Clinical trial NCT06483035: Treatment of Phantom Limb Pain by Intensive Visual Simulation Therapy
Official title: Intensive Visual Simulation as Treatment for Chronic Phantom Limb Pain in Persons With Upper or Lower Limb Amputation - A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Phantom Limb Pain
Keywords: Amputation
Chronic pain
Intensive Visual Stimulation
RCT
Lead sponsor: Oslo Metropolitan University
Sponsor class: OTHER
First posted: 2024-07-01
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is a 2-arm randomized controlled trial with a parallel group design. If persons first allocated to Waiting list/Usual Care and then secondly to IVS treatment, are similar to those persons receiveing IVS treatment as the first treatment, a semi-crossover study design will be considered
Primary purpose: TREATMENT

Brief summary: Phantom limb pain (PLP) is reported by as much as 80 % of patients following an amputation. There is increasing knowledge of the relation between PLP and maladaptive changes in brain cortical regions. Research has shown that the sight of an "intact arm" moving in a mirror may reverse maladaptions (Mirror-therapy, MT) and reduce PLP.

The current project will implement a digital and modernized version of MT, i.e. Intensive Visual Simulation Therapy (IVS-T). Pilot studies have shown promising results on pain reduction in people with phantom limb pain when using IVS-T. However, there is a lack of RCT studies on this patient population.

This study is a 2-arm randomized controlled trial (RCT) investigating the effectiveness of IVS-T compared with usual care in person with unilateral upper- or lower limb amputation with chronic phantom limb pain.

The primary aim of the study is to investigate if IVS treatment is superior to usual care in reducing phantom limb pain intensity after 2 months of treatment in unilateral amputees with moderate to severe PLP.

The study will furthermore explore quality of life, analgesic consumption, phantom pain characteristics, mobility, and disability. In addition, the study utilizes brain imagery during treatments to investigate neural plasticity and the association between PLP and maladaptive cortical changes.

Detailed description: Phantom limb pain is pain experienced to arise from and reside in the amputated limb, hence the name, phantom limb pain. PLP is experienced by about 50-80 % after acquired limb loss. The pain can be excruciating, and chronic phantom limb pain (PLP) can have a truly devastating effect on a persons' life, affecting both physical function and quality of life. Unfortunately, phantom limb pain has proven difficult to treat both by pharmacological and non-pharmacological methods. Several treatment options have been suggested, but without showing strong research evidence for effect on PLP.

Over time, several mechanisms have been proposed to explain the occurrence of PLP, but the most cited reasons for the existence or development of phantom limb pain are theories connected to neuroplasticity, cortical reorganization and maladaptive changes due to loss of sensory input and motor control (e. g. Pons. Science, 1991). Several studies have observed that phantom limb pain is closely associated with neuroplastic changes in the somatosensory and motor cortex of the brain. Although these are maladaptive changes, the fact that the adult brain retains a neuroplastic capacity also opens a therapeutic widow of opportunity, i. e. it makes it possible to envision non-invasive therapies that exploits the principles of brain plasticity in the treatment of phantom limb pain by designing treatments that conceivably may reverse maladaptive changes and possibly reduce PLP.

Relating to this, functional activity of the affected limb, including the use of a prosthesis, has been seen to have a positive effect on PLP, and this effect is believed to be partly explained by an effect of motor activity of the remaining stump on brain cortical activity and possibly cortical reorganization (Mosely and Floor Neurorehabilitation and Neural Repair, 2012). This is also the rationale behind classical interventions such as "mirror therapy", first proposed by Ramachandran (Nature, 1995).

The present study will investigate the effect of a novel method for treatment of phantom limb pain that extends the concept of mirror therapy. This new method entails viewing a virtual limb (phantom limb) on a large screen, that "substitute" the missing limb. In short, the treatment starts with making a videorecording of the intact limb of the patient performing different predetermined movements. This recording is then digitally "flipped" and two "intact" limbs are then displayed on a large screen in front of the patient. The amputated limb is hidden below the screen. The patient is then asked to execute a set of movements with the (hidden) amputated limb, and at the same time the person will observe the phantom limb on the screen perform the exact same (prerecorded) movements. This treatment protocol is called Intensive Visual Simulation Therapy (IVS) and extends the concept of mirror therapy, where only the intact and healthy limb is performing movements and there is no motor planning or motor execution of the amputated limb.

In this project, the effect of the IVS method on reduction of phantom limb pain will be compared to "Usual Care" (UC), which will be considered the standard treatment. Persons with either unilateral upper or lower limb amputation will be included in this study. In conjunction with use of these two therapeutic approaches, advanced, neuroimaging tools (functional near-infrared spectroscopy; fNIRS) will be implemented with the purpose of investigating the neurological responses to IVS treatment. As opposed to functional magnetic resonance imaging (fMRI), the fNIRS system allows the measurement of brain activity in a more "naturalistic" setting, like when the participants "execute" movements with the phantom limb in the IVS system.

Participants in this study will be randomized to either IVS or UC treatment. Measurement of PLP and other outcome measures will be performed at baseline, after eight weeks of IVS or UC and at 2 months follow-up. Persons in the UC group shall continue with their standard treatment for this entire period (8+8 weeks). Persons in the IVS group will receive two treatment sessions per week for eight weeks and then no treatment in the follow-up period (8 weeks). The UC group will have the opportunity to receive IVS treatment after terminating their follow-up period.

Eligibility criteria: Inclusion Criteria:

* Unilateral or bilateral lower limb/upper limb amputees
* Adults \&gt; 18 years of age, no age limit
* A minimum of 12 months since amputation
* Chronic PLP: \&gt; 6 months
* PLP intensity: \&gt; 3 on the 0-10 VAS scale
* Analgesic treatments must have been stable for the previous month
* Stable prosthetic situation (ie, satisfaction with the fitting of the prosthesis) or being a non-user.
* Adequate Norwegian language skills

Exclusion Criteria:

* Significant visual impairment / blind
* Unable to follow instructions, i.e significant cognitive impairment.

Primary outcomes:
measure: Phantom limb pain intensity- 14 day pain dairy
timeFrame: Measured at Baseline (0 months), at the end of Intervention (2 months after Baseline) and at the end of Follow-up (4 months after Baseline)
Secondary outcomes:
measure: Health related quality of life
timeFrame: Assessed at 0 months (Baseline), immediately at the end of intervention (2 months) and immediately at the end of follow-up (4 months)
measure: Pain characteristics
timeFrame: Assessed at 0 months (Baseline), immediately at the end of intervention (2 months) and immediately at the end of follow-up (4 months)
measure: Upper Extremity Function
timeFrame: Assessed at 0 months (Baseline), immediately at the end of intervention (2 months) and immediately at the end of follow-up (4 months)
measure: Lower Extremity Function
timeFrame: Assessed at 0 months (Baseline), immediately at the end of intervention (2 months) and immediately at the end of follow-up (4 months)
measure: Concentration (micromolar levels) of oxygenated (oxyHb) and deoxygenated (deoxyHb) hemoglobin in specific brain cortical regions of interest (ROIs)
timeFrame: During 2nd week and 8th week of IVS treatment
measure: Phantom pain intensity before and after treatment sessions
timeFrame: At each session immediately before and after treatment. Each participant will receive a maximum of 16 treatment sessions over a period of eight weeks
Other outcomes:
measure: Quality of Life (QoL)
timeFrame: Assessed at 0 months (Baseline), immediately at the end of intervention (2 months) and immediately at the end of follow-up (4 months)
measure: Health Status Score on a VAS scale
timeFrame: Assessed at 0 months (Baseline), immediately at the end of intervention (2 months) and immediately at the end of follow-up (4 months)
measure: Use of analgesics
timeFrame: The participants use of analgesics is assessed during the last week prior to start of IVS or UC treatment and immediately after eight weeks of IVS or UC treatment
measure: Adverse events
timeFrame: Assessed immediately at the end of intervention (2 months after baseline) and at end of follow-up (4 months after baseline)
measure: Sociodemographic variables
timeFrame: Assessed at baseline (0 months)
measure: Cause of amputation
timeFrame: Assessed at baseline (0 months)
measure: Level of amputation
timeFrame: Assessed at baseline (0 months)
measure: Hours of daily prosthetic use
timeFrame: Assessed at 0 months (Baseline), immediately at the end of intervention (2 months) and immediately at the end of follow-up (4 months)
measure: Experience of phantom limb sensations
timeFrame: Assessed at 0 months (Baseline), immediately at the end of intervention (2 months) and immediately at the end of follow-up (4 months)
measure: Presence of comorbidities
timeFrame: Assessed at baseline (0 months)
Locations:
city: Oslo
country: Norway
facility: Oslo Metropolitan University
Study officials:
affiliation: Oslo Metropolitan University
name: Terje Gjøvaag, PhD
role: PRINCIPAL_INVESTIGATOR
References: