Optimization of NIBS for Diabetic Neuropathy Neuropathic Pain

September 5, 2023 updated by: Ciro Ramos Estebanez, MD., Ph.D., Case Western Reserve University

Optimization of Non-Invasive Brain Stimulation for Diabetic Neuropathy

The purpose of this study is to assess the effects of Transcranial Direct Current Stimulation (tDCS) in combination with Transcranial ultrasound (TUS) for the treatment of pain and functional limitations in subjects with Diabetic Neuropathic Pain.

Study Overview

Detailed Description

Active stimulation will be compared with compared to SHAM stimulation in DNP patients.

20 DNP patients, 10 per group, receive stimulation or sham for 5 consecutive days, 20 min/day, followed by 2, 4, and 6 weeks post-therapy. 9 visits plus screening/baseline (total 10 visits).

Subsequently, 40 DNP patients will be enrolled, 20 per group, giving 5 consecutive days, 20 min/day, followed by 2 weeks of bi-weekly stimulation or sham for 20 min/day (total stimulations n=9) and follow-ups at 2, 4, 6, & 8 weeks post-stim): 13 visits plus screening/ baseline (total 14 visits).

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • Illinois
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • Ciro Ramos Estebanez
        • Contact:
        • Principal Investigator:
          • Ciro Ramos Estebanez, MD., Ph.D.
    • Ohio
      • Cleveland, Ohio, United States, 44106-1716
        • Recruiting
        • University Hospitals Cleveland Medical Center/ Dahms Clinical Research Unit
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Able to provide informed consent to participate in the study.
  2. Subjects between 40 to 80 years old.
  3. Having diabetic neuropathic pain, involving at least 1 foot, with 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).
  4. Having 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.
  5. Must have the ability to feel pain as self-reported.

Exclusion Criteria:

  1. Subject is pregnant.
  2. Contraindications to tDCS in conjunction with TUS, i.e. metallic implant in the brain 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 severe depression (with a PHQ 9 score of ≥ 10).
  6. History of neurological disorders as self-reported.
  7. History of unexplained fainting spells as self-reported.
  8. History of severe head injury resulting in more than a momentary loss of consciousness as self-reported.
  9. History of neurosurgery 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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Active Comparator: Active tDCS + Active TUS
Subjects in the experimental group will undergo 20 minutes of active transcranial direct current stimulation (tDCS) and active transcranial ultrasound (TUS).
Device: transcranial Direct Current Stimulation (tDCS) Subjects will receive 20 minutes of either active or sham tDCS at intensity of 2mA. The anodal electrode will be placed over the primary motor cortex contralateral to the most painful side, and the cathodal electrode will be placed over the contralateral supraorbital area. 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 either active or sham TUS. During active stimulation the ultrasound will be active for the full 20 minutes- however, during sham stimulation the ultrasound will not be active for the full 20 minutes.
Sham Comparator: Sham
Subjects in the sham group will undergo 20 minutes of sham transcranial direct current stimulation (tDCS) and sham transcranial ultrasound (TUS).
Device: SHAM Comparator Device: transcranial Direct Current Stimulation (tDCS) Subjects will receive 20 minutes of either active or sham tDCS at intensity of 2mA. The anodal electrode will be placed over the primary motor cortex contralateral to the most painful side, and the cathodal electrode will be placed over the contralateral supraorbital area. 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 either active or sham TUS. During active stimulation the ultrasound will be active for the full 20 minutes- however, during sham stimulation the ultrasound will not be active for the full 20 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in pain as measured by the Visual Analog Scale (VAS)
Time Frame: Measured for approximately 3 months
The 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 (tDCS) in conjunction with transcranial ultrasound (TUS) (applied in a diagnostic mode) is effective in reducing pain of subjects with diabetic neuropathic pain.
Measured for approximately 3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in the Verbal Rating Scale (VRS) for Pain
Time Frame: Measured for approximately 3 months
The VRS 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 (tDCS) in conjunction. with transcranial ultrasound (TUS) (applied in a diagnostic mode) is effective in reducing pain of subjects with diabetic neuropathic pain.
Measured for approximately 3 months
Changes in Conditional Pain Modulation
Time Frame: Measured for approximately 3 months
Changes in Conditional Pain Modulation (CPM) will be measured in order to determine whether anodal transcranial direct current stimulation (tDCS) in conjunction with transcranial ultrasound (TUS) (applied in a diagnostic mode) is effective in increasing the pain pressure threshold in subjects with diabetic neuropathic pain.
Measured for approximately 3 months
Changes in Visual Analog Scalefor Mood (VAMS)
Time Frame: Measured for approximately 3 months

The VAS for Mood will investigate Anxiety, Depression, Stress, and Sleepiness. The Subscales are as follows:

The anxiety scale will assess a patient's anxiety on a scale from 0 (not anxious) to 10 (very anxious).

The depression scale will assess a patient's depression on a scale from 0 (not depressed) to 10 (very depressed).

The stress scale will assess a patient's stress on a scale from 0 (not stressed) to 10 (very stressed).

The sleepiness scale will assess a patient's depression on a scale from 0 (not sleepy) to 10 (very sleepy).

Measured for approximately 3 months
Montreal Cognitive Assessment
Time Frame: Measured for approximately 3 months
The investigators will monitor the safety of tDCS and TUS in subjects by measuring any changes in cognition. Scores range from lowest being 0 to highest being 30.
Measured for approximately 3 months
4-choice reaction time
Time Frame: Measured for approximately 3 months
This is an attentional task that measures the time for a subject response to stimuli (in seconds) with shorter times being better.
Measured for approximately 3 months
N-back tests
Time Frame: Measured for approximately 3 months
Assesses registration and immediate recall on a scale of the number of items correctly responded to
Measured for approximately 3 months
Electroencephalography
Time Frame: Measured for approximately 3 months
Investigators will measure electroencephalogram (EEG) electrical activity (EEG amplitude and EEG frequency) as function of time.
Measured for approximately 3 months
Walking test
Time Frame: Measured for approximately 3 months
The investigators will measure if there are changes in the walking speed, gait asymmetry, stride length, and walking smoothness of the subject from the beginning of the study to the end
Measured for approximately 3 months
Functional reach test
Time Frame: Measured for approximately 3 months
The investigators will measure changes in subjects ability to complete the functional reach test across the duration of study.
Measured for approximately 3 months
Study 36-Item Short Form (SF-36)
Time Frame: Measured for approximately 3 months
This is a health survey using a scale from 0 (worst) to 100 (best)
Measured for approximately 3 months
Patient Health Questionnaire (PHQ-9)
Time Frame: Measured for approximately 3 months
This questionnaire screens for depression with a score of 0 (best) to 27 (worst)
Measured for approximately 3 months
American Pain Foundation Pain and Medication Diary
Time Frame: Measured for approximately 3 months
The pain sub-scale measures pain intensity from 0 (best) to 10 (worst)
Measured for approximately 3 months
Multidimensional Pain Inventory (MPI)
Time Frame: Measured for approximately 3 months
This pain scale measures aspects of pain from 0 (best) to 6 (worst)
Measured for approximately 3 months
Brief Pain Inventory-DPN
Time Frame: Measured for approximately 3 months
This pain scale measures aspects of pain from 0 (no pain) to 10 (worst)
Measured for approximately 3 months
Adverse events
Time Frame: Measured for approximately 3 months
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.
Measured for approximately 3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Salim Hayek, MD PhD, University Hospitals Cleveland Medical Center/ Case Western Reserve University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 6, 2019

Primary Completion (Estimated)

June 7, 2024

Study Completion (Estimated)

May 7, 2025

Study Registration Dates

First Submitted

July 27, 2018

First Submitted That Met QC Criteria

August 9, 2018

First Posted (Actual)

August 10, 2018

Study Record Updates

Last Update Posted (Actual)

September 7, 2023

Last Update Submitted That Met QC Criteria

September 5, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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