Amputation, Traumatic, Phantom Limb Pain
Conditions
Keywords
tDCS, Mirror Therapy, Phantom Limb Pain, Traumatic amputation
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).
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.
Interventions
DEVICEtranscranial 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.
BEHAVIORALMirror 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.
DEVICEtranscranial 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.
BEHAVIORALMirror 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.
Sponsors
Massachusetts Eye and Ear Infirmary
Spaulding Rehabilitation Hospital
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in the Visual Analog Scale for Phantom Limb Pain | 4 weeks | The primary endpoint will be the severity of pain measured by changes in PLP from baseline to 4 weeks (value at 4 weeks minus value at baseline), as indexed by a Visual Analog Scale (VAS). The VAS pain scale is a simple 10- point scale (0 = ''no pain'', 10 = ''pain as bad as you can imagine''). Since we are using a difference, smaller values (negative) represent a better outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in the Visual Analog Scale for Stump Pain | 4 weeks | The endpoint will be the severity of pain measured by changes in Stump Pain from baseline to 4 weeks (value at 4 weeks minus value at baseline), as indexed by a Visual Analog Scale (VAS). The VAS Phantom Limb Stump Pain scale is a simple 10- point scale (0 = ''no Phantom Limb Stump Pain'', 10 = ''Phantom Limb Stump Pain as bad as you can imagine''). Since we are using a difference, smaller values (negative) represent a better outcome. |
| Changes in the Visual Analog Scale for Phantom Limb Sensation | 4 weeks | The endpoint will be the severity of pain measured by changes in Phantom Limb Sensation from baseline to 4 weeks (value at 4 weeks minus value at baseline), as indexed by a Visual Analog Scale (VAS). The VAS Phantom Limb Sensation scale is a simple 10- point scale (0 = ''no Phantom Limb Sensation'', 10 = ''Phantom Limb Sensation as much as you can imagine''). Since we are using a difference, smaller values (negative) represent a better outcome. |
Countries
Brazil, United States
Participant flow
Pre-assignment details
Please note that from 132 subjects enrolled, 112 started (were randomized) as 20 subjects screened out after signing the consent form (time commitment=8; loss of interest=5; no more phantom limb pain=3; personal reasons=4).
Participants by arm
| Arm | Count |
|---|---|
| Active tDCS and Active Mirror Therapy Subjects will receive 20 minutes of active tDCS, while receiving 15 minutes of active Mirror Therapy.
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.
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. | 29 |
| Active tDCS and Sham Mirror Therapy Subjects will receive 20 minutes of active tDCS, while receiving 15 minutes of sham Mirror Therapy.
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.
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. | 28 |
| Sham tDCS and Active Mirror Therapy Subjects will receive 20 minutes of sham tDCS, while receiving 15 minutes of active Mirror Therapy.
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.
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. | 28 |
| Sham tDCS and Sham Mirrory Therapy Subjects will receive 20 minutes of sham tDCS, while receiving 15 minutes of sham Mirror Therapy.
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.
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. | 27 |
| Total | 112 |
Baseline characteristics
| Characteristic | Active tDCS and Active Mirror Therapy | Active tDCS and Sham Mirror Therapy | Sham tDCS and Active Mirror Therapy | Sham tDCS and Sham Mirrory Therapy | Total |
|---|---|---|---|---|---|
| Age, Continuous | 48.24 years STANDARD_DEVIATION 16.28 | 39.96 years STANDARD_DEVIATION 15.96 | 46 years STANDARD_DEVIATION 12.73 | 42.96 years STANDARD_DEVIATION 12.28 | 44.34 years STANDARD_DEVIATION 14.82 |
| Phantom Limb Pain | 6.12 units on a scale STANDARD_DEVIATION 1.88 | 6.29 units on a scale STANDARD_DEVIATION 1.67 | 6.09 units on a scale STANDARD_DEVIATION 1.75 | 5.90 units on a scale STANDARD_DEVIATION 1.57 | 6.08 units on a scale STANDARD_DEVIATION 1.71 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 6 Participants | 6 Participants | 6 Participants | 25 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 5 Participants | 5 Participants | 5 Participants | 19 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) White | 14 Participants | 15 Participants | 15 Participants | 15 Participants | 59 Participants |
| Region of Enrollment Brazil | 19 Participants | 19 Participants | 18 Participants | 17 Participants | 73 Participants |
| Region of Enrollment United States | 10 Participants | 9 Participants | 10 Participants | 10 Participants | 39 Participants |
| Sex: Female, Male Female | 7 Participants | 10 Participants | 11 Participants | 10 Participants | 38 Participants |
| Sex: Female, Male Male | 22 Participants | 18 Participants | 17 Participants | 17 Participants | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 28 | 0 / 28 | 0 / 27 |
| other Total, other adverse events | 7 / 29 | 6 / 28 | 6 / 28 | 6 / 27 |
| serious Total, serious adverse events | 0 / 29 | 0 / 28 | 0 / 28 | 0 / 27 |
Outcome results
Primary
Changes in the Visual Analog Scale for Phantom Limb Pain
The primary endpoint will be the severity of pain measured by changes in PLP from baseline to 4 weeks (value at 4 weeks minus value at baseline), as indexed by a Visual Analog Scale (VAS). The VAS pain scale is a simple 10- point scale (0 = ''no pain'', 10 = ''pain as bad as you can imagine''). Since we are using a difference, smaller values (negative) represent a better outcome.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active tDCS and Active Mirror Therapy | Changes in the Visual Analog Scale for Phantom Limb Pain | -2.84 units on a scale | Standard Deviation 2.95 |
| Active tDCS and Sham Mirror Therapy | Changes in the Visual Analog Scale for Phantom Limb Pain | -3.35 units on a scale | Standard Deviation 3.24 |
| Sham tDCS and Active Mirror Therapy | Changes in the Visual Analog Scale for Phantom Limb Pain | -1.78 units on a scale | Standard Deviation 2.96 |
| Sham tDCS and Sham Mirrory Therapy | Changes in the Visual Analog Scale for Phantom Limb Pain | -2.58 units on a scale | Standard Deviation 2.78 |
Secondary
Changes in the Visual Analog Scale for Phantom Limb Sensation
The endpoint will be the severity of pain measured by changes in Phantom Limb Sensation from baseline to 4 weeks (value at 4 weeks minus value at baseline), as indexed by a Visual Analog Scale (VAS). The VAS Phantom Limb Sensation scale is a simple 10- point scale (0 = ''no Phantom Limb Sensation'', 10 = ''Phantom Limb Sensation as much as you can imagine''). Since we are using a difference, smaller values (negative) represent a better outcome.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active tDCS and Active Mirror Therapy | Changes in the Visual Analog Scale for Phantom Limb Sensation | -1.86 units on a scale | Standard Deviation 2.55 |
| Active tDCS and Sham Mirror Therapy | Changes in the Visual Analog Scale for Phantom Limb Sensation | -2.55 units on a scale | Standard Deviation 2.64 |
| Sham tDCS and Active Mirror Therapy | Changes in the Visual Analog Scale for Phantom Limb Sensation | -1.35 units on a scale | Standard Deviation 2.64 |
| Sham tDCS and Sham Mirrory Therapy | Changes in the Visual Analog Scale for Phantom Limb Sensation | -2.83 units on a scale | Standard Deviation 3.87 |
Secondary
Changes in the Visual Analog Scale for Stump Pain
The endpoint will be the severity of pain measured by changes in Stump Pain from baseline to 4 weeks (value at 4 weeks minus value at baseline), as indexed by a Visual Analog Scale (VAS). The VAS Phantom Limb Stump Pain scale is a simple 10- point scale (0 = ''no Phantom Limb Stump Pain'', 10 = ''Phantom Limb Stump Pain as bad as you can imagine''). Since we are using a difference, smaller values (negative) represent a better outcome.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active tDCS and Active Mirror Therapy | Changes in the Visual Analog Scale for Stump Pain | -1.31 units on a scale | Standard Deviation 2.99 |
| Active tDCS and Sham Mirror Therapy | Changes in the Visual Analog Scale for Stump Pain | -1.9 units on a scale | Standard Deviation 3.99 |
| Sham tDCS and Active Mirror Therapy | Changes in the Visual Analog Scale for Stump Pain | -0.91 units on a scale | Standard Deviation 2.94 |
| Sham tDCS and Sham Mirrory Therapy | Changes in the Visual Analog Scale for Stump Pain | -0.96 units on a scale | Standard Deviation 2.84 |