Operant Conditioning of Sensory Brain Responses to Reduce Phantom Limb Pain in People With Limb Amputation

NCT05880251 | Completed

• 2 other identifiers: F4410-P1I21RX004410-01A1
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Phantom Limb Pain After Amputation; Upper Limb Amputation; Phantom Pain; Chronic Pain; Lower Limb Amputation

Keywords

Phantom limb pain; Amputation; Operant Conditioning; Brain-Computer Interface; Electroencephalography; Tactile sense; Instrumental learning; Event Related Potentials

Outcome Measures

Primary Outcomes (3)

• Change in Pain as Measured by the Short form-McGill Pain Questionnaire (SF-MPQ)

  The Sf-MPQ assesses the pain quality in the sensory (11 items) and affective (4 items) dimensions. Each item is rated on an intensity scale of 0 (none) to 3 (severe). Total score is obtained by summing the scores for all items and the range is 0 (no pain) to 45 (severe pain).

  Baseline, end of training (session 20) i.e. approximately 10 weeks from baseline, follow-up at 3-months after training ends, follow-up at 6-months after training ends

• Change in Evoked Potential (EP) Amplitude and threshhold

  The evoked response to tactile stimuli will be captured in one of two ways 1) EMG and Reflex evoke responses from cutaneous nerve on the residual Limb and 2) With 64 channel non-invasive scalp electroencephalography (EEG) electrodes placed on the scalp. SSEP will be assessed at the sensorimotor cortex contralateral to the amputated limb. An increase in amplitude will indicate improvement in the sensorimotor response and tolerance.

  Baseline, end of training (session 20) i.e. approximately 10 weeks from baseline, follow-up at 3-months after training ends, follow-up at 6-months after training ends

• Change in Somatosensory Evoked Potential (SSEP) Latency as Measured by a Tactile Event Related Potential Test

  The evoked response to tactile stimuli will be captured with 64 channel non-invasive scalp electroencephalography (EEG) electrodes placed on the scalp. SSEP will be assessed at the sensorimotor cortex contralateral to the amputated limb. A reduction in latency will indicate improvement in the sensorimotor cortical response.

  Baseline, end of training (session 20) i.e. approximately 10 weeks from baseline, follow-up at 3-months after training ends, follow-up at 6-months after training ends

Secondary Outcomes (1)

• Change in Impact of Pain on Quality of Life as Measured by the West Haven-Yale Multidimensional Pain Inventory (WHYMPI)

  Baseline, end of training (session 20) i.e. approximately 10 weeks from baseline, follow-up at 3-months after training ends, follow-up at 6-months after training ends

Study Arms (2)

Intervention Group

EXPERIMENTAL

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

Behavioral: Operant Conditioning with Peripheral Stimulation

Control Group

EXPERIMENTAL

Control group receives peripheral stimulation but without operant conditioning feedback.

Behavioral: Control Group with Peripheral Stimulation Only

Interventions

Operant Conditioning with Peripheral Stimulation BEHAVIORAL

This is a training intervention to strengthen the weakened sensorimotor responses and reduce pain, after a limb amputation. Non-painful peripheral stimulation will be applied to elicit a response.

Intervention Group

Control Group with Peripheral Stimulation Only BEHAVIORAL

This is a control intervention in which the non-painful peripheral stimulation will be applied, same as the operant conditioning group, but no training feedback will be provided.

Control Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• An upper (or lower limb) amputation more than 6 months ago, that has produced a moderate to severe hand/arm (or foot/leg) phantom limb pain,
• Male or female age 18 years or older,
• Medical clearance to participate,
• Reasonable expectation that ongoing medications, if any, will be maintained without change for at least 4 months from the start of the study,
• Able to provide informed consent and to understand the study instructions,
• Able to participate in the specific study procedures.

You may not qualify if:

• Presence of other medically unstable and/or infectious condition (e.g., uncontrolled diabetes with recent weight loss, diabetic coma, frequent insulin reactions),
• A cardiac condition (e.g., history of myocardial infarction or congestive heart failure),
• Cognitive and/or attention difficulties affecting participant's ability to follow study directions,
• Known skin disorders or damaged skin at the anticipated at the scalp for EEG recording (e.g., unhealed wounds, broken skin).
• Metal implants above the chest

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

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

Albany, New York, 12208-3410, United States

Location

Related Publications (1)

• Thompson AK, Wolpaw JR. Operant conditioning of spinal reflexes: from basic science to clinical therapy. Front Integr Neurosci. 2014 Mar 18;8:25. doi: 10.3389/fnint.2014.00025. eCollection 2014.

  PMID: 24672441 BACKGROUND

MeSH Terms

Conditions

Phantom Limb; Chronic Pain

Interventions

Control Groups

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Pain, Postoperative; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• Jodi A Brangaccio, PT

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: * The pre and post clinical assessment will be performed by a blinded evaluator. * The participant will not be told about group assignment till the end of the last follow-up session and assessment * Investigators will keep blinded to the baseline clinical measures.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Participants are randomly assigned to 2 groups, one group receiving the operant conditioning feedback with peripheral stimulation (Intervention group) and the other receiving only peripheral stimulation with no operant conditioning feedback (Control group).

Study Record Dates

• First Submitted: May 9, 2023
• First Posted: May 30, 2023
• Study Start: July 1, 2023
• Primary Completion: July 1, 2025
• Study Completion: August 29, 2025
• Last Updated: January 16, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)