Neuropathic Pain in Pregnancy

NCT ID: NCT02608463

Last Updated: 2021-06-23

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-01

Study Completion Date

2019-04-19

Brief Summary

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This will be the first study to investigate the use of rTMS in the treatment of neuropathic pain in pregnancy. This study will enroll 60 pregnant subjects, age 18-45. All participants will receive treatment as usual. Subjects diagnosed with neuropathic pain will be offered rTMS as a treatment option.

Detailed Description

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Neuropathic pain is a common pain disorder that is caused by problems in the nervous system. It affects more women than men and commonly occurs in pregnancy. Physicians have little information to guide their treatment of neuropathic pain in pregnancy. The overall goal of this study is to define the course, management, and pregnancy outcomes of neuropathic pain in pregnancy and the acute postpartum period. It is difficult to manage neuropathic pain in pregnancy as treatment options must minimize their risk to the unborn child as they have a direct effect on infant outcomes through their exposure in utero. Thus, other treatments are needed. Repetitive transcranial magnetic stimulation (rTMS) may be an acceptable alternative to medications. Transcranial magnetic stimulation uses a magnetic force to change the way nerves work in the brain. This non-invasive and localized mechanism of action makes it attractive for use in special populations, such as pregnancy. Study visits will occur approximately every 4-6 weeks during pregnancy until approximately 3 months postpartum for a maximum of 12 visits.

Conditions

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Pain Pregnancy

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

All subjects will participate in Part A, receive standard of care and complete the painDETECT Questionnaire (PDQ) to be assigned to 1 of 3 groups based on the PDQ score.

Subjects in Part A will complete the following at study entry and each study visit: the Beck Depression Inventory (BDI), Visual Analogue Scale (VAS), Pain Catastrophizing Scale (PCS), and measures of pain intensity, interference, behavior. At each visit after study entry, subjects will complete the Patients' Global Impression of Change scale (PGIC); clinicians will complete the Clinical Global Impression-Global Improvement scale (CGI-I).

Subjects in Part B will receive rTMS and be followed daily until day 29 after last rTMS session. For each session, subjects will complete a VAS prior, immediately after, and 60 minutes post, day 22 \& day 29; a BDI on Days 1, 5, 12, 22, \& 29; on days 5, 12, 22, \& 29 subjects will complete the PGIC; clinicians will complete the CGI-I.
Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

NONE

Study Groups

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Part A - Neuropathic Pain

Subjects with a score of ≥ 13 on the painDETECT Questionnaire (PDQ) will be assigned to the Neuropathic Pain group.

Group Type OTHER

painDETECT Questionnaire

Intervention Type BEHAVIORAL

This self-report questionnaire consists of 7 questions that address the quality of neuropathic pain syndromes. The first 5 questions ask about the gradation of pain, question 6 asks about the pain course pattern and question 7 asks about radiating pain. There are 4 additional questions (not counted in the total score) which asks the subject to rate their pain now and over the last 4 weeks and to mark on a body chart if there is pain radiating into other parts of the body.

Pain Catastrophizing Scale

Intervention Type BEHAVIORAL

The PCS is a 13-item self-report scale. It asks subjects to reflect on past painful experiences, and to indicate the degree to which they experienced each of 13 thoughts or feelings when experiencing pain, on 5-point scales with the end points (0) not at all and (4) all the time. The PCS yields a total score and three subscale scores assessing rumination, magnification, and helplessness.

Pain Intensity Scale, Pain Interference Scale, Pain Behavior Scale

Intervention Type BEHAVIORAL

The 3-item, self-report Pain Intensity assesses how much a person hurts. The first 2 items assess pain intensity over the past 7 days; the last item asks subject to rate pain intensity "right now." The 4-item, self-report Pain Interference measures the consequences of pain on relevant aspects of subject's life. It includes impairment in subject's social, cognitive, emotional, physical, \& recreational activities. It also incorporates items about sleep and enjoyment of life. It assesses pain interference over the past 7 days.

The 7-item, self-report Pain Behavior measures behaviors that typically indicate to others that an individual is experiencing pain. Measures include observations (sighing, crying), behaviors (resting, guarding, facial expressions, asking for help), \& verbal reports of pain. It assesses pain interference over the past 7 days.

All three scales, derived from the Patient Reported Outcomes Measurement Information System (PROMIS), are not disease specific.

Beck Depression Inventory

Intervention Type BEHAVIORAL

The BDI is a widely used instrument that has been used in both clinical and non-clinical setting measuring depressive symptoms. It is a 21 item questionnaire with 4-5 responses for each question. Responses are coded 0-3 for the 4 point scales. The 5 point scales include an additional 2a and 2b response code. The symptom categories reflect overt behavioral manifestations of depression. The instrument has both a high degree of reliability and validity (Beck, Ward, Mendelson, Mock \& Erbaugh, 1961).

Visual Analogue Scale

Intervention Type BEHAVIORAL

100 mm line scale that is subject administered to subjectively rate current pain symptoms. The subject will be instructed to draw a single vertical line that best describes current state.

Patient's Global Impression of Change Scale & Clinical Global Impression-Global Improvement Scale

Intervention Type BEHAVIORAL

The PGIC gives a global rating of change in symptoms, activities, emotion, and overall quality of life related to the subject's pain condition. This is a self-rated scale.

The CGI-I gives a global rating of the improvement/change in the symptoms since the last study visit. This is administered by the MD.

Part A - Non-Neuropathic Pain

Subjects with a score of ≥ 1 or ≤ 12 on the painDETECT Questionnaire (PDQ) will be assigned to the Non-Neuropathic Pain group.

Group Type OTHER

painDETECT Questionnaire

Intervention Type BEHAVIORAL

This self-report questionnaire consists of 7 questions that address the quality of neuropathic pain syndromes. The first 5 questions ask about the gradation of pain, question 6 asks about the pain course pattern and question 7 asks about radiating pain. There are 4 additional questions (not counted in the total score) which asks the subject to rate their pain now and over the last 4 weeks and to mark on a body chart if there is pain radiating into other parts of the body.

Pain Catastrophizing Scale

Intervention Type BEHAVIORAL

The PCS is a 13-item self-report scale. It asks subjects to reflect on past painful experiences, and to indicate the degree to which they experienced each of 13 thoughts or feelings when experiencing pain, on 5-point scales with the end points (0) not at all and (4) all the time. The PCS yields a total score and three subscale scores assessing rumination, magnification, and helplessness.

Pain Intensity Scale, Pain Interference Scale, Pain Behavior Scale

Intervention Type BEHAVIORAL

The 3-item, self-report Pain Intensity assesses how much a person hurts. The first 2 items assess pain intensity over the past 7 days; the last item asks subject to rate pain intensity "right now." The 4-item, self-report Pain Interference measures the consequences of pain on relevant aspects of subject's life. It includes impairment in subject's social, cognitive, emotional, physical, \& recreational activities. It also incorporates items about sleep and enjoyment of life. It assesses pain interference over the past 7 days.

The 7-item, self-report Pain Behavior measures behaviors that typically indicate to others that an individual is experiencing pain. Measures include observations (sighing, crying), behaviors (resting, guarding, facial expressions, asking for help), \& verbal reports of pain. It assesses pain interference over the past 7 days.

All three scales, derived from the Patient Reported Outcomes Measurement Information System (PROMIS), are not disease specific.

Beck Depression Inventory

Intervention Type BEHAVIORAL

The BDI is a widely used instrument that has been used in both clinical and non-clinical setting measuring depressive symptoms. It is a 21 item questionnaire with 4-5 responses for each question. Responses are coded 0-3 for the 4 point scales. The 5 point scales include an additional 2a and 2b response code. The symptom categories reflect overt behavioral manifestations of depression. The instrument has both a high degree of reliability and validity (Beck, Ward, Mendelson, Mock \& Erbaugh, 1961).

Visual Analogue Scale

Intervention Type BEHAVIORAL

100 mm line scale that is subject administered to subjectively rate current pain symptoms. The subject will be instructed to draw a single vertical line that best describes current state.

Patient's Global Impression of Change Scale & Clinical Global Impression-Global Improvement Scale

Intervention Type BEHAVIORAL

The PGIC gives a global rating of change in symptoms, activities, emotion, and overall quality of life related to the subject's pain condition. This is a self-rated scale.

The CGI-I gives a global rating of the improvement/change in the symptoms since the last study visit. This is administered by the MD.

Part A - Control

Subjects with a score of score = 0 on the painDETECT Questionnaire (PDQ) will be assigned to the Control group.

Group Type OTHER

painDETECT Questionnaire

Intervention Type BEHAVIORAL

This self-report questionnaire consists of 7 questions that address the quality of neuropathic pain syndromes. The first 5 questions ask about the gradation of pain, question 6 asks about the pain course pattern and question 7 asks about radiating pain. There are 4 additional questions (not counted in the total score) which asks the subject to rate their pain now and over the last 4 weeks and to mark on a body chart if there is pain radiating into other parts of the body.

Pain Catastrophizing Scale

Intervention Type BEHAVIORAL

The PCS is a 13-item self-report scale. It asks subjects to reflect on past painful experiences, and to indicate the degree to which they experienced each of 13 thoughts or feelings when experiencing pain, on 5-point scales with the end points (0) not at all and (4) all the time. The PCS yields a total score and three subscale scores assessing rumination, magnification, and helplessness.

Pain Intensity Scale, Pain Interference Scale, Pain Behavior Scale

Intervention Type BEHAVIORAL

The 3-item, self-report Pain Intensity assesses how much a person hurts. The first 2 items assess pain intensity over the past 7 days; the last item asks subject to rate pain intensity "right now." The 4-item, self-report Pain Interference measures the consequences of pain on relevant aspects of subject's life. It includes impairment in subject's social, cognitive, emotional, physical, \& recreational activities. It also incorporates items about sleep and enjoyment of life. It assesses pain interference over the past 7 days.

The 7-item, self-report Pain Behavior measures behaviors that typically indicate to others that an individual is experiencing pain. Measures include observations (sighing, crying), behaviors (resting, guarding, facial expressions, asking for help), \& verbal reports of pain. It assesses pain interference over the past 7 days.

All three scales, derived from the Patient Reported Outcomes Measurement Information System (PROMIS), are not disease specific.

Beck Depression Inventory

Intervention Type BEHAVIORAL

The BDI is a widely used instrument that has been used in both clinical and non-clinical setting measuring depressive symptoms. It is a 21 item questionnaire with 4-5 responses for each question. Responses are coded 0-3 for the 4 point scales. The 5 point scales include an additional 2a and 2b response code. The symptom categories reflect overt behavioral manifestations of depression. The instrument has both a high degree of reliability and validity (Beck, Ward, Mendelson, Mock \& Erbaugh, 1961).

Visual Analogue Scale

Intervention Type BEHAVIORAL

100 mm line scale that is subject administered to subjectively rate current pain symptoms. The subject will be instructed to draw a single vertical line that best describes current state.

Patient's Global Impression of Change Scale & Clinical Global Impression-Global Improvement Scale

Intervention Type BEHAVIORAL

The PGIC gives a global rating of change in symptoms, activities, emotion, and overall quality of life related to the subject's pain condition. This is a self-rated scale.

The CGI-I gives a global rating of the improvement/change in the symptoms since the last study visit. This is administered by the MD.

Part B - rTMS

Subjects from the Neuropathic Pain group will be invited to participate in the Part B rTMS group to receive repetitive transcranial magnetic stimulation (rTMS).

Group Type EXPERIMENTAL

Beck Depression Inventory

Intervention Type BEHAVIORAL

The BDI is a widely used instrument that has been used in both clinical and non-clinical setting measuring depressive symptoms. It is a 21 item questionnaire with 4-5 responses for each question. Responses are coded 0-3 for the 4 point scales. The 5 point scales include an additional 2a and 2b response code. The symptom categories reflect overt behavioral manifestations of depression. The instrument has both a high degree of reliability and validity (Beck, Ward, Mendelson, Mock \& Erbaugh, 1961).

Visual Analogue Scale

Intervention Type BEHAVIORAL

100 mm line scale that is subject administered to subjectively rate current pain symptoms. The subject will be instructed to draw a single vertical line that best describes current state.

Patient's Global Impression of Change Scale & Clinical Global Impression-Global Improvement Scale

Intervention Type BEHAVIORAL

The PGIC gives a global rating of change in symptoms, activities, emotion, and overall quality of life related to the subject's pain condition. This is a self-rated scale.

The CGI-I gives a global rating of the improvement/change in the symptoms since the last study visit. This is administered by the MD.

Transcranial Magnetic Stimulation

Intervention Type DEVICE

Subjects will undergo daily repetitive transcranial magnetic stimulation (rTMS), defined as Monday through Friday, for a total of 10 consecutive sessions. rTMS will be applied using the NeuroStar TMS Therapy System through a figure-8 coil connected to a magnetic stimulator, which provides a biphasic pulse. The coil is applied to the primary motor cortex, M1, contralateral to the painful side. The optimal stimulus site, motor hot spot, will be determined according to visual detection of muscle twitches, and a resting motor threshold is defined as the minimal intensity necessary to induce at least one visible muscle twitch. An rTMS session consists of 10 trains at 90% intensity of resting motor threshold (one train, 100 pulses at 10 Hz; intertrain interval, 50s).

Interventions

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painDETECT Questionnaire

This self-report questionnaire consists of 7 questions that address the quality of neuropathic pain syndromes. The first 5 questions ask about the gradation of pain, question 6 asks about the pain course pattern and question 7 asks about radiating pain. There are 4 additional questions (not counted in the total score) which asks the subject to rate their pain now and over the last 4 weeks and to mark on a body chart if there is pain radiating into other parts of the body.

Intervention Type BEHAVIORAL

Pain Catastrophizing Scale

The PCS is a 13-item self-report scale. It asks subjects to reflect on past painful experiences, and to indicate the degree to which they experienced each of 13 thoughts or feelings when experiencing pain, on 5-point scales with the end points (0) not at all and (4) all the time. The PCS yields a total score and three subscale scores assessing rumination, magnification, and helplessness.

Intervention Type BEHAVIORAL

Pain Intensity Scale, Pain Interference Scale, Pain Behavior Scale

The 3-item, self-report Pain Intensity assesses how much a person hurts. The first 2 items assess pain intensity over the past 7 days; the last item asks subject to rate pain intensity "right now." The 4-item, self-report Pain Interference measures the consequences of pain on relevant aspects of subject's life. It includes impairment in subject's social, cognitive, emotional, physical, \& recreational activities. It also incorporates items about sleep and enjoyment of life. It assesses pain interference over the past 7 days.

The 7-item, self-report Pain Behavior measures behaviors that typically indicate to others that an individual is experiencing pain. Measures include observations (sighing, crying), behaviors (resting, guarding, facial expressions, asking for help), \& verbal reports of pain. It assesses pain interference over the past 7 days.

All three scales, derived from the Patient Reported Outcomes Measurement Information System (PROMIS), are not disease specific.

Intervention Type BEHAVIORAL

Beck Depression Inventory

The BDI is a widely used instrument that has been used in both clinical and non-clinical setting measuring depressive symptoms. It is a 21 item questionnaire with 4-5 responses for each question. Responses are coded 0-3 for the 4 point scales. The 5 point scales include an additional 2a and 2b response code. The symptom categories reflect overt behavioral manifestations of depression. The instrument has both a high degree of reliability and validity (Beck, Ward, Mendelson, Mock \& Erbaugh, 1961).

Intervention Type BEHAVIORAL

Visual Analogue Scale

100 mm line scale that is subject administered to subjectively rate current pain symptoms. The subject will be instructed to draw a single vertical line that best describes current state.

Intervention Type BEHAVIORAL

Patient's Global Impression of Change Scale & Clinical Global Impression-Global Improvement Scale

The PGIC gives a global rating of change in symptoms, activities, emotion, and overall quality of life related to the subject's pain condition. This is a self-rated scale.

The CGI-I gives a global rating of the improvement/change in the symptoms since the last study visit. This is administered by the MD.

Intervention Type BEHAVIORAL

Transcranial Magnetic Stimulation

Subjects will undergo daily repetitive transcranial magnetic stimulation (rTMS), defined as Monday through Friday, for a total of 10 consecutive sessions. rTMS will be applied using the NeuroStar TMS Therapy System through a figure-8 coil connected to a magnetic stimulator, which provides a biphasic pulse. The coil is applied to the primary motor cortex, M1, contralateral to the painful side. The optimal stimulus site, motor hot spot, will be determined according to visual detection of muscle twitches, and a resting motor threshold is defined as the minimal intensity necessary to induce at least one visible muscle twitch. An rTMS session consists of 10 trains at 90% intensity of resting motor threshold (one train, 100 pulses at 10 Hz; intertrain interval, 50s).

Intervention Type DEVICE

Other Intervention Names

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PDQ PCS Pain Measures BDI VAS PGIC & CGI-I NeuroStar® TMS

Eligibility Criteria

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Inclusion Criteria

* age 18-45 years old,
* ability to give informed consent,
* viable pregnancy, and
* enrollment prior or equal to 24 weeks gestation


* Subjects enrolled in Part A and willing to consent to Part B of this protocol
* Pregnant with current chronic neuropathic pain
* Subjects failed treatment with amitriptyline or nortriptyline as defined by one of the following:

* no clinical improvement following a 4-week trial of amitriptyline or nortriptyline (i.e., CGI-I score ≥4)
* an inability to tolerate the medication (i.e., side effects)
* Subjects must pass the TMS Safety Checklist Adult Safety Screen (TASS).
* Subjects should be off medication, which can lower seizure thresholds (e.g., amitriptyline and nortriptyline) for at least two weeks prior to study entry.
* Subjects with neuropathic pain including those with diagnosis of spinal cord injury, fibromyalgia, compression neuropathies (including diabetic peripheral neuropathy), post stroke pain, and multiple sclerosis
* Subjects with a baseline VAS score greater than 30

Exclusion Criteria

* Active or history of substance use disorder within the past year
* Non-English speaking

Part B


* Current or past history of a seizure disorder (e.g., epilepsy)
* Current history of preeclampsia
* Current or history of brain lesions (e.g., aneurysm)
* History of major head trauma (e.g., stroke; previous cranial neurosurgery)
* Ferromagnetic metal in the head, neck, or chest (e.g., plates or pins, bullets, shrapnel)
* Microprocessor implants in the head (e.g., cochlear implants) or life-sustaining microprocessor implants anywhere in the body (e.g., prosthetic cardiac valves)
* Cardiac pacemaker
* Active or inactive implants (e.g., deep brain stimulators, vagus nerve stimulators)
* Active treatment with medications that lower seizure threshold (e.g., bupropion, amitriptyline, nortriptyline, or other TCA)
* Increased intracranial pressure (which lowers seizure threshold)
* Implanted medication pumps
* Intracardiac lines
* Significant heart disease defined as heart disease that causes moderate to severe symptoms and/or is characterized by moderate to severe pathology, including a recent history of myocardial infarction and heart failure with an ejection fraction of less than 30% or with a New York Heart Association Functional Classification of Class III or IV.
* Bipolar disorder (to reduce the risk of mania)
* History of suicide attempt(s)
* Family history of epilepsy
* Heavy alcohol consumption within the past 48 hours
* Permanent makeup or tattoos with metallic dyes
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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University of Arkansas

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Shona L Ray-Grififth, MD

Role: PRINCIPAL_INVESTIGATOR

University of Arkansas

Locations

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University of Arkansas For Medical Sciences

Little Rock, Arkansas, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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204737

Identifier Type: -

Identifier Source: org_study_id

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