Back to resultsNoninvasive Brain Stimulation for Diabetic Neuropathic Pain
Primary Purpose
Diabetic Neuropathies, Chronic Pain
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Active tDCS + Active TUS
Device: Sham
Sponsored by
About this trial
This is an interventional treatment trial for Diabetic Neuropathies
Eligibility Criteria
Inclusion Criteria:
- Providing informed consent to participate in the study.
- Having diabetic neuropathic pain, involving at least 1 foot, as defined by International Association for the Study of Pain and meeting criteria detailed by the Toronto Diabetic Neuropathy Expert Group - existing pain for at least 6 months and having pain on at least half the days in the past 6 months with an average of at least a 4 on a 0-10 VAS scale.
- Pain resistant to common analgesics and medications for first line therapy of chronic pain such as Tylenol, Aspirin, Ibuprofen, Soma, Parafon Forte DCS, Zanaflex, Codeine, etc.
- Must have the ability to feel pain as self-reported.
Exclusion Criteria:
- Subject is pregnant.
- Contraindications to Electrosonic Stimulation (ESStim): metal in the head, or implanted brain medical devices.
- History of alcohol or drug abuse within the past 6 months as self-reported.
- Use of carbamazepine within the past 6 months as self-reported.
- Suffering from major depression (with a PHQ-9 score of ≥10).
- History of neurological disorders involving stroke, brain tumors, or epilepsy as self-reported (note patients will also be evaluated via EEG at baseline 1 week prior to stimulation and any patient showing abnormal EEG activity will be removed))
- History of unexplained fainting spells as self-reported.
- History of head injury resulting in more than a momentary loss of consciousness as self-reported.
- History of neurosurgical procedures as self-reported.
- Unstable pain (defined as pain intensities that vary by more than 4 points on 0-10 VAS scale over the 1-week period of trial run-in.
Sites / Locations
- University of Illinois Health/ University of Illinois at ChicagoRecruiting
- University of Illinois Health/ University Of Illinois at ChicagoRecruiting
- University Hospitals Cleveland Medical Center/ Dahms Clinical Research UnitRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Sham Comparator
Arm Label
Active tDCS + Active TUS
Sham
Arm Description
Subjects in the experimental group will undergo 20 minutes of active transcranial direct current stimulation (tDCS) and active transcranial ultrasound (TUS).
Subjects in the sham group will undergo 20 minutes of sham transcranial direct current stimulation (tDCS) and sham transcranial ultrasound (TUS).
Outcomes
Primary Outcome Measures
Changes in pain as measured by the Visual Analog Scale
The Visual Analog Scale will assess a patient's pain intensity on a scale from 0 (no pain) to 10 (worst pain imaginable). Changes in VAS for Pain will be measured to determine whether anodal transcranial direct current stimulation in conjunction with transcranial ultrasound (applied in a diagnostic mode) is effective in reducing pain of subjects with diabetic neuropathic pain.
Secondary Outcome Measures
Changes in the Verbal Rating Scale for Pain
The Verbal Rating Scale for Pain is a categorical scale of pain with categories: none, mild, moderate, severe pain intensity. Changes in VRS for Pain will be measured in order to determine whether anodal transcranial direct current stimulation in conjunction. with transcranial ultrasound (applied in a diagnostic mode) is effective in reducing pain of subjects with diabetic neuropathic pain.
Changes in Conditional Pain Modulation
Changes in Conditional Pain Modulation will be measured in order to determine whether anodal transcranial direct current stimulation in conjunction with transcranial ultrasound (applied in a diagnostic mode) is effective in increasing the pain pressure threshold (e.g., pounds per square inch) in subjects with diabetic neuropathic pain where a higher number is better and a lower number is worse.
Changes in Visual Analog Scale for Mood - Anxiety
The Visual Analog Scale for Mood will investigate Anxiety. The Subscales is as follows:
The anxiety scale will assess a patient's anxiety on a scale from 0 (not anxious) to 10 (very anxious).
Montreal Cognitive Assessment
The investigators will monitor the safety of transcranial direct current stimulation and transcranial ultrasound in subjects by measuring any changes in cognition. Scores range from lowest being 0 to highest being 30.
4-choice reaction time
This is an attentional task that measures the time for a subject response to stimuli (in seconds) with shorter times being better.
N-back tests
This instrument has been used in our past brain stimulation studies and will be used to assess working memory. This is a computer-assisted test.
Electroencephalography
Investigators will measure electroencephalogram electrical activity (amplitude) as function of time.
Electroencephalography
Investigators will measure electroencephalogram electrical activity (frequency) as function of time.
Walking test
The investigators will measure if there are changes in the walking speed of the subject from the beginning of the study to the end
Walking test
The investigators will measure if there are changes in the gait asymmetry of the subject from the beginning of the study to the end
Walking test
The investigators will measure if there are changes in the stride length, and walking smoothness of the subject from the beginning of the study to the end
Walking test
The investigators will measure if there are changes in the stride length of the subject from the beginning of the study to the end
Walking test
The investigators will measure if there are changes in the walking smoothness of the subject from the beginning of the study to the end
Functional reach test
The investigators will measure changes in subjects ability to complete the functional reach test across the duration of study.
Study 36-Item Short Form
This is a health survey using a scale from 0 (worst) to 100 (best)
Patient Health Questionnaire
This questionnaire screens for depression with a score of 0 (best) to 27 (worst)
American Pain Foundation Pain and Medication Diary
The pain sub-scale measures pain intensity from 0 (best) to 10 (worst)
Multidimensional Pain Inventory
This pain scale measures aspects of pain from 0 (best) to 6 (worst)
Brief Pain Inventory
This pain scale measures aspects of pain from 0 (no pain) to 10 (worst)
Adverse events
At each session after stimulation begins, subjects will complete a questionnaire to evaluate potential adverse effects of stimulation (headache, neck pain, mood alterations, and seizures) on a 5-point scale (0 being best and 5 worst). The scale will also be administered at the follow-up.
The Visual Analog Scale for Mood - Depression
The Visual Analog Scale for Mood will investigate Depression. The Subscales is as follows:
The depression scale will assess a patient's depression on a scale from 0 (not depressed) to 10 (very depressed).
The Visual Analog Scale for Mood - Stress
The Visual Analog Scale for Mood will investigate Stress. The Subscales is as follows:
The stress scale will assess a patient's stress on a scale from 0 (not stressed) to 10 (very stressed).
The Visual Analog Scale for Mood - Sleep
The Visual Analog Scale for Mood will investigate Sleepiness. The Subscales is as follows:
The sleepiness scale will assess a patient's depression on a scale from 0 (not sleepy) to 10 (very sleepy).
Full Information
NCT ID
NCT05469074
First Posted
March 14, 2022
Last Updated
July 20, 2022
Sponsor
Case Western Reserve University
Collaborators
Highland Instruments, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05469074
Brief Title
Noninvasive Brain Stimulation for Diabetic Neuropathic Pain
Official Title
Optimization of ESStim for the Diabetic Neuropathic Pain Treatment Phase II Study
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 25, 2022 (Actual)
Primary Completion Date
August 1, 2023 (Anticipated)
Study Completion Date
August 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Case Western Reserve University
Collaborators
Highland Instruments, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is an investigator-initiated study that is in the funding range for a grant from the NIH. This study is testing the possibility that non-invasive brain stimulation (ESSTim) would be superior to sham in the treatment of pain secondary to diabetic neuropathy.
Detailed Description
The investigators hypothesize that Active ESStim will have a significantly improved and lasting effect compared to SHAM ESStim assessed in 40 DNP patients, 20 per group, given now for 5 consecutive days, 20 min/day, followed by 2 weeks of bi-weekly stimulation given 20 min/day (total stimulations n=11) and follow-ups at 2, 4, 6, & 8 weeks post-stim): 13 visits plus screening/ baseline (total 14 visits).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Neuropathies, Chronic Pain
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
multicenter, double-blinded, placebo-controlled, randomized study.
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Active tDCS + Active TUS
Arm Type
Active Comparator
Arm Description
Subjects in the experimental group will undergo 20 minutes of active transcranial direct current stimulation (tDCS) and active transcranial ultrasound (TUS).
Arm Title
Sham
Arm Type
Sham Comparator
Arm Description
Subjects in the sham group will undergo 20 minutes of sham transcranial direct current stimulation (tDCS) and sham transcranial ultrasound (TUS).
Intervention Type
Device
Intervention Name(s)
Active tDCS + Active TUS
Intervention Description
Device: Active comparator device: Active transcranial Direct Current Stimulation (tDCS). Subjects will receive 20 minutes of active tDCS. During each Active stimulation session, stimulation will be applied for the full 20 minutes.
Device: Active comparator device: Active Transcranial Ultrasound (TUS). Subjects will receive 20 minutes of active Transcranial Ultrasound (TUS). During active stimulation the (TUS) will be active for the full 20 minutes.
Intervention Type
Device
Intervention Name(s)
Device: Sham
Intervention Description
Device: SHAM Comparator Device: transcranial Direct Current Stimulation (tDCS) Subjects will receive 20 minutes of sham tDCS. In the sham group, the tDCS device will not be active for the full 20 minutes.
Device: Transcranial Ultrasound (TUS) Subjects will receive 20 minutes of sham TUS. During sham stimulation the ultrasound will not be active for the full 20 minutes.
Primary Outcome Measure Information:
Title
Changes in pain as measured by the Visual Analog Scale
Description
The Visual Analog Scale will assess a patient's pain intensity on a scale from 0 (no pain) to 10 (worst pain imaginable). Changes in VAS for Pain will be measured to determine whether anodal transcranial direct current stimulation in conjunction with transcranial ultrasound (applied in a diagnostic mode) is effective in reducing pain of subjects with diabetic neuropathic pain.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Changes in the Verbal Rating Scale for Pain
Description
The Verbal Rating Scale for Pain is a categorical scale of pain with categories: none, mild, moderate, severe pain intensity. Changes in VRS for Pain will be measured in order to determine whether anodal transcranial direct current stimulation in conjunction. with transcranial ultrasound (applied in a diagnostic mode) is effective in reducing pain of subjects with diabetic neuropathic pain.
Time Frame
3 months
Title
Changes in Conditional Pain Modulation
Description
Changes in Conditional Pain Modulation will be measured in order to determine whether anodal transcranial direct current stimulation in conjunction with transcranial ultrasound (applied in a diagnostic mode) is effective in increasing the pain pressure threshold (e.g., pounds per square inch) in subjects with diabetic neuropathic pain where a higher number is better and a lower number is worse.
Time Frame
3 months
Title
Changes in Visual Analog Scale for Mood - Anxiety
Description
The Visual Analog Scale for Mood will investigate Anxiety. The Subscales is as follows:
The anxiety scale will assess a patient's anxiety on a scale from 0 (not anxious) to 10 (very anxious).
Time Frame
3 months
Title
Montreal Cognitive Assessment
Description
The investigators will monitor the safety of transcranial direct current stimulation and transcranial ultrasound in subjects by measuring any changes in cognition. Scores range from lowest being 0 to highest being 30.
Time Frame
3 months
Title
4-choice reaction time
Description
This is an attentional task that measures the time for a subject response to stimuli (in seconds) with shorter times being better.
Time Frame
3 months
Title
N-back tests
Description
This instrument has been used in our past brain stimulation studies and will be used to assess working memory. This is a computer-assisted test.
Time Frame
3 months
Title
Electroencephalography
Description
Investigators will measure electroencephalogram electrical activity (amplitude) as function of time.
Time Frame
3 months
Title
Electroencephalography
Description
Investigators will measure electroencephalogram electrical activity (frequency) as function of time.
Time Frame
3 months
Title
Walking test
Description
The investigators will measure if there are changes in the walking speed of the subject from the beginning of the study to the end
Time Frame
3 months
Title
Walking test
Description
The investigators will measure if there are changes in the gait asymmetry of the subject from the beginning of the study to the end
Time Frame
3 months
Title
Walking test
Description
The investigators will measure if there are changes in the stride length, and walking smoothness of the subject from the beginning of the study to the end
Time Frame
3 months
Title
Walking test
Description
The investigators will measure if there are changes in the stride length of the subject from the beginning of the study to the end
Time Frame
3 months
Title
Walking test
Description
The investigators will measure if there are changes in the walking smoothness of the subject from the beginning of the study to the end
Time Frame
3 months
Title
Functional reach test
Description
The investigators will measure changes in subjects ability to complete the functional reach test across the duration of study.
Time Frame
3 months
Title
Study 36-Item Short Form
Description
This is a health survey using a scale from 0 (worst) to 100 (best)
Time Frame
3 months
Title
Patient Health Questionnaire
Description
This questionnaire screens for depression with a score of 0 (best) to 27 (worst)
Time Frame
3 months
Title
American Pain Foundation Pain and Medication Diary
Description
The pain sub-scale measures pain intensity from 0 (best) to 10 (worst)
Time Frame
3 months
Title
Multidimensional Pain Inventory
Description
This pain scale measures aspects of pain from 0 (best) to 6 (worst)
Time Frame
3 months
Title
Brief Pain Inventory
Description
This pain scale measures aspects of pain from 0 (no pain) to 10 (worst)
Time Frame
3 months
Title
Adverse events
Description
At each session after stimulation begins, subjects will complete a questionnaire to evaluate potential adverse effects of stimulation (headache, neck pain, mood alterations, and seizures) on a 5-point scale (0 being best and 5 worst). The scale will also be administered at the follow-up.
Time Frame
3 months
Title
The Visual Analog Scale for Mood - Depression
Description
The Visual Analog Scale for Mood will investigate Depression. The Subscales is as follows:
The depression scale will assess a patient's depression on a scale from 0 (not depressed) to 10 (very depressed).
Time Frame
3 months
Title
The Visual Analog Scale for Mood - Stress
Description
The Visual Analog Scale for Mood will investigate Stress. The Subscales is as follows:
The stress scale will assess a patient's stress on a scale from 0 (not stressed) to 10 (very stressed).
Time Frame
3 months
Title
The Visual Analog Scale for Mood - Sleep
Description
The Visual Analog Scale for Mood will investigate Sleepiness. The Subscales is as follows:
The sleepiness scale will assess a patient's depression on a scale from 0 (not sleepy) to 10 (very sleepy).
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Providing informed consent to participate in the study.
Having diabetic neuropathic pain, involving at least 1 foot, as defined by International Association for the Study of Pain and meeting criteria detailed by the Toronto Diabetic Neuropathy Expert Group - existing pain for at least 6 months and having pain on at least half the days in the past 6 months with an average of at least a 4 on a 0-10 VAS scale.
Pain resistant to common analgesics and medications for first line therapy of chronic pain such as Tylenol, Aspirin, Ibuprofen, Soma, Parafon Forte DCS, Zanaflex, Codeine, etc.
Must have the ability to feel pain as self-reported.
Exclusion Criteria:
Subject is pregnant.
Contraindications to Electrosonic Stimulation (ESStim): metal in the head, or implanted brain medical devices.
History of alcohol or drug abuse within the past 6 months as self-reported.
Use of carbamazepine within the past 6 months as self-reported.
Suffering from major depression (with a PHQ-9 score of ≥10).
History of neurological disorders involving stroke, brain tumors, or epilepsy as self-reported (note patients will also be evaluated via EEG at baseline 1 week prior to stimulation and any patient showing abnormal EEG activity will be removed))
History of unexplained fainting spells as self-reported.
History of head injury resulting in more than a momentary loss of consciousness as self-reported.
History of neurosurgical procedures as self-reported.
Unstable pain (defined as pain intensities that vary by more than 4 points on 0-10 VAS scale over the 1-week period of trial run-in.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Megan O'Neill O'Neill Miller
Phone
216-844-4720
Email
megan.miller3@uhhospitals.org
First Name & Middle Initial & Last Name or Official Title & Degree
Terrah Morrison
Phone
216.844.2685
Email
Terrah.Morrison@UHhospitals.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Salim Hayek, MD PhD
Organizational Affiliation
University Hospitals Cleveland Medical Center/ Case Western Reserve University
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Illinois Health/ University of Illinois at Chicago
City
Hinsdale
State/Province
Illinois
ZIP/Postal Code
60521-4902
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elizabeth Villagrana
Phone
312-355-1528
Email
nevilla@uic.edu
First Name & Middle Initial & Last Name & Degree
Ciro Ramos Estebanez MD, PhD, MBA, FNCS
Email
cramoses@icloud.com
First Name & Middle Initial & Last Name & Degree
Ciro Ramos Estebanez, MD, PhD
Facility Name
University of Illinois Health/ University Of Illinois at Chicago
City
Hinsdale
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elizabeth Villagrana
Phone
312-413-0483
Email
nevilla@uic.edu
First Name & Middle Initial & Last Name & Degree
Ciro Ramos Estebanez MD, PhD, MBA, FNCS
Email
cramoses@icloud.com
First Name & Middle Initial & Last Name & Degree
Ciro RamosEstebanez, MD., Ph.D.
Facility Name
University Hospitals Cleveland Medical Center/ Dahms Clinical Research Unit
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106-1716
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jillian Russell, MSN, RN-BC
Phone
216-844-4901
Email
Jillian.Russell@uhhospitals.org
First Name & Middle Initial & Last Name & Degree
Salim Hayek, MD, PhD
Phone
216.844.2685
Email
Salim.Hayek@UHhospitals.org
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Noninvasive Brain Stimulation for Diabetic Neuropathic Pain
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