Noninvasive Brain Stimulation for Diabetic Neuropathic Pain

Chronic Pain Clinical Trial

Official title:

Optimization of ESStim for the Diabetic Neuropathic Pain Treatment Phase II Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05469074
• Other study ID #: STUDY20201584
• Status: Recruiting
• Phase: Phase 2
• Start date: February 25, 2022
• Est. completion date: August 1, 2024

Study information

• Verified date: July 2022
• Source: Case Western Reserve University
• Contact: Megan O'Neill O'Neill Miller
• Phone: 216-844-4720
• Email: megan.miller3[@]uhhospitals.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: August 1, 2024
• Est. primary completion date: August 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Providing informed consent to participate in the study.

2. 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.

3. 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.

4. Must have the ability to feel pain as self-reported.

Exclusion Criteria:

1. Subject is pregnant.

2. Contraindications to Electrosonic Stimulation (ESStim): metal in the head, or implanted brain medical devices.

3. History of alcohol or drug abuse within the past 6 months as self-reported.

4. Use of carbamazepine within the past 6 months as self-reported.

5. Suffering from major depression (with a PHQ-9 score of =10).

6. 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))

7. History of unexplained fainting spells as self-reported.

8. History of head injury resulting in more than a momentary loss of consciousness as self-reported.

9. History of neurosurgical procedures as self-reported.

10. 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.

Related Conditions & MeSH terms

• Chronic Pain
• Diabetic Neuropathies
• Neuralgia

Intervention

Device:
• Active tDCS + Active TUS
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.
• Device: Sham
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.

Locations

Country	Name	City	State
United States	University Hospitals Cleveland Medical Center/ Dahms Clinical Research Unit	Cleveland	Ohio
United States	University of Illinois Health/ University of Illinois at Chicago	Hinsdale	Illinois
United States	University of Illinois Health/ University Of Illinois at Chicago	Hinsdale	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Case Western Reserve University	Highland Instruments, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	3 months
Secondary	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.	3 months
Secondary	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.	3 months
Secondary	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).	3 months
Secondary	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.	3 months
Secondary	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.	3 months
Secondary	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.	3 months
Secondary	Electroencephalography	Investigators will measure electroencephalogram electrical activity (amplitude) as function of time.	3 months
Secondary	Electroencephalography	Investigators will measure electroencephalogram electrical activity (frequency) as function of time.	3 months
Secondary	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	3 months
Secondary	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	3 months
Secondary	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	3 months
Secondary	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	3 months
Secondary	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	3 months
Secondary	Functional reach test	The investigators will measure changes in subjects ability to complete the functional reach test across the duration of study.	3 months
Secondary	Study 36-Item Short Form	This is a health survey using a scale from 0 (worst) to 100 (best)	3 months
Secondary	Patient Health Questionnaire	This questionnaire screens for depression with a score of 0 (best) to 27 (worst)	3 months
Secondary	American Pain Foundation Pain and Medication Diary	The pain sub-scale measures pain intensity from 0 (best) to 10 (worst)	3 months
Secondary	Multidimensional Pain Inventory	This pain scale measures aspects of pain from 0 (best) to 6 (worst)	3 months
Secondary	Brief Pain Inventory	This pain scale measures aspects of pain from 0 (no pain) to 10 (worst)	3 months
Secondary	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.	3 months
Secondary	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).	3 months
Secondary	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).	3 months
Secondary	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).	3 months