are 28 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduced phantom limb pain	Reduction of phantom limb pain compared to phantom limb pain before treatment, according to Visual Analog Scales (VAS) evaluation	5 months after last stimulation session	No
Secondary	Adverse effects of treatment	Severity of any adverse effects related to the transcranial direct current stimulation treatment will be checked after each stimulation session	Up to 5 weeks	Yes
Secondary	Effects of treatment on the electrical activity of the brain	Measurement of the electrical activity of the brain before, during and after each stimulation using an electroencephalography (EEG) device.	Up to 5 weeks	No