Theta Burst Brain Stimulation in Diabetic Neuropathy Patients With Neuropathic Pain: Investigating Neural Mechanisms
Primary Purpose
Diabetic Neuropathy, Painful
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Prolonged continuous theta burst stimulation (pcTBS)
Sponsored by
About this trial
This is an interventional basic science trial for Diabetic Neuropathy, Painful focused on measuring transcranial magnetic stimulation, non-invasive brain stimulation
Eligibility Criteria
Inclusion Criteria:
- Patients with type II Diabetes Mellitus.
- Age 18-75 years.
- Diagnosed by a Physician with diabetic neuropathy/ distal symmetric polyneuropathy/ diabetic polyneuropathy.
- Patients under physician care at Virginia Commonwealth University Health Systems in the Neurology Clinic/ Neurology Department and the Endocrinology Clinic
- Neuropathic pain for at least 3 months.
- Neuropathic pain signs and symptoms identified using Pain DETECT questionnaire.
- Current pain score ≥3 or higher (0='no pain' and 10='worst possible pain').
- Pain Medication dosage stable for at least 4 weeks
Exclusion Criteria:
- Non-neuropathic chronic pain
- Another concurrent cause of neuropathic pain
- Any history of epilepsy, drug-resistant migraine, and/or any presence of ferromagnetic implant, cardiac pacemakers, implanted insulin pumps, neurostimulators, cochlear implants and surgical clips or medical pumps.
- Limited English proficiency
- Pregnant patients
Sites / Locations
- Virginia Commonwealth University
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Primary motor cortex (M1)
Dorsolateral prefrontal cortex (DLPFC)
Arm Description
Stimulation of the M1
Stimulation of the DLPFC
Outcomes
Primary Outcome Measures
Change in Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) score
The QOL-DN is questionnaire is an instrument to assess quality of life in patients with diabetic polyneuropathy. It is comprised of 35 items and yields a Total QOL score.
Change in bodily and emotional perception of pain (BEEP) score
The BEEP questionnaire is a self-report questionnaire measuring the impact of chronic pain on daily life. It has 23 items on a 0-5 Likert scale that assesses three pain dimensions, namely the emotional reaction to pain, the limitations to daily life caused by pain and the interference caused by pain in personal and social functioning. Responses are summed to yield a single BEEP score.
Secondary Outcome Measures
Change in pain threshold - conditioned pain modulation (CPM)
To measure CPM, brief amounts of slight pressure using a handheld pressure device will be applied to a location either on the forearm or leg where the patient reports a current absence of pain. An average index percent ratio will be calculated from the pressure device in kilopascals at which participants report the pressure was first perceived as painful during a baseline assessment and during an assessment when the participant's contralateral hand was placed in cold water. Change will be measured by subtracting CPM scores before and after the active procedure.
Change in pain threshold - Temporal Summation of Pain (TSP)
To measure TSP, the same pressure using a handheld pressure device that was perceived as first painful will be applied to a location either on the forearm or leg where the patient reports a current absence of pain. This pressure will be applied repeatedly applied 10 times and participants will be asked to report their pain on a 0-10 scale where 0 is no pain and 10 is worst pain imaginable. Change will be measured by subtracting TSP scores before and after the active procedure.
Change in pain threshold - Offset Analgesia (OA)
A Velcro strap tied to participants forearm connected to a device that transmits heat will be used to measure OA. Three different temperatures of mild heat will be applied. Participants will use a visual analog scale (VAS, no heat 0- extreme heat 10) to rate the intensity of the heat stimulus at each temperature. Minimal VAS ratings at the highest temperature will be subtracted from maximal VAS ratings at the lowest temperature to yield OA value. Change will be measured by subtracting OA values before and after the active procedure.
Change in cortical inhibition (CI)
The amplitude the motor evoked potentials (MEPS) from two simultaneous pulses will be used to determine level of cortical inhibition.
Change in corticospinal excitability (CE)
The amplitude the motor evoked potentials (MEPS) from a single pulse will be used to determine level of corticomotor excitability
Full Information
NCT ID
NCT04988321
First Posted
July 23, 2021
Last Updated
June 21, 2022
Sponsor
Virginia Commonwealth University
1. Study Identification
Unique Protocol Identification Number
NCT04988321
Brief Title
Theta Burst Brain Stimulation in Diabetic Neuropathy Patients With Neuropathic Pain: Investigating Neural Mechanisms
Official Title
Theta Burst Brain Stimulation in Diabetic Neuropathy Patients With Neuropathic Pain: Investigating Neural Mechanisms
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
September 3, 2021 (Actual)
Primary Completion Date
June 16, 2022 (Actual)
Study Completion Date
June 16, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Virginia Commonwealth University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
5. Study Description
Brief Summary
The purpose of the study is to determine the effects of a newer form of non-invasive brain stimulation (called transcranial magnetic stimulation or TMS) as a treatment in patients with painful diabetic neuropathy to examine its effects on their understanding of their pain experience.
Detailed Description
The proposed brain stimulation technique in this study is an investigational procedure that has not been approved by the U.S. FDA for treating pain linked to diabetic neuropathy, but it has been approved to treat depression. The study will use surveys to monitor how participant's body changes as their understanding of their pain experience changes. Participants will be randomized (like the flip of a coin) to receive brain stimulation at one of two brain regions which are involved in the processing and understanding of the pain experience.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Neuropathy, Painful
Keywords
transcranial magnetic stimulation, non-invasive brain stimulation
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
49 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Primary motor cortex (M1)
Arm Type
Active Comparator
Arm Description
Stimulation of the M1
Arm Title
Dorsolateral prefrontal cortex (DLPFC)
Arm Type
Active Comparator
Arm Description
Stimulation of the DLPFC
Intervention Type
Procedure
Intervention Name(s)
Prolonged continuous theta burst stimulation (pcTBS)
Intervention Description
Non-invasive brain stimulation (transcranial magnetic stimulation or TMS) which consists of a stimulating coil being held over the head. When this coil delivers a painless magnetic pulse, it feels like a quick, light tap on the head. Two different coils will be used to perform TMS. One coil will be used to determine stimulation parameters for the pcTBS protocol. The second coil will be used to implement pcTBS, which is a repetitive non-invasive brain stimulation protocol which feels like many quick, light taps on the head. Participants will receive two procedures during one session, one with active stimulation and one with inactive stimulation.
Primary Outcome Measure Information:
Title
Change in Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) score
Description
The QOL-DN is questionnaire is an instrument to assess quality of life in patients with diabetic polyneuropathy. It is comprised of 35 items and yields a Total QOL score.
Time Frame
Baseline to the end of the procedure, about 2.25 hours
Title
Change in bodily and emotional perception of pain (BEEP) score
Description
The BEEP questionnaire is a self-report questionnaire measuring the impact of chronic pain on daily life. It has 23 items on a 0-5 Likert scale that assesses three pain dimensions, namely the emotional reaction to pain, the limitations to daily life caused by pain and the interference caused by pain in personal and social functioning. Responses are summed to yield a single BEEP score.
Time Frame
Baseline to the end of the procedure, about 2.25 hours
Secondary Outcome Measure Information:
Title
Change in pain threshold - conditioned pain modulation (CPM)
Description
To measure CPM, brief amounts of slight pressure using a handheld pressure device will be applied to a location either on the forearm or leg where the patient reports a current absence of pain. An average index percent ratio will be calculated from the pressure device in kilopascals at which participants report the pressure was first perceived as painful during a baseline assessment and during an assessment when the participant's contralateral hand was placed in cold water. Change will be measured by subtracting CPM scores before and after the active procedure.
Time Frame
Baseline to the end of the procedure, about 2.25 hours
Title
Change in pain threshold - Temporal Summation of Pain (TSP)
Description
To measure TSP, the same pressure using a handheld pressure device that was perceived as first painful will be applied to a location either on the forearm or leg where the patient reports a current absence of pain. This pressure will be applied repeatedly applied 10 times and participants will be asked to report their pain on a 0-10 scale where 0 is no pain and 10 is worst pain imaginable. Change will be measured by subtracting TSP scores before and after the active procedure.
Time Frame
Baseline to the end of the procedure, about 2.25 hours
Title
Change in pain threshold - Offset Analgesia (OA)
Description
A Velcro strap tied to participants forearm connected to a device that transmits heat will be used to measure OA. Three different temperatures of mild heat will be applied. Participants will use a visual analog scale (VAS, no heat 0- extreme heat 10) to rate the intensity of the heat stimulus at each temperature. Minimal VAS ratings at the highest temperature will be subtracted from maximal VAS ratings at the lowest temperature to yield OA value. Change will be measured by subtracting OA values before and after the active procedure.
Time Frame
Baseline to the end of the procedure, about 2.25 hours
Title
Change in cortical inhibition (CI)
Description
The amplitude the motor evoked potentials (MEPS) from two simultaneous pulses will be used to determine level of cortical inhibition.
Time Frame
Baseline to the end of the procedure, about 2.25 hours
Title
Change in corticospinal excitability (CE)
Description
The amplitude the motor evoked potentials (MEPS) from a single pulse will be used to determine level of corticomotor excitability
Time Frame
Baseline to the end of the procedure, about 2.25 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with type II Diabetes Mellitus.
Age 18-75 years.
Diagnosed by a Physician with diabetic neuropathy/ distal symmetric polyneuropathy/ diabetic polyneuropathy.
Patients under physician care at Virginia Commonwealth University Health Systems in the Neurology Clinic/ Neurology Department and the Endocrinology Clinic
Neuropathic pain for at least 3 months.
Neuropathic pain signs and symptoms identified using Pain DETECT questionnaire.
Current pain score ≥3 or higher (0='no pain' and 10='worst possible pain').
Pain Medication dosage stable for at least 4 weeks
Exclusion Criteria:
Non-neuropathic chronic pain
Another concurrent cause of neuropathic pain
Any history of epilepsy, drug-resistant migraine, and/or any presence of ferromagnetic implant, cardiac pacemakers, implanted insulin pumps, neurostimulators, cochlear implants and surgical clips or medical pumps.
Limited English proficiency
Pregnant patients
Facility Information:
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Theta Burst Brain Stimulation in Diabetic Neuropathy Patients With Neuropathic Pain: Investigating Neural Mechanisms
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