Sensory Retraining for Phantom Limb Pain

Study Overview
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Brief Summary
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86-87% of people who have had an amputation still feel pain in the limb that has been amputated - Phantom limb pain (PLP). Sensory retraining is a form of treatment for PLP where a special form of electrical stimulation is delivered to the residual limb. The theory is that this stimulation changes activity in the brain that helps to reduce the person's pain. Two new types of sensory retraining device for the treatment of phantom limb pain have been developed. One type requires the user to interact with the device while the other is a non-interactive device. Both devices are new so it is unknown as to how well they may work, or which is best, therefore both will be tested in this study. This study will be undertaken remotely, using video call, telephone and email for communication. The study will compare the effect of both devices for efficacy. One hundred people with PLP will be recruited from the NHS and the general public and randomised to receive either the interactive or non-interactive device or their placebo equivalents. A health care professional will train the research participants how to use their device. Participants will then use their device at home for 3 weeks. To ensure that they are using their devices as required, the researchers will keep in contact throughout the three week treatment period, using a schedule of video calls, weekly phone calls and daily texts. Pain and function will be measured before treatment, after treatment and at a 3 month follow-up. Twelve participants will also be invited to a one-to-one interview to give their experience of the acceptability and usability of their device.

Official Title
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An Investigation of the Efficacy of a Novel Sensory Discrimination Training Device for the Management of Phantom Limb Pain: A Randomised, Single-blind, Placebo-controlled Trial. [PHANTOM RELIEF Trial]

Conditions
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Phantom Limb Pain

Intervention / Treatment
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* Device: Sensory retraining device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Living in the UK All Genders Aged ≥18 years of age People who self-declare at that they are not pregnant and could never become pregnant. Anyone who does not make both of those self-declarations: if it is at all possible (self-declaration at eligibility checking) they may be pregnant before the Trial but not know they are - will be required to undertake a highly sensitive urine pregnancy test (as close in time as possible to the first video call) and return (and share at the first videocall) a negative result and/or if it is at all possible (self-declaration at eligibility checking) that they may become pregnant, during the 21 days they will be using a device - will be required to use a form of contraception considered to be highly or acceptably effective by the Clinical Trials Facilitation and Coordination Group (CTFG, 2020) (listed below*) fully healed residual limb (or stump) ** single or multi limb amputation with the intervention applied to the participants limb of choice experienced PLP rated as ≥4 on a 0-10 scale on at least 2 days in the week prior to enrolment agree to inform us of the use of any new (to them) prescribed drug for their pain during the study any prescribed pharmacological treatment for the treatment of PLP stable for one month prior to commencing the study, and agree not to undertake any non-pharmacological treatments for their PLP during the study (e.g., mirror therapy) agree to inform us of any other health care received related to the amputated limb during the study (e.g., physiotherapy or occupational therapy) whether specific to PLP or not any previous non-pharmacological PLP treatment must have terminated at least 1 month prior to commencing the study Participants will need access to a mobile smart phone and a device (laptop, iPad etc.) at home to receive text messages and take part in secure video conference calls and completion of online forms. * Highly effective contraceptive methods being: Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation either oral, intravaginal, or transdermal Progestogen only hormonal contraception associated with inhibition of ovulation, either oral, injectable, or implantable Intrauterine device IUD Intrauterine hormone-releasing system IUS Sexual abstinence Acceptably effective contraceptive methods being: Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action Male or female condom with or without spermicide Cap, diaphragm or sponge with spermicide A combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods) (CTFG, 2020). Fully healed criteria: no bleeding, no oozing, no broken skin, no obvious sign of infection, such as swelling or redness, around the scar. Exclusion Criteria: lacking Mental Capacity to give Informed Consent people who self-declare that they are pregnant people who self-declare that they will be trying to become pregnant, during the 21 days they will be using a device impaired sensation as measured by hot/ cold test and sharp/ blunt test unable to read and speak English - the questionnaires being used have not been translated and validated in multiple languages and no facility is available to conduct nor translate/ back-translate semi-structured interview data epileptic active deep vein thrombosis, thrombophlebitis, or varicose veins fitted with a pacemaker has a metal implant in the area to be stimulated any residual limb complications such as cellulitis, wounds, infections etc. Active regions of known or suspected malignancy Any actively bleeding tissue or to persons with untreated haemorrhagic disorders Participating in any research trial of any intervention hypothesised to affect PLP Any current or recent history of substance misuse, alcohol, or drug dependency Any person, otherwise eligible, who commences any non-pharmacological treatment for PLP during the study period

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomised, single blind, controlled, mixed-methods study.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sensory Retraining Interactive Device<br>The interactive device is a sensory retraining device. A pad consisting of twelve equally spaced electrodes is placed over the residual limb. This pad is connected to a handheld device which delivers an electrical current to the electrodes. The type of electrical current is similar to a TENS device. The device stimulates the skin via one of the electrodes, with either a single, or a rapid burst of pulse(s). The device touch screen then presents the questions, Which electrode (location) was stimulated? Was a single continuous or a rapid burst of pulses given (stimulation type)? The user responds via the screen and is told if they are correct. If correct, a new stimulus is delivered (different location and type) and the process repeated. If incorrect, the user is informed of the correct response, the same stimulation (location and type) is repeated once before moving onto to a new stimulus. | Device: Sensory retraining device<br>* All participants will be given a device to keep at home and will be asked to use it for 60 minutes each day, as one block, or as multiple shorter sessions of 20 minutes minimum duration. Participants will be asked to use their device on 15 of the 21 days. They will be asked to spread out the use of the device over the 21 days. Participants are asked to record device use in a diary.<br>|
| Placebo Comparator: Placebo Sensory Retraining Interactive Device<br>The placebo device is visually identical to the active device | Device: Sensory retraining device<br>* All participants will be given a device to keep at home and will be asked to use it for 60 minutes each day, as one block, or as multiple shorter sessions of 20 minutes minimum duration. Participants will be asked to use their device on 15 of the 21 days. They will be asked to spread out the use of the device over the 21 days. Participants are asked to record device use in a diary.<br>|
| Active Comparator: Sensory Retraining Non-Interactive Device<br>The non-interactive device is physically visually identical to the interactive device. This device delivers the stimulation using microcurrents that the participants may or may not feel. There is no interaction required with this device i.e. there is no Q&A element, feedback nor response dependent progression. | Device: Sensory retraining device<br>* All participants will be given a device to keep at home and will be asked to use it for 60 minutes each day, as one block, or as multiple shorter sessions of 20 minutes minimum duration. Participants will be asked to use their device on 15 of the 21 days. They will be asked to spread out the use of the device over the 21 days. Participants are asked to record device use in a diary.<br>|
| Placebo Comparator: Placebo Sensory Retraining Non-Interactive Device<br>The placebo device is visually identical to the active device | Device: Sensory retraining device<br>* All participants will be given a device to keep at home and will be asked to use it for 60 minutes each day, as one block, or as multiple shorter sessions of 20 minutes minimum duration. Participants will be asked to use their device on 15 of the 21 days. They will be asked to spread out the use of the device over the 21 days. Participants are asked to record device use in a diary.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The short form McGill Pain Questionnaire (SF-MPQ-2) | The short form McGill Pain Questionnaire (SF-MPQ-2) (Dworkin et al, 2009): The short from McGill Pain Questionnaire (SF-MPQ-2) is a commonly used questionnaire to assess pain levels in a range of pain conditions. Twenty words which describe pain across the sensory, affective, evaluative and miscellaneous domains are presented to the participant who is asked to choose which word best describes their pain in the last week and to rate how intense that descriptor of pain was on a 0-10 scale. | Day 1 (baseline prior to start) and Day 21 (end) of treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The short form McGill Pain Questionnaire (SF-MPQ-2) | The short form McGill Pain Questionnaire (SF-MPQ-2) (Dworkin et al, 2009): The short from McGill Pain Questionnaire (SF-MPQ-2) is a commonly used questionnaire to assess pain levels in a range of pain conditions. Twenty words which describe pain across the sensory, affective, evaluative and miscellaneous domains are presented to the participant who is asked to choose which word best describes their pain in the last week and to rate how intense that descriptor of pain was on a 0-10 scale. | 3 month follow up point post end of treatment period | 
| Overall Pain: Visual Analogue Scale (100mm): | Participants will be asked to rate their phantom limb pain over the last week using a pain visual analogue scale consisting of a 100mm line with anchor statements of 0 representing no pain and 100 the worst pain imaginable. The participant will be asked to place a mark through the line to represent their pain. Participants will be asked to record the number of phantom limb pain episodes they have experienced over the past week. | Day 1 (baseline prior to start) and Day 21 (end) of treatment period and at 3 month follow up point post end of treatment | 
| Frequency adjusted pain score: (0-100) | Participants will be asked to record the frequency of PLP episodes they have experienced over the past week from 1 = all the time to 5 = Once a day or less per week. The overall pain score will be divided by the frequency value to create a composite frequency adjusted pain score ranging from 0-100. | Day 1 (baseline prior to start) and Day 21 (end) of treatment period and at 3 month follow up point post end of treatment | 
| Trinity Amputation and prosthetic evaluation scale (modified) (TAPES) | Participants will be asked to complete a modified version of the Trinity Amputation and prosthetics evaluation scale (TAPES scale).The TAPES has been modified in that it only asks about issues specific to PLP, residual limb (or stump) pain, and phantom sensations. | Day 1 (baseline prior to start) and Day 21 (end) of treatment period and at 3 month follow up point post end of treatment | 
| EQ5D5L | A brief easy to use validated measure of quality of life. The EQ5D contains five items related to mobility, self-care, usual activities, pain and anxiety/depression. It also contains a visual analogue scale for rating general health. | DDay 1 (baseline prior to start) and Day 21 (end) of treatment period and at 3 month follow up point post end of treatment | 
| Sleep Disturbance | Participants will be asked to complete the PROMIS Short Form v.1.0 - Sleep Disturbance 4a questionnaire. This is a self-reported questionnaire reporting perceptions of sleep quality, sleep depth, and restoration associated with sleep. It assesses sleep disturbance over the past seven days. There are four questions, each containing a 5-point Likert Scale, ranging from Very Poor to Very Good. The questions are then combined to create a score out of 100 (Gershan et al. 2010). | Day 1 (baseline prior to start) and Day 21 (end) of treatment period and at 3 month follow up point post end of treatment | 
| Study Diary (medication use/device use/pain levels) | Participants will be asked to report on their daily medication usage over the duration of the trial in a study diary. The participant will be sent a daily notification by the SMART-TRIAL platform to remind them to complete the study diary for the three week treatment period. The diary will ask for the frequency, dosage and class of medication taken each day. In addition, patients will be asked to rate their phantom limb pain on a scale from 0-10 each day, the frequency of those pain episodes, and to record how many minutes they used the device each day. | Each Day Days 1 (baseline prior to start) to Day 21 (end) of treatment period and at 3 month follow up point post end of treatment | 
| General Subjective Outcome Score (GSOS) | Participants will be asked to rate their level of improvement Choosing one of six options, ranging from a lot worse to completely better (Harland et al. 2015). | Day 21 (end) of treatment period and at 3 month follow up point post end of treatment | 
| Participant satisfaction | Six item rating scale. Participants will be asked to answer the question, How likely are you to recommend the device to other people who had phantom limb pain following an amputation? by choosing one of six options, ranging from extremely likely to extremely unlikely. | Day 21 (end) of treatment period and at 3 month follow up point post end of treatment | 
| Usability | After treatment, to investigate usability, all participants will be asked to rate how easy do you think the SensTrain was to use on a Visual Analogue Scale (VAS) (100mm) with 0 representing not at all easy to use and 100 representing extremely easy to use. | Day 21 (end) of treatment period | 
| Concordance with Protocol | The frequency and duration of use of the SP1X device will be documented in the daily study diary and compared against the protocol that participants were asked to adhere to. This data will also be automatically captured by the device. | Each Day Days 1 (baseline prior to start) to Day 21 (end) of treatment period | 
| Participant perceptions of usability and acceptability of the device they received | Semi-structured interview. | At 3 month follow up point post end of treatment | 
| Credibility of Devices | Participants will be asked Which of the following four devices do you think you received? 1. A real interactive device, 2. A sham/placebo interactive device, 3. A real non-interactive device or 4. A sham/placebo non-interactive device? And then How confident are you that your device was (form inserts answer 1,2,3 or 4) on a 0-100 scale with 0 being not at all confident and 100 being completely confident? | At 3 month follow up point post end of treatment | 
| Adverse Events & Reactions | All Adverse & Reactions will be recorded and reported as required | Throughout Data Collection Period |