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Optimizing Rehabilitation for Phantom Limb Pain Using Mirror Therapy and Transcranial Direct Current Stimulation (tDCS)

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ClinicalTrials.gov Identifier: NCT02487966
Recruitment Status : Recruiting
First Posted : July 2, 2015
Last Update Posted : March 8, 2018
Sponsor:
Collaborator:
Massachusetts Eye and Ear Infirmary
Information provided by (Responsible Party):
Felipe Fregni, Spaulding Rehabilitation Hospital

Brief Summary:
This is a two-site study that explores the effects of mirror therapy and transcranial Direct Current Stimulation (tDCS, Soterix ©) in a randomized factorial controlled trial in which patients will be assigned to one of four groups: active tDCS and active MT; sham tDCS and active MT; active tDCS and sham MT (which consists of using a covered mirror for the therapy); and both sham tDCS and sham MT (covered mirror).

Condition or disease Intervention/treatment Phase
Phantom Limb Pain Amputation, Traumatic Device: transcranial Direct Current Stimulation (tDCS): active (Soterix ©) Behavioral: Mirror Therapy: active Device: transcranial Direct Current Stimulation (tDCS): sham (Soterix ©) Behavioral: Mirror Therapy: Sham Not Applicable

Detailed Description:

Phantom limb pain (PLP) belongs to a group of neuropathic pain syndromes that is characterized by pain in the amputated limb. Rehabilitation for chronic pain involves a structured treatment plan targeting all dimensions of the pain experience, and should include a comprehensive interdisciplinary approach that allows patients to receive the most benefit according to their needs. As in other chronic pain syndromes, chronic Phantom limb pain (PLP) is often difficult to treat; showing to be resistant to classical pharmacological and surgical treatment approaches.

In this context, we hypothesize that novel treatments of PLP need to target specific neural networks associated with this maladaptive plasticity. Transcranial direct current stimulation (tDCS,Soterix ©) is a powerful and non-invasive technique of brain stimulation that is known to significantly modulate plasticity and alleviate chronic pain in various syndromes. device for this trial. This study usiGiven tDCS underlying neural mechanisms, it is critical to use a multimodal approach to treatment - using both tDCS and behavioral therapy simultaneously. In this case, an ideal therapy is mirror therapy (MT).

Recently, we showed that anodal tDCS can induce a selective short-lasting relief from PLP, and repeated applications of anodal tDCS induces long-lasting analgesic effects. These preliminary results show that tDCS may be a promising rehabilitative tool for the management of chronic PLP. This neurorehabilitation technique is commonly used in PLP, and is designed to modulate cortical mechanisms of pain by performing movements using the unaffected limb in front of a mirror. We propose to carry out a mechanistic, factorial, randomized controlled trial to evaluate a novel rehabilitation approach combining tDCS and MT in PLP patients. We aim to compare the brain changes before and after treatment in order to study the mechanisms underlying PLP.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 132 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Optimizing Rehabilitation for Phantom Limb Pain Using Mirror Therapy and Transcranial Direct Current Stimulation (tDCS)
Study Start Date : July 2015
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Rehabilitation

Arm Intervention/treatment
Experimental: Active tDCS and Active Mirror Therapy
Subjects will receive 20 minutes of active tDCS, while receiving 15 minutes of active Mirror Therapy.
Device: transcranial Direct Current Stimulation (tDCS): active (Soterix ©)
Subjects will undergo tDCS stimulation. For both active and sham stimulation, we will use electrodes of 35cm^2, at an intensity of 2mA on the primary motor cortex contralateral to the amputated leg. For active tDCS, the subject will undergo stimulation for 20 minutes.

Behavioral: Mirror Therapy: active
Subjects will be asked to perform movements (15 minutes daily) using the unaffected limb while watching its mirrored reflection superimposed over the affected limb. During Mirror Therapy, subjects will be asked to consciously relate the movement observed in the mirror to their phantom limb and to keep their attention focused on the task. Instructions will be explained verbally, demonstrated by a therapist, and performed by the subject in front of the therapist.

Experimental: Active tDCS and sham Mirror Therapy
Subjects will receive 20 minutes of active tDCS, while receiving 15 minutes of sham Mirror Therapy.
Device: transcranial Direct Current Stimulation (tDCS): active (Soterix ©)
Subjects will undergo tDCS stimulation. For both active and sham stimulation, we will use electrodes of 35cm^2, at an intensity of 2mA on the primary motor cortex contralateral to the amputated leg. For active tDCS, the subject will undergo stimulation for 20 minutes.

Behavioral: Mirror Therapy: Sham
Subjects will be asked to perform movements (15 minutes daily) using the unaffected limb while watching its mirrored reflection superimposed over the affected limb, only the mirror will be covered. During Mirror Therapy, subjects will be asked to consciously relate the movement observed in the mirror to their phantom limb and to keep their attention focused on the task. Instructions will be explained verbally, demonstrated by a therapist, and performed by the subject in front of the therapist. We will use the same all of these techniques as active Mirror Therapy only the mirror will be covered during all activities.

Experimental: Sham tDCS and active Mirror Therapy
Subjects will receive 20 minutes of sham tDCS, while receiving 15 minutes of active Mirror Therapy.
Behavioral: Mirror Therapy: active
Subjects will be asked to perform movements (15 minutes daily) using the unaffected limb while watching its mirrored reflection superimposed over the affected limb. During Mirror Therapy, subjects will be asked to consciously relate the movement observed in the mirror to their phantom limb and to keep their attention focused on the task. Instructions will be explained verbally, demonstrated by a therapist, and performed by the subject in front of the therapist.

Device: transcranial Direct Current Stimulation (tDCS): sham (Soterix ©)
Subjects will undergo tDCS stimulation. For both active and sham stimulation, we will use electrodes of 35cm^2, at an intensity of 2mA on the primary motor cortex contralateral to the amputated leg. The subject will undergo stimulation for 20 minutes. This is the same parameters as the active one, except the current will be ramped up and then down again (for 30 seconds total) to simulate the feeling of active stimulation.

Sham Comparator: Sham tDCS and sham Mirrory Therapy
Subjects will receive 20 minutes of sham tDCS, while receiving 15 minutes of sham Mirror Therapy.
Device: transcranial Direct Current Stimulation (tDCS): sham (Soterix ©)
Subjects will undergo tDCS stimulation. For both active and sham stimulation, we will use electrodes of 35cm^2, at an intensity of 2mA on the primary motor cortex contralateral to the amputated leg. The subject will undergo stimulation for 20 minutes. This is the same parameters as the active one, except the current will be ramped up and then down again (for 30 seconds total) to simulate the feeling of active stimulation.

Behavioral: Mirror Therapy: Sham
Subjects will be asked to perform movements (15 minutes daily) using the unaffected limb while watching its mirrored reflection superimposed over the affected limb, only the mirror will be covered. During Mirror Therapy, subjects will be asked to consciously relate the movement observed in the mirror to their phantom limb and to keep their attention focused on the task. Instructions will be explained verbally, demonstrated by a therapist, and performed by the subject in front of the therapist. We will use the same all of these techniques as active Mirror Therapy only the mirror will be covered during all activities.




Primary Outcome Measures :
  1. Changes in the Visual Analog Scale for Phantom Limb Pain [ Time Frame: Measured for approximately 13-14 weeks ]
    The primary end point will be severity of pain measured by changes in PLP as indexed by a Visual Analog Scale (VAS).


Secondary Outcome Measures :
  1. Changes in the Visual Analog Scale for Phantom Limb Stump Pain [ Time Frame: Measured for approximately 13-14 weeks ]
    The end point will be severity of pain measured by changes in PLP as indexed by a Visual Analog Scale (VAS).

  2. Changes in the Visual Analog Scale for Phantom Limb Sensation [ Time Frame: Measured for approximately 13-14 weeks ]
    The end point will be severity of pain measured by changes in PLP as indexed by a Visual Analog Scale (VAS).

  3. Changes in the Visual Analog Scale for Phantom Limb telescoping [ Time Frame: Measured for approximately 13-14 weeks ]
    The end point will be severity of pain measured by changes in PLP as indexed by a Visual Analog Scale (VAS).

  4. Adapted Groningen Questionnaire after Arm Amputation [ Time Frame: Baseline (first visit after screening; usually will occur approximately within 1 week from enrollment) ]
    This questionnaire is originally meant to obtain information's concerning complaints that may be developed after arm amputation. We adapted the current arm version for lower limb amputation. This questionnaire has been used in several clinical trials assessing PLP.

  5. Pain and medication diary [ Time Frame: Measured for approximately 13-14 weeks ]
    To help monitor pain levels and medication use information, as well as safety. Subjects will be asked to record the number of phantom limb episodes on a daily basis, using a pain diary. They will record the intensity of the strongest episode as well as phantom limb sensation and stump pain on a colored visual analog scale included in the diary, where 0 represents no pain at all and 10 represents the highest pain the patient has ever felt. Moreover subjects will record their current medications and dosages daily in a pain medication diary, until completion of the study.

  6. Beck depression Inventory [ Time Frame: Screening (first study visit; usually done same day as enrollment) and follow-ups (~3-4, ~5-6, ~ 9-10, and ~13-15 weeks after enrollment) ]
    This self-report inventory consists of 21 multiple-choice questions and is widely used method to classify depression severity. It assesses for the presence of several symptoms related to depression, such as irritability, hopelessness and decreased cognitive performance. Physical symptoms such as weight loss and fatigue are also included. This instrument has been used previously to evaluate depression severity in patients with phantom limb pain, as well as in other chronic pain conditions.

  7. Beck anxiety Inventory [ Time Frame: Baseline (approximately within 1 week from enrollment) and follow-ups (~3-4, ~5-6, ~ 9-10, and ~13-15 weeks after enrollment) ]
    This self-report inventory consists of 21 multiple-choice questions about how the subject has been feeling in the last week, expressed as common symptoms of anxiety (such as numbness and tingling, sweating not due to heat, and fear of the worst happening). It is designed for an age range of 17-80 years old. Each question has the same set of four possible answer choices, which are arranged in columns and are answered by marking the appropriate one with a cross.

  8. Mini Mental State examination (MMSE) [ Time Frame: Baseline (approximately within 1 week from enrollment) ]
    This is a sensitive, valid and reliable 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. This instrument will be used as a brief screening of cognitive abilities. It will be used as a baseline evaluation

  9. Quality of Life Assessment (Short version of SF-36) [ Time Frame: Baseline (approximately within 1 week from enrollment) and some follow-ups (~5-6 weeks and ~13-14 weeks after enrollment) ]
    The short version of the SF-36 health survey is used as a measurement of quality of life. It provides a profile of functional health and well-being scores. It is also used as a psychometrical index of physical and mental health. This instrument is widely used as a quality of life assessment in patients after an amputation and those suffering from phantom limb pain.

  10. Stroop test [ Time Frame: Baseline (approximately within 1 week from enrollment) and some follow-ups (~3-4, ~5-6, and ~13-14 weeks after enrollment) ]
    In this task the subject is presented with names of colors written in the same color or in a different color, thus on the one hand the word names a color (red) and is written in another color (blue). In this task, the automatized behavior (reading) is in conflict with the desired response (naming the color). The Subject has to inhibit/suppress the automatic response of reading and naming the color the word is written in. The Stroop is one of the most commonly used tools for determining attentional problems, also used to assess executive function and working memory. Stroop test will be applied as a preliminary safety assessment of cognitive changes from baseline to post and follow-up visits.

  11. Side Effects Questionnaire for tDCS [ Time Frame: During the intervention sessions of tDCS (at least one 1 week after screening for 2 consecutive weeks) ]
    At each stimulation session, subjects will complete a questionnaire to evaluate potential adverse effects of tDCS (tingling, burning sensation, headache, neck pain, mood alterations) and mirror therapy (anxiety, grief, dizziness) on a 4-point scale (None, mild, moderate and severe). The subjects will be asked whether they have experienced any side effects in an open-ended manner and they will then be specifically asked about headache, neck pain, scalp pain, scalp burns, tingling, skin redness, sleepiness, trouble concentrating, and acute mood change. If any side effects are reported, the degree of relatedness to the intervention will be assessed on a 5-point scale. This type of adverse events questionnaire has been used frequently in our previous tDCS studies , including in patients with phantom limb pain .

  12. Side Effects Questionnaire for TMS [ Time Frame: During TMS evaluations: Baseline (approximately within 1 week from enrollment); last day of tDCS stimulation (~3-4 weeks from enrollment); last day mirror therapy (~5-6 weeks from enrollment); last follow-up (~13-14 weeks from enrollment) ]
    At each TMS assessment session, subjects will complete a questionnaire to evaluate potential adverse effects of rTMS (headache, neck pain, itching and redness at the site of stimulation) on a 5-point scale.

  13. tDCS blinding questionnaire [ Time Frame: Last day of tDCS sessions (~3-4 weeks from enrollment) ]
    After the stimulation session, subjects will complete a questionnaire to determine if our blinding methods were effective. We are using a 30s sham montage, just as we use in our other trials, keeping the device on the subject for the duration of the session

  14. Patient's Global Impression of Change scale [ Time Frame: Last day of Mirror Therapy (~5-6 weeks from enrollment) ]
    Subjects will complete a questionnaire to assess their perception of change (if any) in the activity limitations, symptoms, emotions and overall quality of life after their participation in intervention's visits of the trial

  15. Single and Paired Pulse TMS [ Time Frame: During TMS evaluations: Baseline (~within 1 week from enrollment); last day of t); last day of tDCS stimulation (~3-4 weeks from enrollment); last day mirror therapy (~5-6 weeks from enrollment); last follow-up (~13-14 weeks from enrollment) ]
    Subjects will undergo several sessions of TMS to assess cortical excitability and cortical reorganization.

  16. Functional magnetic resonance imaging (fMRI) [ Time Frame: Baseline (approximately within 1 week from enrollment) and last day of Mirror Therapy (~5-6 weeks from enrollment) ]
    This is to quantify maladaptive cortical reorganization before and after treatment.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Able to provide informed consent to participate in the study.
  2. Subject is older than 18 years.
  3. Unilateral lower limb amputation.
  4. Traumatic amputation greater than 1 year ago.
  5. Chronic PLP for at least 3 months previous to enrollment in the study, experienced regularly for at least once a week.
  6. Average pain of at least 4 on a numeric rating scale in the previous week (NRS; ranging from 0 to 10).
  7. If the subject is taking any medications, dosages must be stable for at least 2 weeks prior to the enrollment of the study.

Exclusion Criteria:

  1. Pregnancy or trying to become pregnant in the next 2 months.
  2. History of alcohol or drug abuse within the past 6 months as self-reported.
  3. Presence of the following contraindication to transcranial direct current stimulation and transcranial magnetic stimulation

    • Ferromagnetic metal in the head (e.g., plates or pins, bullets, shrapnel)
    • Implanted neck or head electronic medical devices (e.g., cochlear implants, vagus nerve stimulator)
  4. History of chronic pain previous to the amputation.
  5. Head injury resulting in loss of consciousness for at least 30 min or pos-traumatic amnesia for greater than 24 hours, as self-reported
  6. Unstable medical conditions (e.g. uncontrolled diabetes, uncompensated cardiac issues, heart failure or chronic obstructive pulmonary disease).
  7. Uncontrolled Epilepsy or prior seizures within the last 1 year.
  8. Suffering from severe depression (as defined by a score of >30 in the Beck Depression Inventory).*
  9. History of unexplained fainting spells or loss of consciousness as self-reported during the last 2 years.
  10. History of neurosurgery, as self-reported.
  11. Mirror Therapy in the previous 3 months

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02487966


Contacts
Contact: Felipe Fregni, MD, PhD, MPH 617-573-2326 ffregni@partners.org
Contact: Camilla Pinto, M.Sc. 617-952-6160 cbpinto@partners.org

Locations
United States, Massachusetts
Spaulding Rehabilitation Network Research Institute Recruiting
Charlestown, Massachusetts, United States, 02129
Contact: Felipe Fregni, MD PhD MPH    617-952-6156    ffregni@partners.org   
Contact: Camilla Pinto, M.Sc.    617-952-6160    cbpinto@partners.org   
Principal Investigator: Felipe Fregni, MD PhD MPH         
Brazil
IMREA HCFMUSP - Rede Lucy Montoro Recruiting
São Paulo, Brazil, 04116-030
Contact: Dra. Linamara Rizzo Battistella, MD PhD    55 (11) 5180-7800    linamara@usp.br   
Contact: Elice Carneiro, BS    55 (11) 5180-7897    elice.carneiro@hc.fm.usp.br   
Principal Investigator: Dra. Linamara Rizzo Battistella, MD PhD         
Sponsors and Collaborators
Spaulding Rehabilitation Hospital
Massachusetts Eye and Ear Infirmary
Investigators
Principal Investigator: Felipe Fregni, MD, PhD, MPH Spaulding Rehabilitation Hospital

Publications of Results:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Felipe Fregni, Principal Investigator, Spaulding Rehabilitation Hospital
ClinicalTrials.gov Identifier: NCT02487966     History of Changes
Other Study ID Numbers: 2015P001065
First Posted: July 2, 2015    Key Record Dates
Last Update Posted: March 8, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Felipe Fregni, Spaulding Rehabilitation Hospital:
tDCS
Mirror Therapy
Phantom Limb Pain
Traumatic amputation

Additional relevant MeSH terms:
Phantom Limb
Amputation, Traumatic
Perceptual Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Pain, Postoperative
Pain
Postoperative Complications
Pathologic Processes
Signs and Symptoms
Wounds and Injuries