Examining Brain Changes Using Functional Magnetic Resonance Imaging (fMRI) in Amputees With Phantom Limb Pain Following Mirror Therapy - Full Text View

Sponsors and Collaborators:	Department of Defense National Institute of Mental Health (NIMH)
Information provided by:	Walter Reed Army Medical Center
ClinicalTrials.gov Identifier:	NCT00662415

Purpose

Almost everyone who has a traumatic limb amputated will experience a phantom limb - the vivid impression that the limb not only still is present, but also in many cases, painful. Preliminary data from study WRAMC WU# 05-71034, "Pilot study to assess the efficacy of mirror-box and mental visualization treatments on phantom limb pain" demonstrates that 4 weeks of mirror therapy is effective for treating phantom limb pain (PLP) and suggests that vision is a key component modulating PLP and may be the explanation for the efficacy of mirror therapy, as subjects view the reflected image of their intact limb while attempting to move the amputated, or phantom, limb. We propose conducting a study using functional magnetic resonance imaging (fMRI) to identify brain regions critical for the mirror effect and to study the relationship of visual activation to the sensation of phantom pain. Subjects will have an fMRI scan prior to starting therapy, 2 weeks after starting mirror therapy and again after 4 weeks of mirror therapy. Data will be gathered daily on the number of episodes of phantom limb pain, the average length of episodes, and the average intensity of pain.

Condition	Intervention
Phantom Limb Pain	Device: mirror-box treatment Behavioral: observation

Study Type:	Interventional
Study Design:	Basic Science, Non-Randomized, Open Label, Parallel Assignment
Official Title:	Study Using Functional MRI to Examine Changes in the Brain in Unilateral Lower Limb Amputees Treated With Mirror Therapy for Phantom Limb Pain.

Resource links provided by NLM:

MedlinePlus related topics: Amputees MRI Scans

U.S. FDA Resources

Further study details as provided by Walter Reed Army Medical Center:

Primary Outcome Measures:

The identification of brain regions activated before and after treatment with mirror therapy. [ Time Frame: 0, 2, and 4 weeks ] [ Designated as safety issue: No ]
phantom limb pain as measured using the VAS and McGill [ Time Frame: daily for 4 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	42
Study Start Date:	February 2008
Estimated Study Completion Date:	February 2010
Estimated Primary Completion Date:	February 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1 12 non-amputee control subjects will be scanned at 0, 2 and 4 weeks but will not recieve mirror therapy.	Behavioral: observation observation
2: Experimental 24 unilateral lower extremity amputee subjects will recieve daily mirror therapy for phantom limb pain and will be scanned at 0, 2, and 4 weeks.	Device: mirror-box treatment 15 minutes daily for 4 weeks

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

For Amputee Subjects:

Male or female subjects
18 to 75 years of age
Active duty military
Military healthcare beneficiary
Military retiree
Written informed consent and written authorization for use or release of health and research study information
Unilateral lower limb amputation
Right-handed
Any level of prosthetic experience
No prior history of vertebral disk disease/condition
Sciatica
Radiculopathy
Neurological examination that will not interfere with participation in the study
Minimum of 3 phantom limb pain episodes each week
Degree of pain evaluated by VAS scoring a minimum of 3 cm at time of screening for entry into study.
Ability to follow study instructions and likely to complete all required visits

For Control Subjects:

Male or female subjects
18 to 75 years of age
Written informed consent and written authorization for use or release of health and research study information
Right-handed.
No prior history of vertebral disk disease/condition
Sciatica
Radiculopathy
Normal neurological examination
Ability to follow study instructions and likely to complete all required visits

Exclusion Criteria:

For Amputee Subjects:

Age less than 18 or greater than 75 years
Unilateral upper limb or multiple limb amputation.
Amputation due to diabetes or vascular claudication
No known pending revision surgeries
Presence of embedded metallic shrapnel or other metal not compatible with MRI scanning
Presence of traumatic brain injury - permanent or temporary impairments of cognitive, physical, and psychosocial functions with an associated diminished or altered state of consciousness - as indicated by neuropsychological screening, including DVBIC testing, which is currently performed routinely on patients by the TBI program at WRAMC and noted in the patient's medical record
Known uncontrolled systemic disease- known cancer not in remission
Known on-going infection
Lupus
Kidney disease requiring dialysis, any other systemic disease which might affect ability to participate in this study to its conclusion
Concurrent participation in another investigational drug or device study for phantom limb pain or participation in the 30 days immediately prior to study enrollment
Any condition or situation that, in the investigator's opinion, may put the subject at significant risk, confound the study results, or interfere significantly with the subject's participation in the study
Significant Axis I or II diagnosis determined by a neurologist or psychiatrist in the 6 months prior to entry into the study
Subjects with lack of effort as determined by the neurologist or physiatrist
Subjects will be screened for effort using the Test of Memory Malingering (TOMM) first in order to exclude those with blatant exaggeration or malingering

For Control Subjects:

Age less than 18 or greater than 75 years
Presence of an amputation
Presence of embedded metallic shrapnel or other metal not compatible with MRI scanning
Presence of traumatic brain injury - permanent or temporary impairments of cognitive, physical, and psychosocial functions with an associated diminished or altered state of consciousness - as indicated by neuropsychological screening which is currently performed routinely on patients by the TBI program at WRAMC and noted in the patient's medical record
Known uncontrolled systemic disease- known cancer not in remission
Known on-going infection
Lupus
Kidney disease requiring dialysis
Any other systemic disease which might affect ability to participate in this study to its conclusion
Any condition or situation that, in the investigator's opinion, may put the subject at significant risk, confound the study results, or interfere significantly with the subject's participation in the study
Significant Axis I or II diagnosis determined by a neurologist or psychiatrist in the 6 months prior to entry into the study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00662415

Contacts

Contact: Jack W Tsao, MD	(301) 295-9684	tsaoj@grc.nia.nih.gov
Contact: Christopher Baker, PhD	(301) 435-6058

Locations

United States, District of Columbia
Walter Reed Army Medical Center	Recruiting
Washington, District of Columbia, United States, 20307
Contact: Jack W Tsao, MD 301-295-9684 tsaoj@grc.nia.nih.gov
United States, Maryland
National Institutes of Health	Recruiting
Bethesda, Maryland, United States, 20892
Contact: Christopher Baker, PhD 301-435-6058

Sponsors and Collaborators

Department of Defense

National Institute of Mental Health (NIMH)

More Information

Publications:

Ramachandran VS, Hirstein W. The perception of phantom limbs. The D. O. Hebb lecture. Brain. 1998 Sep;121 ( Pt 9):1603-30. Review.

Sherman RA, Sherman CJ, Parker L. Chronic phantom and stump pain among American veterans: results of a survey. Pain. 1984 Jan;18(1):83-95.

Jensen TS, Krebs B, Nielsen J, Rasmussen P. Phantom limb, phantom pain and stump pain in amputees during the first 6 months following limb amputation. Pain. 1983 Nov;17(3):243-56.

Browder J, Gallagher JP. Dorsal Cordotomy for Painful Phantom Limb. Ann Surg. 1948 Sep;128(3):456-69. No abstract available.

Schug SA, Burrell R, Payne J, Tester P. Pre-emptive epidural analgesia may prevent phantom limb pain. Reg Anesth. 1995 May-Jun;20(3):256. No abstract available.

Wall JT. Variable organization in cortical maps of the skin as an indication of the lifelong adaptive capacities of circuits in the mammalian brain. Trends Neurosci. 1988 Dec;11(12):549-57. Review. No abstract available.

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.

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.

Adrian ED, Zotterman Y. The impulses produced by sensory nerve-endings: Part II. The response of a Single End-Organ. J Physiol. 1926 Apr 23;61(2):151-71. No abstract available.

Garraghty PE, Kaas JH. Functional reorganization in adult monkey thalamus after peripheral nerve injury. Neuroreport. 1991 Dec;2(12):747-50.

WIESEL TN, HUBEL DH. SINGLE-CELL RESPONSES IN STRIATE CORTEX OF KITTENS DEPRIVED OF VISION IN ONE EYE. J Neurophysiol. 1963 Nov;26:1003-17. No abstract available.

Elbert T, Flor H, Birbaumer N, Knecht S, Hampson S, Larbig W, Taub E. Extensive reorganization of the somatosensory cortex in adult humans after nervous system injury. Neuroreport. 1994 Dec 20;5(18):2593-7.

Lotze M, Laubis-Herrmann U, Topka H, Erb M, Grodd W. Reorganization in the primary motor cortex after spinal cord injury - A functional Magnetic Resonance (fMRI) study. Restor Neurol Neurosci. 1999;14(2-3):183-187.

Merzenich MM, Nelson RJ, Stryker MP, Cynader MS, Schoppmann A, Zook JM. Somatosensory cortical map changes following digit amputation in adult monkeys. J Comp Neurol. 1984 Apr 20;224(4):591-605.

Pons TP, Garraghty PE, Ommaya AK, Kaas JH, Taub E, Mishkin M. Massive cortical reorganization after sensory deafferentation in adult macaques. Science. 1991 Jun 28;252(5014):1857-60.

Ramachandran VS. Blind spots. Sci Am. 1992 May;266(5):86-91. No abstract available.

Ramachandran VS, Rogers-Ramachandran D. Synaesthesia in phantom limbs induced with mirrors. Proc Biol Sci. 1996 Apr 22;263(1369):377-86.

Franz EA, Ramachandran VS. Bimanual coupling in amputees with phantom limbs. Nat Neurosci. 1998 Oct;1(6):443-4. No abstract available.

MacLachlan M, McDonald D, Waloch J. Mirror treatment of lower limb phantom pain: a case study. Disabil Rehabil. 2004 Jul 22-Aug 5;26(14-15):901-4.

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.

Lotze M, Grodd W, Birbaumer N, Erb M, Huse E, Flor H. Does use of a myoelectric prosthesis prevent cortical reorganization and phantom limb pain? Nat Neurosci. 1999 Jun;2(6):501-2. No abstract available.

Bauer L, O'Bryant SE, Lynch JK, McCaffrey RJ, Fisher JM. Examining the Test Of Memory Malingering Trial 1 and Word Memory Test Immediate Recognition as screening tools for insufficient effort. Assessment. 2007 Sep;14(3):215-22.

Price DD, Bush FM, Long S, Harkins SW. A comparison of pain measurement characteristics of mechanical visual analogue and simple numerical rating scales. Pain. 1994 Feb;56(2):217-26.

Melzack R. The short-form McGill Pain Questionnaire. Pain. 1987 Aug;30(2):191-7.

Buccino G, Binkofski F, Fink GR, Fadiga L, Fogassi L, Gallese V, Seitz RJ, Zilles K, Rizzolatti G, Freund HJ. Action observation activates premotor and parietal areas in a somatotopic manner: an fMRI study. Eur J Neurosci. 2001 Jan;13(2):400-4.

Desmond JE, Glover GH. Estimating sample size in functional MRI (fMRI) neuroimaging studies: statistical power analyses. J Neurosci Methods. 2002 Aug 30;118(2):115-28.

Lenth RV. Statistical power calculations. J Anim Sci. 2007 Mar;85(13 Suppl):E24-9. Epub 2006 Oct 23.

Study ID Numbers:	DCI-0771043
Study First Received:	March 14, 2008
Last Updated:	April 14, 2008
ClinicalTrials.gov Identifier:	NCT00662415 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by Walter Reed Army Medical Center:

phantom limb pain
fMRI
mirror therapy

Study placed in the following topic categories:

Signs and Symptoms
Neurologic Manifestations
Pain

Phantom Limb
Neurobehavioral Manifestations
Perceptual Disorders

Additional relevant MeSH terms:

Signs and Symptoms
Nervous System Diseases
Neurologic Manifestations

Phantom Limb
Neurobehavioral Manifestations
Perceptual Disorders

ClinicalTrials.gov processed this record on September 10, 2009