Diabetic NeuropathiesNCT03625752
Optimization of NIBS for Diabetic Neuropathy Neuropathic Pain
A study testing Active Comparator: Active tDCS + Active TUS in people with Diabetic Neuropathies and Chronic Pain, run by Case Western Reserve University at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Diabetic Neuropathies, Chronic Pain
- What is being tested?
- Active Comparator: Active tDCS + Active TUS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 2 sitesUnited States
- Study dates
- 6 Jun 2019to 7 May 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able to provide informed consent to participate in the study.
- Subjects between 40 to 80 years old.
- 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).
- 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.
- Must have the ability to feel pain as self-reported.
Who cannot join
- Subject is pregnant.
- Contraindications to tDCS in conjunction with TUS, i.e. metallic implant in the brain 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 severe depression (with a PHQ 9 score of ≥ 10).
- History of neurological disorders as self-reported.
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- History of unexplained fainting spells as self-reported.
- History of severe head injury resulting in more than a momentary loss of consciousness as self-reported.
- History of neurosurgery 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).
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Ciro Ramos Estebanez
Chicago, Illinois, 60612
University Hospitals Cleveland Medical Center/ Dahms Clinical Research Unit
Cleveland, Ohio, 44106-1716
About this study
Official title: 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.
Read the 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).
- Conditions
- Diabetic Neuropathies, Chronic Pain
- Being tested
- Active Comparator: Active tDCS + Active TUS, Sham
- Medical subject headings
- Diabetic Neuropathies, Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active Comparator: Active tDCS + Active TUSDevice
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.
ShamDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Active Comparator: Active tDCS + Active TUS | Active comparator | Subjects in the experimental group will undergo 20 minutes of active transcranial direct current stimulation (tDCS) and active transcranial ultrasound (TUS). Receives: Device: Active Comparator: Active tDCS + Active TUS |
| Sham | Sham comparator | Subjects in the sham group will undergo 20 minutes of sham transcranial direct current stimulation (tDCS) and sham transcranial ultrasound (TUS). Receives: Device: Sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in pain as measured by the Visual Analog Scale (VAS)
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: Measured for approximately 3 months
Secondary outcomes (15)
Changes in the Verbal Rating Scale (VRS) for Pain
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: Measured for approximately 3 months
Changes in Conditional Pain Modulation
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: Measured for approximately 3 months
Changes in Visual Analog Scalefor Mood (VAMS)
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: Measured for approximately 3 months
Montreal Cognitive Assessment
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: Measured for approximately 3 months
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.
Measured: Measured for approximately 3 months
N-back tests
Assesses registration and immediate recall on a scale of the number of items correctly responded to
Measured: Measured for approximately 3 months
Electroencephalography
Investigators will measure electroencephalogram (EEG) electrical activity (EEG amplitude and EEG frequency) as function of time.
Measured: Measured for approximately 3 months
Walking test
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: Measured for approximately 3 months
Functional reach test
The investigators will measure changes in subjects ability to complete the functional reach test across the duration of study.
Measured: Measured for approximately 3 months
Study 36-Item Short Form (SF-36)
This is a health survey using a scale from 0 (worst) to 100 (best)
Measured: Measured for approximately 3 months
Patient Health Questionnaire (PHQ-9)
This questionnaire screens for depression with a score of 0 (best) to 27 (worst)
Measured: Measured for approximately 3 months
American Pain Foundation Pain and Medication Diary
The pain sub-scale measures pain intensity from 0 (best) to 10 (worst)
Measured: Measured for approximately 3 months
Multidimensional Pain Inventory (MPI)
This pain scale measures aspects of pain from 0 (best) to 6 (worst)
Measured: Measured for approximately 3 months
Brief Pain Inventory-DPN
This pain scale measures aspects of pain from 0 (no pain) to 10 (worst)
Measured: Measured for approximately 3 months
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.
Measured: Measured for approximately 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2018
- Study start6 Jun 2019
- Primary completion1 May 2027 (estimated)
- Study completion7 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetic NeuropathiesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- single-center, double-blinded, placebo controlled, randomized study.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Case Western Reserve University
- Sponsor type
- University, hospital or other
- Collaborators
- Highland Instruments, Inc.
- Responsible party
- Principal investigator, Ciro Ramos Estebanez, MD., Ph.D., Case Western Reserve University
- Investigators
- Salim Hayek, MD PhD, Principal investigator, University Hospitals Cleveland Medical Center/ Case Western Reserve University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03625752
- Sponsor's protocol ID
- STUDY20180314-2/20201584
- Status last verified
- Jun 2026
- First submitted
- 27 Jul 2018
- Last updated
- 29 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimization of Non-Invasive Brain Stimulation for Diabetic Neuropathy
- ClinicalTrials.gov ID
- NCT03625752
- Acronym / sponsor ID
- STUDY20180314-2/20201584
- Conditions
- Diabetic Neuropathies, Chronic Pain
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Case Western Reserve UniversityUniversity, hospital or other
- Collaborators
- Highland Instruments, Inc.
- Study start
- 6 Jun 2019 (actual)
- Primary completion
- 1 May 2027 (estimated)
- Study completion
- 7 May 2027 (estimated)
- First posted
- 10 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- single-center, double-blinded, placebo controlled, randomized study.
| Arm | Type | Receives |
|---|---|---|
| Active Comparator: Active tDCS + Active TUS | Active comparator | Device: Active Comparator: Active tDCS + Active TUSSubjects in the experimental group will undergo 20 minutes of active transcranial direct current stimulation (tDCS) and active transcranial ultrasound (TUS). |
| Sham | Sham comparator | Device: ShamSubjects in the sham group will undergo 20 minutes of sham transcranial direct current stimulation (tDCS) and sham transcranial ultrasound (TUS). |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Able to provide informed consent to participate in the study.
- Subjects between 40 to 80 years old.
- 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).
- 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.
- Must have the ability to feel pain as self-reported.
Key exclusion criteria (10 listed)
- Subject is pregnant.
- Contraindications to tDCS in conjunction with TUS, i.e. metallic implant in the brain 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 severe depression (with a PHQ 9 score of ≥ 10).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active Comparator: Active tDCS + Active TUSDevice: 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. | Device | Active Comparator: Active tDCS + Active TUS |
| ShamDevice: 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. | Device | Sham |
Primary outcome
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.
15 secondary outcomes
Changes in the Verbal Rating Scale (VRS) for Pain
Time frame: Measured for approximately 3 months
Changes in Conditional Pain Modulation
Time frame: Measured for approximately 3 months
Changes in Visual Analog Scalefor Mood (VAMS)
Time frame: Measured for approximately 3 months
Montreal Cognitive Assessment
Time frame: Measured for approximately 3 months
4-choice reaction time
Time frame: Measured for approximately 3 months
N-back tests
Time frame: Measured for approximately 3 months
Electroencephalography
Time frame: Measured for approximately 3 months
Walking test
Time frame: Measured for approximately 3 months
Functional reach test
Time frame: Measured for approximately 3 months
Study 36-Item Short Form (SF-36)
Time frame: Measured for approximately 3 months
Patient Health Questionnaire (PHQ-9)
Time frame: Measured for approximately 3 months
American Pain Foundation Pain and Medication Diary
Time frame: Measured for approximately 3 months
Multidimensional Pain Inventory (MPI)
Time frame: Measured for approximately 3 months
Brief Pain Inventory-DPN
Time frame: Measured for approximately 3 months
Adverse events
Time frame: Measured for approximately 3 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Salim Hayek, MD PhD principal investigator
University Hospitals Cleveland Medical Center/ Case Western Reserve University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active Comparator: Active tDCS + Active TUS in people with Diabetic Neuropathies and Chronic Pain, run by Case Western Reserve University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 29 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in pain as measured by the Visual Analog Scale (VAS) (time frame: Measured for approximately 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2026.