Optimization of NIBS for Diabetic Neuropathy Neuropathic Pain

Not Applicable

Recruiting

• Conditions: Chronic Pain; Diabetic Neuropathies
• Interventions: Device: Sham

• Registration Number: NCT03625752
• Lead Sponsor: Case Western Reserve University

Brief Summary

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.

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 Timeline

• Study First Submitted: 2018-07-27
• Study First Submitted QC: 2018-08-09
• Study First Posted: 2018-08-10
• Study Start: 2019-06-06
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-16
• Last Update Posted: 2025-02-18
• Primary Completion: 2025-05-01
• Study Completion: 2025-05-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sham	Sham	Subjects in the sham group will undergo 20 minutes of sham transcranial direct current stimulation (tDCS) and sham transcranial ultrasound (TUS).

Primary Outcome Measures

Name	Time	Method
Changes in pain as measured by the Visual Analog Scale (VAS)	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.

Secondary Outcome Measures

Name	Time	Method
Changes in the Verbal Rating Scale (VRS) for Pain	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.
Electroencephalography	Measured for approximately 3 months	Investigators will measure electroencephalogram (EEG) electrical activity (EEG amplitude and EEG frequency) as function of time.
Patient Health Questionnaire (PHQ-9)	Measured for approximately 3 months	This questionnaire screens for depression with a score of 0 (best) to 27 (worst)
Multidimensional Pain Inventory (MPI)	Measured for approximately 3 months	This pain scale measures aspects of pain from 0 (best) to 6 (worst)
Changes in Conditional Pain Modulation	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.
Montreal Cognitive Assessment	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.
N-back tests	Measured for approximately 3 months	Assesses registration and immediate recall on a scale of the number of items correctly responded to
Functional reach test	Measured for approximately 3 months	The investigators will measure changes in subjects ability to complete the functional reach test across the duration of study.
American Pain Foundation Pain and Medication Diary	Measured for approximately 3 months	The pain sub-scale measures pain intensity from 0 (best) to 10 (worst)
Brief Pain Inventory-DPN	Measured for approximately 3 months	This pain scale measures aspects of pain from 0 (no pain) to 10 (worst)
Adverse events	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.
Changes in Visual Analog Scalefor Mood (VAMS)	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).
Study 36-Item Short Form (SF-36)	Measured for approximately 3 months	This is a health survey using a scale from 0 (worst) to 100 (best)
4-choice reaction time	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.
Walking test	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

Trial Locations

Locations (2)

University Hospitals Cleveland Medical Center/ Dahms Clinical Research Unit; 🇺🇸 Cleveland, Ohio, United States

Ciro Ramos Estebanez; 🇺🇸 Chicago, Illinois, United States