Symptoms and General Pathology

All Conditions

Nervous System Diseases

Behaviors and Mental Disorders

Neoplasms

Rare Diseases

Pain, Postoperative

Chronic Pain

Pain

Phantom Limb

Acute Pain

Neuroma

Postoperative Complications

Neurologic Manifestations

Perceptual Disorders

Neurobehavioral Manifestations

Nerve Sheath Neoplasms

Neoplasms, Nerve Tissue

Neoplasms by Histologic Type

Chronic Graft Versus Host Disease

Acute Graft Versus Host Disease

Standard medical therapy and 30 to 60 days of peripheral nerve stimulation starting within 7 days after surgery

Up to 60 days of peripheral nerve stimulation

Peripheral nerve stimulation

Medications, physical therapy, or other pain treatments

Standard Medical Therapy

Denise Lester, MD

Limb loss is frequently associated with postamputation pain that can be challenging to treat and often involves opioids. Advances in the field of neuromodulation has led to development of an intentionally reversible percutaneous peripheral nerve stimulation (PNS) system that has had promising results when treating chronic postamputation pain. PNS may offer sustained pain relief even after the treatment period has ended. Currently, there is no convincing evidence regarding the role of PNS in the acute postoperative period, which may be a critical time to control pain as those with higher pain appear to be at higher risk for developing persistent post-procedural pain. The investigators of this study aim to evaluate the feasibility and effects of PNS in the acute postoperative period and determine the feasibility of completing a randomized controlled treatment outcome study.

16 patients with new nontraumatic transfemoral or transtibial amputation will be enrolled in the study

Having met inclusion criteria, the patients will be randomized to experimental or control groups

Patients in the experimental group undergo placement of PNS leads within 7 days of amputation surgery

Patients in both groups will be treated with standard pharmacologic and nonpharmacologic pain therapies and evaluated weekly for 8 weeks, then at 3, 6, and 12 months postamputation

Postoperative Peripheral Nerve Stimulation for Management of Post-amputation Pain

Effects of Postoperative Percutaneous Peripheral Nerve Stimulation on Acute and Chronic Amputation Pain

Using the Brief Pain Inventory-Short Form (BPI-SF) questionnaire, subjects were asked to rate their PLP over the past 24 hours on a scale of "0"=no pain to "10"=worst pain they have ever experienced. A lower score is better. Data from Weeks 1-4 and Weeks 5-8 were averaged to obtain a numerical score for these time points.

Using the Brief Pain Inventory-Short Form (BPI-SF) questionnaire, subjects were asked to rate their RLP over the past 24 hours on a scale of "0"=no pain to "10"=worst pain they have ever experienced. A lower score is better. Data from Weeks 1-4 and Weeks 5-8 were averaged to obtain a numerical score for these time points.

The number of subjects prescribed any opioid medication and any dose. Data from Weeks 1-4 and Weeks 5-8 were averaged to obtain a numerical score for these time points.

Opioid consumption (daily OME) over time was collected for all subjects.

FIM mobility subscores were recorded by a physical therapist to measure the ability to walk, use a wheelchair, transfer to tub/shower, transfer to toilet, and mobility in bed, chair, and wheelchair. Scores range from "1" = subject requires total assistance for the task to "7" = complete independence. A higher score is better.

Using the Brief Pain Inventory-Short Form (BPI-SF) questionnaire, subjects were asked to rate how much pain has interfered with daily activities over the past 24 hours on a scale of "0" = no interference to "10" = completely interferes with activities. A lower score is better.

Self-report measure PGIC reflects a patient's belief about the efficacy of treatment. PGIC is a 7 point scale depicting a patient's rating of overall improvement. Patients rate their change as

1 = "very much improved," 2 = "much improved," 3 = "minimally improved," 4 = "no change," 5 = "minimally worse," 6 = "much worse," or 7 = "very much worse." A lower score is better.

Pain catastrophizing is the tendency to magnify the threat value of a pain stimulus and to feel helpless in the presence of pain. This is further characterized by the inability to prevent or inhibit pain-related thoughts surrounding a painful event. Pain catastrophizing affects how individuals experience pain. The PCS is a 13-item inventory of statements in which the subject is asked to rate the degree to which they agree, on a scale of "0" = not at all to "4" = all the time. The responses for each item are added for a total PCS score (range 0-52). A lower score is better.

The PDI is designed to measure the degree to which aspects of life are disrupted by chronic pain. The impact of pain on various aspects of life (e.g. family/home responsibilities, recreation, social activity, occupation, sexual behavior, self-care, and life-support activities) are recorded on a 10-point scale from "0" = no disability to "10" = worst disability. The sum of scores is recorded for a total PDI score (range 0-70). A lower score is better.

Percent of Group that was readmitted to the hospital within 30 days following hospital discharge.

Hospital LOS was calculated from day of surgery to day of discharge from inpatient hospital ward to rehabilitation facility.

Hunter Holmes Mcguire Veteran Affairs Medical Center

Subjects in the Control Group were not at risk for PNS Lead Reimplantation because they did not undergo implantation of any peripheral nerve stimulator leads. Other \[Not Including Serious\] Adverse Events were not monitored/assessed in the Control Arm/Group.

Up to 60 days of PNS starting within 7 days after major lower limb amputation surgery. Subjects also received standard medical therapy (SMT). SMT is defined as pharmacotherapy, physical therapy, or other therapies.

Peripheral Nerve Stimulation (PNS)

Subjects received SMT only after major lower limb amputation surgery. SMT is defined as pharmacotherapy, physical therapy, or other therapies.

Control

Total

Age, Categorical

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

United States

Region of Enrollment

Perineural Catheter Infusion

Taking Opioids Preoperatively

Level of Amputation

Indication for Surgery

Several participants underwent unanticipated amputation revisions, which has the potential to contribute to worsening pain and the need for increased opioids, which may significantly confound results. Subjects were instructed to use the device continuously, and the effects of PNS therapy may be impacted by the number of hours the device was utilized by the patient. Variations in subject compliance with device usage may impact outcomes.

Dr. Denise Lester

Baseline

Weeks 1-4

Weeks 5-8

Month 3

Subjects who completed up to 60 days of peripheral nerve stimulation (PNS) and standard medical therapy (SMT) or (SMT) only.

Average Phantom Limb Pain (PLP) Score

Average Residual Limb Pain (RLP) Score

Worst Phantom Limb Pain (PLP) Score

Worst Residual Limb Pain (RLP) Score

Best Phantom Limb Pain (PLP) Score

Best Residual Limb Pain (RLP) Score

Hospital Discharge

Week 12

Between Weeks 1-4 and Weeks 5-8, three subjects in the PNS Group terminated due to unrelated medical events (2) or withdrew consent (1). After Week 12, two subjects in the Control Group terminated due to unrelated medical events or withdrew consent (data for one subject was collected prior to withdrawal).

Number Taking Opioids

Preop

Average Oral Morphine Equivalents (OME)

Walk (Preop)

Walk (Week 4)

Walk (Week 8)

Wheelchair (Preop)

Wheelchair (Week 4)

Wheelchair (Week 8)

Tub/Shower Transfer (Preop)

Tub/Shower Transfer (Week 4)

Tub/Shower Transfer (Week 8)

Toilet Transfer (Preop)

Toilet Transfer (Week 4)

Toilet Transfer (Week 8)

Bed/Chair/Wheelchair Mobility (Preop)

Bed/Chair/Wheelchair Mobility (Week 4)

Bed/Chair/Wheelchair Mobility (Week 8)

Functional Independence Measure (FIM) Scores

Week 4

Week 8

Subjects who were enrolled in the study and for whom this data was collected.

Pain Interference

Patient Global Impression of Change (PGIC)

Pain Catastrophizing Scale (PCS)

Pain Disability Index (PDI)

30-day Readmission Rate

Hospital Length of Stay (LOS)

Standard medical therapy and 30 to 60 days of peripheral nerve stimulation starting within 7 days after surgery

Peripheral nerve stimulation: Up to 60 days of peripheral nerve stimulation

Standard Medical Therapy: Medications, physical therapy, or other pain treatments

Standard medical therapy only

Standard Medical Therapy: Medications, physical therapy, or other pain treatments

Standard Medical Therapy (SMT)

Overall Study

Wounds and Injuries

Immune System Diseases

Eye Diseases

Heart and Blood Diseases

Skin and Connective Tissue Diseases

Nutritional and Metabolic Diseases

Alzheimer Disease

Parkinson Disease

Lewy Body Disease

Spinal Cord Injuries

Paralysis

Myasthenia Gravis

Atrophy

Tremor

Essential Tremor

Supranuclear Palsy, Progressive

Multiple System Atrophy

Shy-Drager Syndrome

Syndrome

Parkinsonian Disorders

Ganglion Cysts

Synovial Cyst

Basal Ganglia Diseases

Brain Diseases

Central Nervous System Diseases

Movement Disorders

Synucleinopathies

Neurodegenerative Diseases

Dementia

Tauopathies

Neurocognitive Disorders

Mental Disorders

Psychotic Disorders

Spinal Cord Diseases

Trauma, Nervous System

Paraneoplastic Syndromes

Paraneoplastic Syndromes, Nervous System

Nervous System Neoplasms

Autoimmune Diseases

Autoimmune Diseases of the Nervous System

Neuromuscular Junction Diseases

Neuromuscular Diseases

Autonomic Nervous System Diseases

Primary Dysautonomias

Hypotension

Vascular Diseases

Ophthalmoplegia

Ocular Motility Disorders

Cranial Nerve Diseases

Familial Alzheimer Disease

Progressive Supranuclear Palsy

Anti-Infective Agents

Central Nervous System Depressants

All Drugs and Chemicals

Ethanol

Phenylethyl Alcohol

Non-smokers, ages 18-80, diagnosed with Parkinson's Disease. Must be Hoehn and Yahr stage 2 or less with a history of motor symptoms less than two years.

Non-smokers, ages 18-80, diagnosed with Alzheimer's Disease. Must meet the 2011 National Institute on Aging-Alzheimer's Association and the 1984 National Institute for Neurological and Communicative Disorders and Stroke-Alzheimer's disease and Related Disorders Association criteria for probable AD.

Non-smokers, ages 18-80, diagnosed with Progressive Supranuclear Palsy. Must meet the NINDS-SPSP criteria for probable PSP, which requires vertical supranuclear gaze palsy, prominent postural instability, and falls in the first year of onset, as well as a number of other clinical features.

Non-smokers, ages 18-80, diagnosed with Essential Tremor.

Non-smokers, ages 18-80, diagnosed with Drug-Induced Parkinson's Disease.

Non-smokers, ages 18-80, diagnosed with Myasthenia Gravis.

Non-smokers, ages 18-80, who have been diagnosed with Multiple System Atrophy.

Non-smokers, ages 18-80, diagnosed with Diffuse Lewy Body Disease. Must meet the Consensus Criteria for the clinical diagnosis of DLBD.

Non-smokers, ages 18-80, with no neurodegenerative disease, and no first-degree relatives with a neurodegenerative disease.

Eye blink responses will be induced using standard stimulating electrodes employed in surface electromyography (EMG). The subjects will recline with their eyes gently closed. Sticky electrodes will be placed to the left and below the left eye. 6 different facial regions will be stimulated. The electrical stimulation will be kept constant during the test sessions. To prevent habituation, the stimuli will be delivered randomly at intervals of 45-60 sec. Four 0.2 msec pulses will be presented. In some cases, paired pulse stimulation will be performed, and a conditioning stimulus will be applied to the target facial regions at the following intervals: 10, 200, 400, 600 and 800 msec. 4 pulses will be presented at each stimulus interval with randomized interval and pulse sequences.

Electrical Brainstem Responses

Olfactory testing will be performed using standard tests. The University of Pennsylvania Smell Identification Test (UPSIT) assesses a subjects ability to identify odors in a forced choice format. The Snap and Sniff Threshold Test provides a threshold measure of phenyl ethyl alcohol. Short-term odor memory will be assessed using a standardized 12-item four-alternative forced-choice Odor Memory Test. This non-lexical test employs 10-, 30-, and 60-second delay intervals between the presentation of the target odorant and the first of four successively presented odors from which the target is to be selected.

Olfactory Tests

During a 2-hour visual deprivation period, subjects will wear comfortable light-tight goggles with lenses that have been blackened by flat black paint. Subjects will be given the opportunity to recline comfortable in a padded reclining chair during this time.

Visual Deprivation

Electrical stimulation will be applied to a nerve of your arm. Sticky electrode pads will also be placed on a hand muscle. You will receive electrical stimulations that lasts less than a second. The stimulations will make your muscle twitch.

Peripheral Nerve Stimulation

Richard L Doty, PhD

This study seeks to establish the sensitivity and specificity of what appears to be a unique brainstem biomarker of Parkinson's Disease (PD) - an electrically induced olygosynaptic nasotrigeminal reflex response - in differentiating early stage PD from normal controls and from patients with various other neurodegenerative diseases. This study will additionally compare the biomarker to olfactory testing.

Parkinson's disease (PD), a devastating age-related disease that is clinically defined by its effects on the motor system, afflicts more than six million people worldwide, imposing enormous burdens on patients, relatives, caretakers, and society in general. Diagnostic errors are common, particularly as symptoms first arise. The most common misdiagnoses are Alzheimer's disease (AD), essential tremor, and vascular pseudo-Parkinson's Disease. An accurate diagnosis is typically made at a later stage of the disease when marked and irreversible damage has occurred within the motor control system of the brain. Sensitive and specific biomarkers of the early stages of PD are urgently needed. Identification of such markers is critical for the development and assessment of medications and other interventions designed to eliminate or reduce the gradual and irreversible decline of neurons involved in the disorder. This study seeks to establish the sensitivity and specificity of what appears to be a unique brainstem biomarker of PD - an electrically induced trigeminal nerve blink reflex response - in differentiation of early stage PD from normal controls and such neurodegenerative diseases as early stage AD, progressive supranuclear palsy (PSP), and diffuse Lewy Body disease (DLBD). This study will additionally compare the biomarker to olfactory test results.

Biomarkers in Neural Disorders

Latency, amplitude, and area under the curve of electrical brainstem reflex response of trigeminal nerve branches measured on the face musculature (before and after short-term visual deprivation).

The number of correct odor identification responses out of 40 from the standardized University of Pennsylvania Smell Identification Test (before and after short-term visual deprivation).

The number of correct responses in picking out an odor previously presented from three foils 10, 30, and 60 sec later using the standardized Odor Detection/Discrimination Test (before and after short-term visual deprivation).

The average of 7 reversals in a staircase odor detection threshold test that employs phenyl ethyl alcohol (rose oil) concentrations ranging from -7 to -2 log dilutions in light mineral oil.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Postoperative Peripheral Nerve Stimulation for Management of Post-amputation Pain	NCT03484429	Phantom Limb Pa... Postoperative P... Neuroma Acute Pain Chronic Pain Residual Limbs Amputation	Peripheral nerv... Standard Medica...	18 Years -	Hunter Holmes Mcguire Veteran Affairs Medical Center
Biomarkers in Neural Disorders	NCT02761707	Parkinson's Dis... Alzheimer's Dis... Progressive Sup... Essential Tremo... Multiple System... Drug Induced Pa... Diffuse Lewy Bo... Myasthenia Grav... Spinal Cord Inj...	Electrical Brai... Olfactory Tests Visual Deprivat... Peripheral Nerv...	18 Years - 80 Years	University of Pennsylvania
Postoperative Peripheral Nerve Stimulation for Management of Post-amputation Pain	NCT03484429	Phantom Limb Pa... Postoperative P... Neuroma Acute Pain Chronic Pain Residual Limbs Amputation	Peripheral nerv... Standard Medica...	18 Years -	Hunter Holmes Mcguire Veteran Affairs Medical Center
Postoperative Peripheral Nerve Stimulation for Management of Post-amputation Pain	NCT03484429	Phantom Limb Pa... Postoperative P... Neuroma Acute Pain Chronic Pain Residual Limbs Amputation	Peripheral nerv... Standard Medica...	18 Years -	Hunter Holmes Mcguire Veteran Affairs Medical Center

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