Operant Conditioning for Phantom Limb Pain

(OCS-PLP Trial)

Overseen By Disha Gupta, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Disqualifiers: Uncontrolled diabetes, Cardiac condition, Cognitive difficulties, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 26

Duration: 8-9 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to reduce phantom limb pain (PLP) through operant conditioning, which trains the brain to change its responses. PLP commonly affects individuals who have lost a limb, often causing long-lasting pain that complicates daily life. The trial tests whether feedback to adjust brain activity, known as Operant Conditioning with Peripheral Stimulation, can lessen this pain. Participants suitable for this study have moderate to severe phantom limb pain from an amputation that occurred over six months ago. As an unphased trial, this study offers participants the chance to contribute to innovative research that could lead to new treatments for PLP.

Will I have to stop taking my current medications?

The trial requires that you keep taking your current medications without any changes for at least 4 months from the start of the study.

What prior data suggests that this operant conditioning approach is safe for reducing phantom limb pain?

Research has shown that operant conditioning with peripheral stimulation can help alleviate phantom limb pain. In one study, 14 patients used neurofeedback training, which led to positive changes in brain activity and reduced their pain. Another study found that pain levels dropped by 32% just four days after starting the real training, with even more improvement by day eight.

These results suggest that the treatment is generally well-tolerated. No major side effects were reported in these studies, making it a safe option for many people with phantom limb pain. This treatment focuses on retraining the brain instead of using medication, which might appeal to those seeking non-drug options. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a novel approach to managing phantom limb pain through operant conditioning with peripheral stimulation. Unlike traditional treatments that typically involve medication or surgery, this method focuses on retraining the brain's response to phantom sensations using real-time feedback. The innovative technique combines peripheral stimulation with operant conditioning, potentially offering a non-invasive and drug-free alternative that could lead to more sustainable pain relief. By targeting the brain's adaptability, this approach could open new avenues for treating a condition that affects many amputees.

What evidence suggests that operant conditioning with peripheral stimulation could be effective for phantom limb pain?

Research shows that certain techniques can effectively reduce phantom limb pain. In this trial, participants in the intervention group will receive Operant Conditioning with Peripheral Stimulation, which includes brain-computer interface (BCI) training. Studies using BCI training, which involves technology to enhance brain communication, have shown promising results, with pain scores dropping by 32% within just a few days. Meanwhile, the control group will receive Peripheral Stimulation without operant conditioning feedback. These methods help the brain adjust after limb loss, which is linked to reducing pain. Overall, evidence suggests this approach could be a helpful non-drug option for managing phantom limb pain. ^{1 2 4 6 7}

Who Is on the Research Team?

Jodi A Brangaccio, PT

Principal Investigator

Albany VA Medical Center Samuel S. Stratton, Albany, NY

Are You a Good Fit for This Trial?

This trial is for adults over 18 who've had an arm or leg amputated more than 6 months ago and suffer from moderate to severe phantom limb pain. They should be stable on current medications, if any, able to follow study instructions, and have medical clearance. Those with heart conditions, unstable health issues like uncontrolled diabetes, cognitive difficulties, skin disorders at the EEG site, or metal implants above the chest cannot join.

Inclusion Criteria

Able to provide informed consent and to understand the study instructions

Medical clearance to participate

I can follow the study's required procedures.

Exclusion Criteria

I do not have any uncontrolled medical conditions like severe diabetes.

I have trouble focusing or remembering, which may affect my ability to follow study instructions.

I do not have any skin issues or wounds on my scalp where an EEG would be placed.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive peripheral stimulation with operant conditioning feedback training or without it, three 1-hour sessions per week

8-9 weeks

24-27 visits (in-person)

Follow-up

Participants are monitored for changes in somatosensory evoked potential and pain at 3 and 6 months after treatment

6 months

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Control Group with Peripheral Stimulation Only
• Operant Conditioning with Peripheral Stimulation

Trial Overview The study tests a non-drug technique called operant conditioning alongside peripheral stimulation to reduce phantom limb pain in amputees. Participants will receive real-time brain feedback aimed at normalizing sensorimotor responses. The control group receives only peripheral stimulation without this targeted brain training.

How Is the Trial Designed?

Group I: Intervention Group Experimental Treatment 1 Intervention

Intervention group receives peripheral stimulation with realtime operant conditioning feedback training.

Group II: Control Group Experimental Treatment 1 Intervention

Control group receives peripheral stimulation but without operant conditioning feedback.

Operant Conditioning with Peripheral Stimulation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Operant Conditioning Therapy for:

• Phantom Limb Pain Management
• Chronic Pain Relief

Approved in European Union as Neurofeedback Training for:

• Phantom Limb Pain Reduction
• Neuropathic Pain Management

Approved in Canada as Brain-Computer Interface Therapy for:

• Chronic Pain Management
• Rehabilitation After Amputation

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

A clinical trial involving 67 participants with phantom limb pain is investigating the effectiveness of phantom motor execution (PME) compared to phantom motor imagery (PMI) in relieving pain, with participants receiving 15 sessions of each treatment.

The study aims to determine if PME can provide greater relief from phantom limb pain and improve related symptoms, with follow-up assessments planned at 1, 3, and 6 months post-treatment to evaluate long-term benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statistical analysis plan for an international, double-blind, randomized controlled clinical trial on the use of phantom motor execution as a treatment for phantom limb pain. Lendaro, E., Earley, EJ., Ortiz-Catalan, M.[2022]

Neurofeedback training was successfully tested in 14 patients with phantom limb pain, showing that it can change sensorimotor cortical representations without requiring actual movements of the phantom limb.

The study found that contralateral neurofeedback training led to increased pain levels compared to ipsilateral training, suggesting a direct relationship between altered phantom hand representations and pain perception.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurofeedback Training without Explicit Phantom Hand Movements and Hand-Like Visual Feedback to Modulate Pain: A Randomized Crossover Feasibility Trial. Yanagisawa, T., Fukuma, R., Seymour, B., et al.[2023]

Operant and cognitive behavioral treatments have been found effective in managing chronic pain, highlighting the importance of learning procedures in pain development.

Future research should explore the potential benefits of combining these behavioral treatments with pharmacological agents to enhance pain management outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Operant and cognitive behavioural treatments in chronic pain]. Diers, M.[2018]

The operant learning theory, as applied to chronic pain management, emphasizes the importance of pain behaviors and their influence by environmental factors, which has been supported by various experimental studies.

Three key therapeutic techniques—graded activity, activity pacing, and time-contingent medication management—are highlighted for their effectiveness in treating chronic pain, with discussions on their mechanisms of action and suggestions for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Operant learning theory in pain and chronic pain rehabilitation. Gatzounis, R., Schrooten, MG., Crombez, G., et al.[2021]

In a pilot study involving nine individuals with phantom limb pain (PLP), biofeedback treatment showed promising results, with five patients experiencing a 20% reduction in pain after four sessions and six out of seven patients achieving at least a 30% reduction after six sessions.

The study found that sensory aspects of pain decreased more significantly than emotional aspects, suggesting that biofeedback may be particularly effective in addressing the physical sensations associated with PLP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biofeedback in the treatment of phantom limb pain: a time-series analysis. Harden, RN., Houle, TT., Green, S., et al.[2019]

Training with a brain-computer interface (BCI) to control a virtual hand significantly reduced phantom limb pain in 12 patients over a 3-day period, with pain levels decreasing by 32% and 36% at follow-ups on days 4 and 8, respectively.

The reduction in pain was statistically significant compared to a control training that involved random movements, indicating that the BCI training was effective in alleviating phantom limb pain for at least one week after the intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BCI training to move a virtual hand reduces phantom limb pain: A randomized crossover trial. Yanagisawa, T., Fukuma, R., Seymour, B., et al.[2020]

Chronic pain syndromes, such as fibromyalgia and chronic back pain, involve not only heightened pain perception but also changes in how the brain processes sensory and motor information, which can affect treatment outcomes.

Therapeutic approaches like sensorimotor training and behavioral therapy, including operant behavioral therapy and mirror training, show promise in improving pain management by addressing both pain perception and the interaction between pain and reward mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chronic pain : Perception, reward and neural processing]. Becker, S., Diers, M.[2018]

Psychological interventions that target maladaptive memory processes are effective in managing phantom limb pain, highlighting the importance of addressing the brain's learning and memory aspects in pain syndromes.

Recent techniques like sensory discrimination training, mirror treatment, and virtual reality training not only alleviate phantom limb pain but also help reverse harmful changes in the brain associated with the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phantom limb pain. Psychological treatment strategies]. Diers, M., Flor, H.[2021]

In a study with 21 participants using fMRI, operant conditioning was found to significantly reduce pain ratings more than classical conditioning when exposed to high pain stimuli, indicating its potential efficacy in pain modulation.

Neural activity in the brain showed that operant conditioning activated the temporoparietal junction more than classical conditioning, while also reducing activity in the primary somatosensory cortex during pain, suggesting different underlying mechanisms for these two types of learning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Operant and classical learning principles underlying mind-body interaction in pain modulation: a pilot fMRI study. Lee, IS., Jung, WM., Lee, YS., et al.[2021]

Citations

1. withpower.com withpower.com/trial/phase-phantom-limb-7-2023-aa141

Operant Conditioning for Phantom Limb Pain Research shows that biofeedback, a component of operant conditioning, can reduce phantom limb pain by 20-30% in some patients. Additionally, brain-computer ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7455320/

BCI training to move a virtual hand reduces phantom limb ... VAS scores were significantly reduced by 32% at day 4 after real training but not after random training. Pain was also significantly reduced by 36% at day 8 ...

3. clinsurggroup.us clinsurggroup.us/articles/OJPM-7-135.pdf

Brain-computer interface applications to decrease phantom ... Finally, it is established that phantom limb pain research benefits from incorporating brain-computer interfaces as part of non-pharmaceutical ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05880251/operant-conditioning-of-sensory-brain-responses-to-reduce-phantom-limb-pain-in-people-with-limb-amputation

Operant Conditioning of Sensory Brain Responses to ... The study will investigate the application of a non-pharmacological operant conditioning approach to reduce phantom limb pain (PLP).

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10992984/

Is Phantom Limb Awareness Necessary for the Treatment of ... The 3-day training using a BCI reduced phantom limb pain by approximately 30%, and the analgesic effects continued for approximately five days. The pain ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9197102/

Home-Based EEG Neurofeedback Intervention for the ... This study was designed to assess the efficacy and safety of a novel home-based NFB device for managing chronic pain by modifying specific EEG activity.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00731614

Cognitive Behavior Therapy (CBT) and Mirror Training for ... The goal of this study is to test whether a combination of cognitive-behavior therapy and mirror training reduces phantom limb pain for veterans with ...