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

Trial Summary

What is the purpose of this trial?

The study will investigate the application of a non-pharmacological operant conditioning approach to reduce phantom limb pain (PLP). PLP afflicts 60-90% people who have lost a limb. It can last for years and lead to drug dependence, job loss, and poor quality of life. Current non-pharmacological interventions are encouraging but limited, and their efficacy remains unclear. Limb amputation is known to lead to abnormal sensorimotor reorganization in the brain. Multiple studies have shown that PLP severity is correlated with the extent of this reorganization. The current study will train participants via realtime feedback of brain responses to promote more normal sensorimotor response, with the goal to reduce phantom limb pain.

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 data supports the effectiveness of the treatment 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 interface training and neurofeedback have been shown to modulate pain by altering brain activity related to phantom limb sensations. ^{1 2 3 4 5}

Is operant conditioning therapy safe for humans?

The research does not provide specific safety data for operant conditioning therapy, but it is generally used in chronic pain management and psychological treatments, suggesting it is considered safe in these contexts. ^{4 6 7 8 9}

How is Operant Conditioning with Peripheral Stimulation different from other treatments for phantom limb pain?

Operant Conditioning with Peripheral Stimulation is unique because it uses a learning-based approach to modify brain activity and reduce pain, unlike traditional treatments that focus on managing symptoms. This therapy involves actively engaging the brain's learning processes to change how pain is perceived, which can lead to long-term relief by reversing maladaptive brain changes associated with phantom limb pain. ^{1 4 7 8 9}

Research Team

Jodi A Brangaccio, PT

Principal Investigator

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

Eligibility Criteria

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

I am 18 years old or older.

Medical clearance to participate

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[Chronic pain : Perception, reward and neural processing]. [2018]

2. Germany pubmed.ncbi.nlm.nih.gov

Biofeedback in the treatment of phantom limb pain: a time-series analysis. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

BCI training to move a virtual hand reduces phantom limb pain: A randomized crossover trial. [2020]

4. Germany pubmed.ncbi.nlm.nih.gov

[Phantom limb pain. Psychological treatment strategies]. [2021]

5. United States 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. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Operant learning theory in pain and chronic pain rehabilitation. [2021]

7. England 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. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

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

9. England pubmed.ncbi.nlm.nih.gov

Operant and classical learning principles underlying mind-body interaction in pain modulation: a pilot fMRI study. [2021]