Noninvasive Brain Stimulation for Diabetic Neuropathy

Recruiting at 1 trial location

Overseen By Terrah Morrison

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Case Western Reserve University

Must not be taking: Carbamazepine

Disqualifiers: Pregnancy, Major depression, Neurological disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 15

Duration: 3 weeks

80 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment called non-invasive brain stimulation (ESSTim) for people with pain from diabetic neuropathy. The treatment uses mild electrical signals to change how the brain processes pain. Researchers believe this could be more effective. Non-invasive brain stimulation techniques have been explored for their potential to reduce chronic pain by altering brain activity.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that your pain should be resistant to common pain relievers like Tylenol, Aspirin, and Ibuprofen. It also states that you should not have used carbamazepine in the past 6 months.

What data supports the effectiveness of this treatment for diabetic neuropathy?

Research shows that transcranial direct current stimulation (tDCS) can help relieve pain in people with diabetic neuropathy, a common complication of diabetes. Studies have found that tDCS over specific brain areas can reduce pain, making it a promising non-drug treatment option for managing this condition. ^{1 2 3 4 5}

Is noninvasive brain stimulation, like tDCS, safe for humans?

Transcranial Direct Current Stimulation (tDCS) has been shown to be safe in human trials, with no reports of serious or irreversible side effects across over 33,200 sessions. The adverse effects are generally mild and temporary, making it a safe option for various conditions. ^{5 6 7 8 9}

How does the treatment of Active tDCS + Active TUS for diabetic neuropathy differ from other treatments?

This treatment is unique because it combines two non-invasive brain stimulation techniques, transcranial direct current stimulation (tDCS) and transcranial ultrasound (TUS), which aim to relieve pain by modulating brain activity without the need for medication. Unlike standard treatments that may involve drugs or invasive procedures, this approach uses electrical and sound waves to target specific brain areas involved in pain perception. ^{1 2 3 10 11}

Research Team

Salim Hayek, MD PhD

Principal Investigator

University Hospitals Cleveland Medical Center/ Case Western Reserve University

Eligibility Criteria

This trial is for adults with diabetic neuropathic pain in at least one foot, unresponsive to common painkillers, and have had this pain for over 6 months. Participants must not be pregnant, have metal in their head or implanted brain devices, a recent history of substance abuse, use of certain medications like carbamazepine, major depression, neurological disorders such as stroke or epilepsy, unexplained fainting spells, significant head injuries or neurosurgery.

Inclusion Criteria

I have had diabetic foot pain for at least 6 months, with pain most days.

My pain doesn't improve with regular painkillers like Tylenol or Ibuprofen.

I have had diabetic foot pain for at least 6 months, with pain most days and a pain level of at least 4.

Exclusion Criteria

I have not taken carbamazepine in the last 6 months.

I have major depression with a PHQ-9 score of 10 or higher.

I have had a head injury that caused me to lose consciousness.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive active or sham ESStim for 5 consecutive days, 20 min/day, followed by 2 weeks of bi-weekly stimulation, 20 min/day

3 weeks

11 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with follow-ups at 2, 4, 6, & 8 weeks post-stimulation

8 weeks

4 visits (in-person)

Long-term monitoring

Participants are assessed for changes in pain and other health measures over a 3-month period

3 months

Treatment Details

Interventions

• Active tDCS + Active TUS
• Sham

Trial Overview The study tests if non-invasive brain stimulation (ESSTim) can better manage chronic pain from diabetic neuropathy compared to a sham (fake treatment). It involves active transcranial direct current stimulation (tDCS) combined with ultrasound therapy (TUS), versus a placebo-like device without actual therapeutic effect.

Participant Groups

Group I: Active tDCS + Active TUS Active Control 1 Intervention

Subjects in the experimental group will undergo 20 minutes of active transcranial direct current stimulation (tDCS) and active transcranial ultrasound (TUS).

Group II: Sham Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

Case Western Reserve University

Lead Sponsor

Trials

314

Recruited

236,000+

Highland Instruments, Inc.

Industry Sponsor

Trials

11

Recruited

650+

Findings from Research

Transcranial direct current stimulation (tDCS) applied over the primary motor cortex (M1) significantly reduced pain in patients with painful diabetic polyneuropathy (PDPN), showing immediate effects and sustained relief for up to 4 weeks after treatment.

In a study of 60 patients, those receiving tDCS over M1 experienced greater pain reduction compared to those receiving sham or dorsolateral prefrontal cortex (DLPFC) stimulation, indicating that targeting M1 may be an effective approach for managing pain in PDPN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, sham controlled trial of transcranial direct current stimulation for painful diabetic polyneuropathy. Kim, YJ., Ku, J., Kim, HJ., et al.[2022]

Anodal transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) and left dorsolateral prefrontal cortex (F3) significantly reduced pain in patients with neuropathic pain due to type-2 diabetes, as shown in a study of 48 participants who received 12 sessions of treatment.

While the M1 stimulation group reported lower pain intensity immediately after treatment compared to the F3 group, both groups showed similar pain levels during follow-up, indicating that tDCS may be a beneficial but temporary add-on treatment for managing diabetic neuropathic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the separate and combined effects of anodal tDCS over the M1 and F3 regions on pain relief in patients with type-2 diabetes suffering from neuropathic pain. Alipour, A., Mohammadi, R.[2023]

In a case study involving a 24-year-old female patient undergoing 10 sessions of transcranial direct current stimulation (tDCS) for anorexia nervosa, hyperglycemia developed, leading to the onset of type I diabetes.

This case highlights a potential adverse effect of tDCS on glycemic control, suggesting that while tDCS is often studied for its benefits in other areas, its impact on blood sugar levels and diabetes risk requires further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Onset of Diabetes During Transcranial Direct Current Stimulation Treatment of Anorexia Nervosa - A Case Report. Mares, T., Ceresnakova, S., Albrecht, J., et al.[2020]

Transcranial direct current stimulation (tDCS) is a non-invasive technique that can influence neuronal activity and induce lasting synaptic changes, making it a promising treatment for neuropsychiatric disorders, particularly unipolar depression.

tDCS is advantageous due to its minimal side effects and potential for portability, which could allow for home use and enhance patient care in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive cortical stimulation: Transcranial direct current stimulation (tDCS). Sudbrack-Oliveira, P., Razza, LB., Brunoni, AR.[2022]

Transcranial Direct Current Stimulation (tDCS) has been shown to be safe, with no reports of Serious Adverse Effects or irreversible injuries across over 33,200 sessions involving more than 1,000 subjects, including vulnerable populations.

Safety assessments indicate that the current densities used in conventional tDCS (≤4 milliamperes) are significantly lower than those that could potentially cause brain injury, suggesting that tDCS protocols are well within safe limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Bikson, M., Grossman, P., Thomas, C., et al.[2022]

A systematic review of 64 studies involving 2262 participants found that transcranial direct current stimulation (tDCS) has a low dropout rate (6% for active and 7.2% for sham), indicating good acceptability among participants.

Despite the low dropout rates, many studies inadequately reported adverse events (AEs), highlighting a need for improved guidelines to standardize AE reporting in tDCS research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. Aparício, LVM., Guarienti, F., Razza, LB., et al.[2018]

Transcranial direct current stimulation (tDCS) has been found to be safe for use in humans, with no severe complications reported in studies involving both adults and children when applied at intensities of 4 mA or less for up to 60 minutes.

Animal studies indicate that the electrical current used in tDCS is significantly lower than the threshold that could cause permanent changes to brain tissue, suggesting a strong safety profile for this neurorehabilitation method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation in Neurorehabilitation. Ko, MH.[2023]

Transcranial direct current stimulation (tDCS) is a safe and well-tolerated technique, with no serious adverse effects reported in a study involving 131 healthy subjects across 277 sessions.

While sensory side effects like tingling and itching are common, they are generally mild; however, the higher occurrence and severity of these side effects during active stimulation compared to sham stimulation suggest that the current sham method may not be an effective control in some research contexts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in the experience of active and sham transcranial direct current stimulation. Kessler, SK., Turkeltaub, PE., Benson, JG., et al.[2021]

This study aims to evaluate the safety and effectiveness of personalized transcranial direct current stimulation (P-tDCS) in promoting awakening in 24 patients with disorders of consciousness (DOC) after acquired brain injury, using a tailored approach based on individual brain lesions.

The trial will compare the effects of P-tDCS combined with typical rehabilitation against sham tDCS over a 2-week period, assessing outcomes using the Korean version of the Coma Recovery Scale-Revised (K-CRS-R) to measure improvements in consciousness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and therapeutic effects of personalized transcranial direct current stimulation based on electrical field simulation for prolonged disorders of consciousness: study protocol for a multi-center, double-blind, randomized controlled trial. Yoon, MJ., Oh, HM., Kim, T., et al.[2023]

Deep repetitive transcranial magnetic stimulation (rTMS) using the H-coil significantly reduced pain levels in patients with diabetic neuropathy, as evidenced by a decrease in visual analogue scale (VAS) scores and RIII reflex area after treatment.

The study involved 25 patients, with 23 completing the trial, and showed that the pain relief effects lasted for about 3 weeks post-treatment, indicating that deep rTMS can effectively target deeper brain areas to modulate pain perception.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

H-coil repetitive transcranial magnetic stimulation for pain relief in patients with diabetic neuropathy. Onesti, E., Gabriele, M., Cambieri, C., et al.[2022]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Randomized, sham controlled trial of transcranial direct current stimulation for painful diabetic polyneuropathy. [2022]

2. Ireland pubmed.ncbi.nlm.nih.gov

Evaluation of the separate and combined effects of anodal tDCS over the M1 and F3 regions on pain relief in patients with type-2 diabetes suffering from neuropathic pain. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

The Onset of Diabetes During Transcranial Direct Current Stimulation Treatment of Anorexia Nervosa - A Case Report. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

MRI study of human brain exposed to weak direct current stimulation of the frontal cortex. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Non-invasive cortical stimulation: Transcranial direct current stimulation (tDCS). [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. [2018]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation in Neurorehabilitation. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Differences in the experience of active and sham transcranial direct current stimulation. [2021]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and therapeutic effects of personalized transcranial direct current stimulation based on electrical field simulation for prolonged disorders of consciousness: study protocol for a multi-center, double-blind, randomized controlled trial. [2023]

11. England pubmed.ncbi.nlm.nih.gov

H-coil repetitive transcranial magnetic stimulation for pain relief in patients with diabetic neuropathy. [2022]