TITAN Trial: Reducing Phantom Limb Pain in People With Amputations

Study Overview
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Brief Summary
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The goal of this clinical trial is to investigate the effectiveness of two rehabilitation programs for individuals who have undergone amputations and are experiencing phantom limb pain. The main question it aims to answer is: - In individuals who have undergone amputations and are experiencing phantom limb pain, what is the effectiveness of a progressive rehabilitation program compared to a treatment program consisting of transcutaneous electrical nerve stimulation and cranial electrical stimulation on reducing pain intensity and pain interference? A total of 208 participants will be randomized into two groups: progressive rehabilitation program and stimulation devices. The progressive rehabilitation program includes pain science education, sensory training, and left/right judgements, imagined movements and mirror therapy. The treatment program for the group receiving the stimulation devices includes transcutaneous electrical nerve stimulation and cranial electrical stimulation. Both interventions will be delivered via eight, up to 1-hour telehealth sessions. Outcome measures will be assessed at baseline and weeks 12, 24 and 52.

Official Title
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TITAN: a Randomised Controlled Trial Investigating the Effectiveness of Two Treatment Programs for Reducing Phantom Limb Pain Intensity and Its Interference With Function

Conditions
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Phantom Limb Pain, Amputation

Intervention / Treatment
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* Other: Progressive rehabilitation program
* Other: Stimulation devices


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Experiencing phantom limb pain for at least three months. Report at least one episode of phantom limb pain in the previous week. Report at least 4 points in pain intensity over the previous 7 days, assessed using the 11-point Numerical Pain Rating Scale. Be a resident in Australia for the intervention and follow-up period. Have access to the internet and smart device (e.g., mobile phone). Be proficient in English. Exclusion Criteria: Bilateral amputation. Scheduled for major surgery during the study period. Pain in the intact limb. Vision impairment that would preclude successful participation. Auditory impairment that would preclude successful participation. Cognitive problems that would preclude effective participation in trial procedures (e.g., Alzheimer's, dementia). Previously diagnosed neurological disorders that affect the movement of the intact limb (e.g., stroke, Parkinson, Multiple Sclerosis). Completed Graded Motor Imagery in the order of left/right judgements, imagined movements, and mirror therapy.

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Progressive rehabilitation program<br>The progressive rehabilitation program is a multicomponent intervention, including pain science education, sensory training, implicit and explicit motor imagery, and mirror therapy. | Other: Progressive rehabilitation program<br>* Twelve-week treatment program delivered via eight, up to 1-hour telehealth sessions. The first five sessions will be scheduled every week, and the final three sessions will be scheduled fortnightly. Participants will also be prescribed approximately 15-30 minutes of home activities daily. The treatment program includes pain science education, sensory training, implicit and explicit motor imagery, and mirror therapy. Participants will complete activities at a self-directed pace following a standard progression protocol. Participant adherence will be measured via session attendance and self-report therapy diaries.<br>|
| Experimental: Stimulation devices<br>The treatment program includes Transcutaneous Electrical Nerve Stimulation and Cranial Electrical Stimulation. Participants will complete activities at a self-directed pace following a standard progression protocol. | Other: Stimulation devices<br>* Twelve-week treatment program delivered via eight, up to 1-hour telehealth sessions. The first five sessions will be scheduled every week, and the final three sessions will be scheduled fortnightly. Participants will also be prescribed approximately 15-30 minutes of home activities daily. The treatment program includes transcutaneous electrical nerve stimulation and cranial electrical stimulation. Participants will complete activities at a self-directed pace following a standard progression protocol. Participant adherence will be measured via session attendance and self-report therapy diaries.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity | Average pain intensity over the previous 7 days assessed using the 11-point Numerical Pain Rating Scale. | Week 12 post-randomisation | 
| Pain interference | Average pain interference with function over the previous 7 days assessed using the 0-10 Pain Interference Scale of the Brief Pain Inventory. | Week 12 post-randomisation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity | Average pain intensity over the previous 7 days assessed using the 11-point Numerical Pain Rating Scale. | Weeks 24 and 52 post-randomisation | 
| Pain interference | Average pain interference with function over the previous 7 days assessed using the 0-10 Pain Interference Scale of the Brief Pain Inventory. | Weeks 24 and 52 post-randomisation | 
| Pain severity | Average pain intensity over the previous 7 days assessed using the 0-10 Pain Severity Scale of the Brief Pain Inventory. | Weeks 12, 24 and 52 post-randomisation | 
| Sleep subscale of the Brief Pain Inventory's Pain Interference Scale | Sleep Quality assessed using the Sleep subscale of the Brief Pain Inventory's Pain Interference Scale. The participants will rate the interference of pain with sleep on a 0-10 scale where 0 represents does not interfere and 10 represents completely interferes. | Weeks 12, 24 and 52 post-randomisation | 
| PROMIS Self-Efficacy Manage Symptoms | Pain Self-efficacy assessed using PROMIS Self-Efficacy Manage Symptoms (Computer Adaptive Test) (28-item version; higher scores mean more self-efficacy). | Weeks 12, 24 and 52 post-randomisation | 
| PROMIS Depression | Emotional distress and depression assessed using PROMIS Depression (Computer Adaptive Test) (28-item version; higher scores mean more depression). | Weeks 12, 24 and 52 post-randomisation | 
| EuroQol 5-Dimension 5-Level (EQ-5D-5L) | Health-Related Quality of Life assessed using the EQ-5D-5L dimensions scale range, 1-5; higher scores indicate better quality of life) and health thermometer (range, 0-100; higher scores indicate better quality of life). | Weeks 12, 24 and 52 post-randomisation | 
| Global Perceived Effect Scale | Perception of recovery assessed using the Global Perceived Effect scale (range from -5 to +5; higher scores mean greater improvement). | Weeks 12, 24 and 52 post-randomisation | 
| Adverse events | Adverse events assessed via self-report. | From randomisation to week 12 post-randomisation | 
| Adherence to treatment | Adherence to treatment assessed via session attendance and self-report (diary), including frequency per week and duration per day. | From randomisation to week 12 post-randomisation | 
| Total health-care costs | Total health-care costs will be estimated as the trial intervention costs and outside trial health-care resource use attributable to phantom limb pain from the Medicare Benefits Scheme and Pharmaceutical Benefits Scheme. Quality-adjusted life-years (QALYs) from the EQ-5D-5L using the Australian utility weights will also be used in the trial-based cost-utility analysis. | Weeks 12, 24 and 52 post-randomisation |