PTP-NP: Improving Functions in Veterans With Post-traumatic Peripheral Neuropathic Pain

• Sponsor: VA Office of Research and Development (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT02979925
• Collaborator: (none)
• Enrollment: 57
• Location: 1
• Arms: 2
• Actual Duration (Months): 34.9
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

The proposed study will set the foundation for future multi-center studies. To validate tMS as a non-contact and non-invasive pain treatment option for reducing pain in Veterans with PTP-NP and improving their overall functions.

Condition or Disease	Intervention/Treatment	Phase
Neuropathic Pain	Device: Active Transcutaneous Magnetic Stimulation; Device: Sham Transcutaneous Magnetic Stimulation	N/A

Detailed Description

This study will only be conducted at the VA hospital in San Diego.

Study Design

• Study Type: Interventional
• Actual Enrollment: 57 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Improving Functions in Veterans With Post-Traumatic Peripheral Neuropathic Pain
• Actual Study Start Date: Nov 1, 2016
• Actual Primary Completion Date: Sep 30, 2019
• Actual Study Completion Date: Sep 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active transcutaneous magnetic stimulation Active transcutaneous magnetic stimulation (TMS) at the target site of nerve damage/injury.	Device: Active Transcutaneous Magnetic Stimulation; Active transcutaneous magnetic stimulation (TMS) at the target site of nerve damage/injury.; Other Names: TMS
Sham Comparator: Sham transcutaneous magnetic stimulation Sham TMS will consist of the same parameters as active, however, the subject will be shielded from the magnetic field of the coil.	Device: Sham Transcutaneous Magnetic Stimulation; Sham TMS will consist of the same parameters as active, however, the subject will be shielded from the magnetic field of the coil.; Other Names: TMS

Outcome Measures

Primary Outcome Measures

1. Evaluation of Spontaneous Pain Scores [Assessed during each of the subject's baseline visit, 1 week post treatment visit, and 4 weeks post treatment visit.]

   Spontaneous pain rating: Spontaneous pain level will be measured by using a sliding algometer, known as the Mechanical Visual Analog Scale (M-VAS). The device has been well validated, and is anchored at the left by "no pain sensation" and at the right by "the most intense pain sensation imaginable." The corresponding length of the red bar with a scale from 0 to 100, which can be read on the back by the tester, represents the subject's intensity of pain. 0 represents "no pain sensation" and 100 represents "the most intense pain sensation imaginable." A lower value indicates a better outcome with lower levels of pain reported.

Secondary Outcome Measures

1. Evaluation of Evoked Pain Scores: Stroking [Assessed during each of the subject's baseline visit, 1 week post treatment visit, and 4 weeks post treatment visit.]

   Stroking evoked pain will be assessed by gently moving a paintbrush over the site of PTNP. The patients will be asked if pain is felt. If so, the intensity of pain will be rated on a scale known as the Mechanical Visual Analog Scale (M-VAS). The device has been well validated, and is anchored at the left by "no pain sensation" and at the right by "the most intense pain sensation imaginable." The corresponding length of the red bar with a scale from 0 to 100, which can be read on the back by the tester, represents the subject's intensity of pain. 0 represents "no pain sensation" and 100 represents "the most intense pain sensation imaginable." A lower value indicates a better outcome with lower levels of pain reported.

2. Evaluation of Evoked Pain Scores: Von Frey [Assessed during each of the subject's baseline visit, 1 week post treatment visit, and 4 weeks post treatment visit.]

   Punctate evoked pain will be conducted by gently pressing a 5.18 von Frey monofilament against the site of PTNP. The patients will be asked if pain is felt. If so, the intensity of pain will be rated on a scale known as the Mechanical Visual Analog Scale (M-VAS). The device has been well validated, and is anchored at the left by "no pain sensation" and at the right by "the most intense pain sensation imaginable." The corresponding length of the red bar with a scale from 0 to 100, which can be read on the back by the tester, represents the subject's intensity of pain. 0 represents "no pain sensation" and 100 represents "the most intense pain sensation imaginable." A lower value indicates a better outcome with lower levels of pain reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study

• Subject is willing and able to comply with scheduled visits, treatment plan, daily pain, sleep and all study related assessments and procedures

• Subjects must be literate in the language used in the assessments and pain diary

• Veterans (men or women) of any race or ethnicity who are at least 18 years of age

• Female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 7 days after the last session of the assigned treatment

• A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active

• Subject must have chronic peripheral neuropathic pain present for more than 4 months after a traumatic or surgical event per medical history, this may include, for example:

• motor vehicle accident

• fall

• sports injury

• knee or hip replacement

• hernia repair

• thoracotomy

• mastectomy

• focal/localized burns or crush injury

• In addition, to be eligible for inclusion in the study, all subjects must:

• have an average daily Numerical Pain Rating Scale (NPRS) score >3 during B1; and

• have a spontaneous pain intensity >30 on 0-100 Mechanical Visual Analogue Scale (M-VAS) to be eligible for randomization

• Must have their implicated peripheral nerve(s) identified

• Must meet criteria for neuropathic pain assessment to meet eligibility for the study [46]. Pain distribution across a nerve territory and history indicates relevant lesion or disease plus criteria listed in a and/or b

• (A): At least one negative or positive sensory sign or symptom confined to innervation territory of the lesioned nervous structure. Examples of negative or positive signs or symptoms include:

• Burning, stabbing or tingling sensation/pain

• Numbness/paresthesia

• Cold, heat or pressure

• Hyperalgesia or allodynia

• Hypoesthesia

• Increased or decreased sharp sensation (e.g., pinprick testing)

• Decreased vibration/vibratory sensation

• (B): Prior diagnostic tests confirming lesion or disease explaining neuropathic pain (Nerve conduction studies, EMG, skin or nerve biopsy). Documentation of affected nerve(s) indicating that the subject's pain is of neuropathic origin and is a result of injury/trauma to the affected/implicated nerve(s).

Exclusion Criteria:

Subjects presenting with ANY of the following will NOT be included in the study:

• Subjects with neuropathic pain due to:

• diabetic peripheral neuropathy

• post herpetic neuralgia

• Human Immunodeficiency Virus

• chemo/anti-viral therapy

• trigeminal neuralgia

• carpal tunnel syndrome

• subjects whose post-traumatic neuropathic pain is categorized as central (e.g., spinal cord injury) rather than peripheral

• Subjects with pain due to Complex Regional Pain Syndrome (CRPS, Type I or Type II)

• Phantom limb pain after amputation. However, subjects with stump pain and phantom sensation but no phantom pain will not be excluded

• Subjects with skin conditions in the affected dermatome that in the judgment of the investigator can interfere with evaluation of the neuropathic pain condition

• Subjects with other pain such as lumbar or cervical radiculopathy that may confound assessment or self-evaluation of the peripheral neuropathic pain

• subjects with significant somatic pain at the site of their trauma that may confound assessment or self-evaluation of their neuropathic pain

• Any subject considered at risk of suicide or self-harm based on investigator judgment and/or the details of a risk assessment

• Use of prohibited medications in the absence of appropriate washout periods

• Participation in any other clinical trial within the 30 days prior to screening and/or during participation in this study

• Subjects with a history of a cardiac arrhythmia that has led to the placement of a cardiac pacer or defibrillator will be excluded from the study

• Pregnant females and females of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception during the study

• Subjects with a current diagnosis of DSM-IV-TR Axis I disorder, including, for example:

• schizophrenia

• bipolar disorder

• other psychotic disorders such as schizoaffective disorder and delusion disorder

• somatoform disorders or factitious disorders

• bipolar disorders, even if controlled or stable

• alcohol or substance related disorders in the past 2 years

• however, diagnoses of Generalized Anxiety Disorder (GAD) or major depression (MDD) that is clinically stable are allowed

• Subjects with pending Worker's Compensation, Worker's Compensation, civil litigation or disability claims pertinent to the subject based upon trauma

• current involvement in out-of-court settlements for claims pertinent to subject's trauma

• subjects with fully resolved litigation and compensation claims can participate

• Subjects who have previously received either transcranial or transcutaneous magnetic stimulation therapy in the past

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA San Diego Healthcare System, San Diego, CA	San Diego	California	United States	92161

Sponsors and Collaborators

• VA Office of Research and Development

Investigators

• Principal Investigator: Albert Yick Leung, MD, VA San Diego Healthcare System, San Diego, CA

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 7, 2015

More Information

Publications

None provided.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT02979925
• Other Study ID Numbers: B2366-P; 1192133
• First Posted: Dec 2, 2016
• Last Update Posted: Jul 12, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by VA Office of Research and Development: neuropathic pain; TMS; nerve injury; transcutaneous magnetic stimulation
• Additional relevant MeSH terms: Neuralgia

Study Results

Participant Flow

Recruitment Details	Participants were recruited from October 2016 to June 2018 at the VA San Diego Medical Center.

Arm/Group Title	Active Transcutaneous Magnetic Stimulation	Sham Transcutaneous Magnetic Stimulation
Arm/Group Description	Active transcutaneous magnetic stimulation (tMS) at the target site of nerve damage/injury. Active Transcutaneous Magnetic Stimulation: Active transcutaneous magnetic stimulation (tMS) at the target site of nerve damage/injury.	Sham tMS will consist of the same parameters as active, however, the subject will be shielded from the magnetic field of the coil. Sham Transcutaneous Magnetic Stimulation: Sham tMS will consist of the same parameters as active, however, the subject will be shielded from the magnetic field of the coil.
Period Title: Overall Study
STARTED	28	29
COMPLETED	28	23
NOT COMPLETED	0	6

Baseline Characteristics

Arm/Group Title	Active Transcutaneous Magnetic Stimulation	Sham Transcutaneous Magnetic Stimulation	Total
Arm/Group Description	Active transcutaneous magnetic stimulation (tMS) at the target site of nerve damage/injury. Active Transcutaneous Magnetic Stimulation: Active transcutaneous magnetic stimulation (tMS) at the target site of nerve damage/injury.	Sham tMS will consist of the same parameters as active, however, the subject will be shielded from the magnetic field of the coil. Sham Transcutaneous Magnetic Stimulation: Sham tMS will consist of the same parameters as active, however, the subject will be shielded from the magnetic field of the coil.	Total of all reporting groups
Overall Participants	28	23	51
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.11 (17.02)	50.78 (14.04)	52.61 (15.68)
Sex: Female, Male (Count of Participants)
Female	3 10.7%	3 13%	6 11.8%
Male	25 89.3%	20 87%	45 88.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 14.3%	7 30.4%	11 21.6%
Not Hispanic or Latino	24 85.7%	16 69.6%	40 78.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 3.6%	1 4.3%	2 3.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	5 17.9%	4 17.4%	9 17.6%
White	19 67.9%	14 60.9%	33 64.7%
More than one race	2 7.1%	1 4.3%	3 5.9%
Unknown or Not Reported	1 3.6%	3 13%	4 7.8%
Region of Enrollment (Count of Participants)
United States	28 100%	23 100%	51 100%
Spontaneous Pain Score (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	53.52 (21.01)	49.13 (22.61)	50.44 (22.69)

Outcome Measures

1. Primary Outcome

Title	Evaluation of Spontaneous Pain Scores
Description	Spontaneous pain rating: Spontaneous pain level will be measured by using a sliding algometer, known as the Mechanical Visual Analog Scale (M-VAS). The device has been well validated, and is anchored at the left by "no pain sensation" and at the right by "the most intense pain sensation imaginable." The corresponding length of the red bar with a scale from 0 to 100, which can be read on the back by the tester, represents the subject's intensity of pain. 0 represents "no pain sensation" and 100 represents "the most intense pain sensation imaginable." A lower value indicates a better outcome with lower levels of pain reported.
Time Frame	Assessed during each of the subject's baseline visit, 1 week post treatment visit, and 4 weeks post treatment visit.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Transcutaneous Magnetic Stimulation	Sham Transcutaneous Magnetic Stimulation
Arm/Group Description	Active transcutaneous magnetic stimulation (tMS) at the target site of nerve damage/injury. Active Transcutaneous Magnetic Stimulation: Active transcutaneous magnetic stimulation (tMS) at the target site of nerve damage/injury.	Sham tMS will consist of the same parameters as active, however, the subject will be shielded from the magnetic field of the coil. Sham Transcutaneous Magnetic Stimulation: Sham tMS will consist of the same parameters as active, however, the subject will be shielded from the magnetic field of the coil.
Measure Participants	28	23
Baseline	53.52 (21.01)	49.13 (22.61)
1 week post treatment	41.41 (30.09)	46.17 (26.54)
4 weeks post treatment	38.92 (29.16)	37.52 (30.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Active Transcutaneous Magnetic Stimulation, Sham Transcutaneous Magnetic Stimulation
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.246
	Comments
	Method	Mixed Models Analysis
	Comments

2. Secondary Outcome

Title	Evaluation of Evoked Pain Scores: Stroking
Description	Stroking evoked pain will be assessed by gently moving a paintbrush over the site of PTNP. The patients will be asked if pain is felt. If so, the intensity of pain will be rated on a scale known as the Mechanical Visual Analog Scale (M-VAS). The device has been well validated, and is anchored at the left by "no pain sensation" and at the right by "the most intense pain sensation imaginable." The corresponding length of the red bar with a scale from 0 to 100, which can be read on the back by the tester, represents the subject's intensity of pain. 0 represents "no pain sensation" and 100 represents "the most intense pain sensation imaginable." A lower value indicates a better outcome with lower levels of pain reported.
Time Frame	Assessed during each of the subject's baseline visit, 1 week post treatment visit, and 4 weeks post treatment visit.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Transcutaneous Magnetic Stimulation	Sham Transcutaneous Magnetic Stimulation
Arm/Group Description	Active transcutaneous magnetic stimulation (tMS) at the target site of nerve damage/injury. Active Transcutaneous Magnetic Stimulation: Active transcutaneous magnetic stimulation (tMS) at the target site of nerve damage/injury.	Sham tMS will consist of the same parameters as active, however, the subject will be shielded from the magnetic field of the coil. Sham Transcutaneous Magnetic Stimulation: Sham tMS will consist of the same parameters as active, however, the subject will be shielded from the magnetic field of the coil.
Measure Participants	28	23
Baseline	33.55 (31.07)	24.78 (25.59)
1 week post treatment	30.74 (23.78)	20.04 (24.10)
4 weeks post treatment	26.92 (21.90)	21.35 (25.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Active Transcutaneous Magnetic Stimulation, Sham Transcutaneous Magnetic Stimulation
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.651
	Comments
	Method	Mixed Models Analysis
	Comments

3. Secondary Outcome

Title	Evaluation of Evoked Pain Scores: Von Frey
Description	Punctate evoked pain will be conducted by gently pressing a 5.18 von Frey monofilament against the site of PTNP. The patients will be asked if pain is felt. If so, the intensity of pain will be rated on a scale known as the Mechanical Visual Analog Scale (M-VAS). The device has been well validated, and is anchored at the left by "no pain sensation" and at the right by "the most intense pain sensation imaginable." The corresponding length of the red bar with a scale from 0 to 100, which can be read on the back by the tester, represents the subject's intensity of pain. 0 represents "no pain sensation" and 100 represents "the most intense pain sensation imaginable." A lower value indicates a better outcome with lower levels of pain reported.
Time Frame	Assessed during each of the subject's baseline visit, 1 week post treatment visit, and 4 weeks post treatment visit.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Transcutaneous Magnetic Stimulation	Sham Transcutaneous Magnetic Stimulation
Arm/Group Description	Active transcutaneous magnetic stimulation (tMS) at the target site of nerve damage/injury. Active Transcutaneous Magnetic Stimulation: Active transcutaneous magnetic stimulation (tMS) at the target site of nerve damage/injury.	Sham tMS will consist of the same parameters as active, however, the subject will be shielded from the magnetic field of the coil. Sham Transcutaneous Magnetic Stimulation: Sham tMS will consist of the same parameters as active, however, the subject will be shielded from the magnetic field of the coil.
Measure Participants	28	23
Baseline	53.97 (27.04)	43.13 (26.84)
1 week post treatment	46.89 (25.98)	36.22 (26.22)
4 weeks post treatment	49.27 (24.72)	38.26 (23.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Active Transcutaneous Magnetic Stimulation, Sham Transcutaneous Magnetic Stimulation
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.902
	Comments
	Method	Mixed Models Analysis
	Comments

Adverse Events

Time Frame	Adverse event data was collected from first treatment to 4 weeks after the last treatment.
Arm/Group Title	Active Transcutaneous Magnetic Stimulation		Sham Transcutaneous Magnetic Stimulation
Arm/Group Description	Active transcutaneous magnetic stimulation (tMS) at the target site of nerve damage/injury. Active Transcutaneous Magnetic Stimulation: Active transcutaneous magnetic stimulation (tMS) at the target site of nerve damage/injury.		Sham tMS will consist of the same parameters as active, however, the subject will be shielded from the magnetic field of the coil. Sham Transcutaneous Magnetic Stimulation: Sham tMS will consist of the same parameters as active, however, the subject will be shielded from the magnetic field of the coil.
All Cause Mortality
	Active Transcutaneous Magnetic Stimulation		Sham Transcutaneous Magnetic Stimulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/23 (0%)
Serious Adverse Events
	Active Transcutaneous Magnetic Stimulation		Sham Transcutaneous Magnetic Stimulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	Active Transcutaneous Magnetic Stimulation		Sham Transcutaneous Magnetic Stimulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/23 (0%)

Limitations/Caveats

One limitation of this study is small sample size. In addition, the location of nerve damage (whether it is extremities or truncal region) could be a confounding factor for the effectiveness of the treatment.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.