Mechanisms and Treatment of Post-amputation Neuropathic Pain

NCT ID: NCT04819503

Last Updated: 2023-11-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-01
• Study Completion Date: 2021-12-03

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.

Conditions

Neuropathic Pain; Phantom Limb Pain; Amputation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: OTHER

Spinal anaesthesia (sub-study 1)

Intervention Type: DRUG

We will conduct two sub-studies on the same patient group. Sub-study 1 is an observational study where patients with phantom and/or residual limb pain after lower limb amputation will be given spinal anaesthesia with 1% Chloroprocaine in an open label manner to investigate whether the peripheral nervous system is a necessary driver of their pain.

Repetitive transcranial magnetic stimulation (sub-study 2)

Intervention Type: DEVICE

After sub-study 1, the same patients will enter sub-study 2 where they are randomly assigned to receive either first active rTMS (10 days over 2 weeks), and then after a 9 week washout period, sham rTMS (10 days over 2 weeks), or they first receive sham rTMS, and then after 9 weeks of washout, active rTMS. Thus, patients undergo stimulation with deep rTMS in a double blinded randomised controlled trial with a 2 x 2 cross-over design, receiving both active and placebo stimulation

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.

Group Type: OTHER

Spinal anaesthesia (sub-study 1)

Intervention Type: DRUG

We will conduct two sub-studies on the same patient group. Sub-study 1 is an observational study where patients with phantom and/or residual limb pain after lower limb amputation will be given spinal anaesthesia with 1% Chloroprocaine in an open label manner to investigate whether the peripheral nervous system is a necessary driver of their pain.

Repetitive transcranial magnetic stimulation (sub-study 2)

Intervention Type: DEVICE

After sub-study 1, the same patients will enter sub-study 2 where they are randomly assigned to receive either first active rTMS (10 days over 2 weeks), and then after a 9 week washout period, sham rTMS (10 days over 2 weeks), or they first receive sham rTMS, and then after 9 weeks of washout, active rTMS. Thus, patients undergo stimulation with deep rTMS in a double blinded randomised controlled trial with a 2 x 2 cross-over design, receiving both active and placebo stimulation

Interventions

Spinal anaesthesia (sub-study 1)

We will conduct two sub-studies on the same patient group. Sub-study 1 is an observational study where patients with phantom and/or residual limb pain after lower limb amputation will be given spinal anaesthesia with 1% Chloroprocaine in an open label manner to investigate whether the peripheral nervous system is a necessary driver of their pain.

Intervention Type: DRUG

Repetitive transcranial magnetic stimulation (sub-study 2)

After sub-study 1, the same patients will enter sub-study 2 where they are randomly assigned to receive either first active rTMS (10 days over 2 weeks), and then after a 9 week washout period, sham rTMS (10 days over 2 weeks), or they first receive sham rTMS, and then after 9 weeks of washout, active rTMS. Thus, patients undergo stimulation with deep rTMS in a double blinded randomised controlled trial with a 2 x 2 cross-over design, receiving both active and placebo stimulation

Intervention Type: DEVICE

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oslo University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Nadine Farnes

PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Audun Stubhaug, DMedSci

Role: STUDY_DIRECTOR

Oslo University Hospital

Locations

Department of Pain Management and Research, Oslo University Hospital and Faculty of Medicine, University of Oslo,

Oslo, , Norway

Countries

Norway

Other Identifiers

77110

Identifier Type: -

Identifier Source: org_study_id