Dependency of the Peripheral Nervous System as a Driver for Post-amputation Pain and Therapeutic Effects of Deep Repetitive Transcranial Magnetic Stimulation in a Randomized Double-blind Sham-controlled Study
Overview
- Phase
- Not Applicable
- Intervention
- Spinal anaesthesia (sub-study 1)
- Conditions
- Neuropathic Pain
- Sponsor
- Oslo University Hospital
- Enrollment
- 1
- Locations
- 1
- Primary Endpoint
- Percentage spontaneous pain intensity reduction (sub-study 1)
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief Summary
Phantom and residual limb pain are types of peripheral neuropathic pain that are difficult to treat and where the underlying mechanisms are still not fully understood. Repetitive transcranial magnetic stimulation (rTMS) of the motor cortex is an increasingly studied technique for the treatment of neuropathic pain and has shown modest effects in pain intensity reduction for the treatment of neuropathic pain. Newer rTMS coils provide the opportunity to stimulate larger brain areas, which could provide a better treatment option compared to conventional coils. The aims of this study are to investigate whether the peripheral nervous system is a necessary driver of phantom limb pain and/or residual limb pain in patients with lower limb amputation using spinal anaesthesia, and to assess the analgesic efficacy of deep H-coil rTMS compared to sham stimulation in the same patients.
Investigators
Nadine Farnes
PhD
Oslo University Hospital
Eligibility Criteria
Inclusion Criteria
- •18-80 years of age
- •Unilateral or bilateral lower limb amputation resulting in residual limb pain and/or phantom pain, fulfilling the criteria for definite neuropathic pain
- •Usual pain intensity at least 4/10 over the past 24 hrs using the numerical scale of the BPI at screening
- •Daily pain
- •Pain for at least 3 months
- •Stable pharmacological treatment for pain or no pharmaceutical treatment at least 1 month prior to the study
- •Patients who can be followed for the whole duration of the study
- •Minimum 4/10 pain intensity at the time of spinal anaesthesia for sub-study 1
Exclusion Criteria
- •Any clinically significant or unstable medical or psychiatric disorder
- •Subjects protected by law (guardianship or tutelage measure)
- •History of or current substance abuse (alcohol, drugs)
- •Pending litigation
- •Contraindications to spinal anaesthetic block (e.g. use of prescribed or non-prescribed medication that can increase risk of bleeding such as anticoagulants, non-steroidal anti-inflammatory drugs and acetylsalicylic acid)
- •Contraindication to rTMS (past severe head trauma, history of epilepsy or ongoing epilepsy, active cerebral tumour, past neurosurgical intervention, intracranial hypertension, implanted devices not compatible such as cardiac pacemaker and neurostimulator, cochlear implants, pregnancy or lactation. All women of childbearing age will be required to have negative pregnancy test at inclusion and to be using contraception)
- •Other pain conditions more severe than phantom and residual limb pain.
- •Inability to understand the protocol or to fill out the forms
- •Other ongoing research protocol or recent past protocol within one month before the inclusion
Arms & Interventions
Active and then sham repetitive transcranial magnetic stimulation
Deep rTMS is delivered with the Brainsway H7-coil (Brainsway, Jerusalem, Israel) applied via a helmet placed on the head targeting the primary motor cortex of the leg. Sham stimulation is delivered with a sham coil placed in the helmet encasing the active rTMS coil. Sham rTMS sessions will use exactly the same parameters of stimulation as active rTMS.
Intervention: Spinal anaesthesia (sub-study 1)
Active and then sham repetitive transcranial magnetic stimulation
Deep rTMS is delivered with the Brainsway H7-coil (Brainsway, Jerusalem, Israel) applied via a helmet placed on the head targeting the primary motor cortex of the leg. Sham stimulation is delivered with a sham coil placed in the helmet encasing the active rTMS coil. Sham rTMS sessions will use exactly the same parameters of stimulation as active rTMS.
Intervention: Repetitive transcranial magnetic stimulation (sub-study 2)
Sham and then active repetitive transcranial magnetic stimulation
Deep rTMS is delivered with the Brainsway H7-coil (Brainsway, Jerusalem, Israel) applied via a helmet placed on the head targeting the primary motor cortex of the leg.Sham stimulation is delivered with a sham coil placed in the helmet encasing the active rTMS coil. Sham rTMS sessions will use exactly the same parameters of stimulation as active rTMS.
Intervention: Spinal anaesthesia (sub-study 1)
Sham and then active repetitive transcranial magnetic stimulation
Deep rTMS is delivered with the Brainsway H7-coil (Brainsway, Jerusalem, Israel) applied via a helmet placed on the head targeting the primary motor cortex of the leg.Sham stimulation is delivered with a sham coil placed in the helmet encasing the active rTMS coil. Sham rTMS sessions will use exactly the same parameters of stimulation as active rTMS.
Intervention: Repetitive transcranial magnetic stimulation (sub-study 2)
Outcomes
Primary Outcomes
Percentage spontaneous pain intensity reduction (sub-study 1)
Time Frame: Maximum reduction during a time interval from 5-60 minutes after spinal anaesthesia
Measured on an 11-point numerical rating scale (0 %= no pain reduction; 100 % = complete pain reduction).
Change in usual pain intensity over the past 24 hours from baseline to 1 week after each treatment (sub-study 2
Time Frame: Average of usual pain scores one week before each treatment (baseline week) and 1 week after each treatment
Usual pain intensity over the past 24 hours is measured on a 11-point numerical rating scale (0 = no pain, 10 = worst pain intensity imaginable of the current pain condition) every day in a diary at the same hour (end of the day). Analgesic efficacy of active and sham treatment is considered the decrease in usual pain intensity scores between the average of each baseline week (one week before treatment) and average of 1 week after last stimulation of each treatment.
Secondary Outcomes
- Pin-prick sensitivity (sub-study 1)(Measured before, 5 minutes and 30 minutes after spinal anaesthesia)
- Pain intensity (sub-study 2)(Before, 1 week and 3 weeks after the end of each stimulation period)
- Intensity of pressure induced allodynia (sub-study 1)(Measured before, 5 minutes and 30 minutes after spinal anaesthesia)
- Spontaneous pain intensity right now (sub-study 1)(Measured before, and 5, 10, 15, 20, 25, 30, 60, 90 and 120 minutes after spinal anaesthesia)
- Insomnia Severity Index (sub-study 2)(Before,1 week and 3 weeks after the end of each stimulation period)
- Executive functioning using the CANTAB battery(Before,1 week and 3 weeks after the end of each stimulation period)
- Side-effects (sub-study 2)(Immediately after the first rTMS session for both stimulation periods, before and after all other rTMS sessions, and 1 week and 3 weeks after each stimulation period)
- Pain unpleasantness (sub-study 2)(Before, 1 week and 3 weeks after the end of each stimulation period)
- Pain diary of pain duration, paroxysms and pain interference on sleep (sub-study 2)(Every day 1 week before each stimulation period and up to three weeks after)
- Proportion of responders (sub-study 2)(Before,1 week and 3 weeks after the end of each stimulation period)
- Neuropathic Pain Symptom Inventory (sub-study 2)(Before,1 week and 3 weeks after the end of each stimulation period)
- Short form McGill Pain questionnaire (sub-study 2)(Before,1 week and 3 weeks after the end of each stimulation period)
- Hospital Anxiety and Depression Scale (sub-study 2)(Before,1 week and 3 weeks after the end of each stimulation period)
- Intensity of brush induced allodynia (sub-study 1)(Measured before, 5 minutes and 30 minutes after spinal anaesthesia)
- Pain interference (sub-study 2)(Before,1 week and 3 weeks after the end of each stimulation period)
- Usual pain intensity over the past 24 hours (sub-study 2)(Analgesic efficacy of active and sham treatment is measured as the decrease in pain intensity scores between baseline values (one week before treatment) and 3 weeks after the last stimulation.)
- Percentage pain intensity reduction (sub-study 2)(Before,1 week and 3 weeks after the end of each stimulation period)
- Pain Catastrophizing Scale (sub-study 2)(Before,1 week and 3 weeks after the end of each stimulation period)
- Patient Global Impression of Change (sub-study 2)(Before,1 week and 3 weeks after the end of each stimulation period)
- Patient-Specific Functional Scale (sub-study 2)(Before,1 week and 3 weeks after the end of each stimulation period)
- Blinding (sub-study 2)(3 weeks after the end of each stimulation period)