CES for Generalized Anxiety Disorder

Overseen By Zachary Stewart

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Electromedical Products International, Inc.

Disqualifiers: Bipolar, Alcohol use disorder, Epilepsy, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 6 weeks

130 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

You don't have to stop taking your current medications, but you need to keep the dose stable for 2 weeks before the screening visit, or 4 weeks if you're on antidepressants. You can also participate if you're not taking any medications.

What data supports the effectiveness of the treatment At-Home Stimulation, Transcranial Direct Current Stimulation (tDCS), Cranial Electrotherapy Stimulation (CES), At-Home Brain Stimulation for Generalized Anxiety Disorder?

Research shows that both transcranial direct current stimulation (tDCS) and cranial electrotherapy stimulation (CES) can help reduce anxiety symptoms. Studies have found that tDCS, especially when combined with therapy, and CES are effective in treating anxiety and depression, with improvements seen in patients with generalized anxiety disorder. ^{1 2 3 4 5}

Is cranial electrotherapy stimulation (CES) safe for humans?

Cranial electrotherapy stimulation (CES) and similar techniques like transcranial direct current stimulation (tDCS) are generally considered safe for humans, with no serious adverse events reported in over 18,000 sessions. Mild side effects like headaches, fatigue, and skin sensations are possible, but serious issues are rare. ^{2 3 6 7 8}

How does At-Home Stimulation differ from other treatments for generalized anxiety disorder?

At-Home Stimulation, which includes techniques like transcranial direct current stimulation (tDCS) and cranial electrotherapy stimulation (CES), is unique because it is a non-invasive brain stimulation method that can be administered at home, offering convenience and potentially fewer side effects compared to traditional medication. It uses gentle electrical currents to influence brain activity, which is different from medications that alter brain chemistry. ^{2 3 4 5 9}

What is the purpose of this trial?

The purpose of this research study is to study cranial electrotherapy stimulation (CES) to determine its effects on symptoms of anxiety in people with generalized anxiety disorder (GAD) between the ages of 18 - 21 years of age.

Research Team

Samantha Meltzer-Brody, MD, MPH

Principal Investigator

University of North Carolina, Chapel Hill

Eligibility Criteria

This trial is for young adults aged 18-21 with Generalized Anxiety Disorder (GAD). Participants must be able to consent, follow the study's procedures, and use effective contraception if applicable. They should have mild-to-moderate anxiety symptoms and either maintain a stable dose of current psychiatric meds or not change their treatment during the study.

Inclusion Criteria

I am able to understand and sign the consent form.

I am willing to follow the study rules and be available for its duration without changing my treatment unless it's medically necessary.

I have been diagnosed with generalized anxiety disorder.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline

Baseline assessments including clinical assessments of anxiety symptoms and resting-state EEG collection

1 week

1 visit (in-person)

Treatment

Participants receive either active or sham CES daily for six weeks

6 weeks

At-home daily sessions

Follow-up 1

Clinical assessments of anxiety symptoms and resting-state EEG collection

1 week

1 visit (in-person)

Follow-up 2

Final clinical assessments of anxiety symptoms and other secondary outcomes

6 weeks

1 visit (in-person)

Treatment Details

Interventions

• At-Home Stimulation

Trial Overview The trial is testing cranial electrotherapy stimulation (CES) as an at-home treatment for reducing anxiety symptoms in individuals with GAD. It aims to understand how CES affects this age group when administered outside of a clinical setting.

Participant Groups

Group I: Cranial Electrotherapy Stimulation (CES) Experimental Treatment 1 Intervention

Alpha-Stim AID ® is an FDA-cleared device for the treatment of anxiety that delivers CES through two earclip electrodes.

Group II: Sham Cranial Electrotherapy Stimulation (CES) Placebo Group 1 Intervention

The device for sham stimulation is physically identical and delivers a non-therapeutic dose of stimulation to replicate salient features of device usage.

At-Home Stimulation is already approved in European Union, United States for the following indications:

Approved in European Union as Flow Neuroscience tDCS Device for:

• Depression

Approved in United States as Transcranial Direct Current Stimulation (tDCS) for:

• Experimental for depression, chronic pain, and PTSD

Who Is Running the Clinical Trial?

Electromedical Products International, Inc.

Lead Sponsor

Trials

6

Recruited

550+

University of North Carolina, Chapel Hill

Collaborator

Trials

1,588

Recruited

4,364,000+

Findings from Research

In a case series involving seven patients with various psychiatric disorders, combining self-administered transcranial direct current stimulation (tDCS) with a behavioral therapy app showed clinically significant improvements in depressive symptoms for five out of seven patients and in anxiety symptoms for five out of six patients after 6 weeks of treatment.

The tDCS treatment was well-tolerated, with only mild side effects reported, suggesting that this combination therapy could be a safe and effective option for managing depression and anxiety in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Home-based transcranial direct current stimulation in dual active treatments for symptoms of depression and anxiety: A case series. Sobral, M., Guiomar, R., Martins, V., et al.[2022]

Transcranial direct current stimulation (tDCS) significantly alleviated symptoms of generalized anxiety disorder (GAD) and depression in a semiprofessional athlete, as evidenced by decreased scores on the Beck Anxiety Index, Beck Depression Index, and Pittsburgh Sleep Quality Index after treatment.

Brain imaging techniques, including functional near-infrared spectroscopy (fNIRS) and functional magnetic resonance imaging (fMRI), demonstrated changes in prefrontal connectivity associated with tDCS treatment, indicating its potential as a safe and effective method for assessing brain activity in psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of tDCS on Depression and Comorbid Generalized Anxiety Disorder: A Brain Function Imaging Case Report. Wu, Y., Tang, L., Shi, X., et al.[2022]

Cranial Electrotherapy Stimulation (CES) using novel in-ear electrodes significantly reduced state-anxiety symptoms in a 3-week study with nonclinical volunteers, compared to a sham treatment.

EEG analysis revealed that CES increased theta power in the left frontal region and high-beta activity in specific brain areas, suggesting that CES may positively influence brain activity related to anxiety management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of cranial electrotherapy stimulation with novel in-ear electrodes on anxiety and resting-state brain activity: A randomized double-blind placebo-controlled trial. Kim, J., Kim, H., Kim, DH., et al.[2021]

Cranial electrotherapy stimulation (CES) is a safe and effective treatment for generalized anxiety disorder (GAD), showing significant improvements in both anxiety and depression symptoms over a treatment period of 6-12 weeks, with sustained remission observed at 12 and 24 weeks.

The study found that early reductions in anxiety symptoms predicted later improvements in depression, indicating that addressing anxiety first may be crucial for the overall effectiveness of CES in treating GAD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential effects of cranial electrotherapy stimulation on changes in anxiety and depression symptoms over time in patients with generalized anxiety disorder. Morriss, R., Price, L.[2021]

Cranial electrotherapy stimulation (CES) significantly reduced anxiety symptoms in patients with generalized anxiety disorder (GAD), with 50% of participants achieving a 50% decrease in anxiety scores after 6 weeks of treatment.

The treatment was generally safe, with mild adverse effects like headache and nausea reported, suggesting CES could be a viable option for managing anxiety in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of cranial electrotherapy stimulation for generalized anxiety disorder. Bystritsky, A., Kerwin, L., Feusner, J.[2022]

Cranial electrotherapy stimulation (CES) was tested as an add-on treatment for tic disorders (TD) in a study involving 62 patients aged 6-17 years, showing a reduction in tic severity after 4 weeks of treatment.

While both active CES and sham CES groups experienced improvements in tic severity, the difference was not statistically significant, suggesting that the observed benefits may be largely due to a placebo effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, randomized, sham-controlled study of cranial electrotherapy stimulation as an add-on treatment for tic disorders in children and adolescents. Wu, WJ., Wang, Y., Cai, M., et al.[2021]

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]

Low intensity transcranial electrical stimulation (TES) is considered safe, with no serious adverse events reported in over 18,000 sessions across various populations, including healthy individuals and patients with neurological or psychiatric conditions.

While moderate adverse events like skin burns from tDCS are rare, mild adverse events such as headaches and fatigue are more common, and the safety profile is consistent across different age groups and vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Antal, A., Alekseichuk, I., Bikson, M., et al.[2023]

In a study involving 43 individuals with generalized anxiety disorder (GAD) and comorbid depression, both the Unified Protocol (UP) and UP combined with transcranial direct current stimulation (tDCS) significantly reduced symptoms compared to a wait-list control group.

The combination of UP and tDCS resulted in greater reductions in anxiety, worry, and anxiety sensitivity compared to UP alone, suggesting that adding tDCS may enhance treatment effectiveness for individuals with GAD and depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Augmenting the unified protocol for transdiagnostic treatment of emotional disorders with transcranial direct current stimulation in individuals with generalized anxiety disorder and comorbid depression: A randomized controlled trial. Nasiri, F., Mashhadi, A., Bigdeli, I., et al.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Home-based transcranial direct current stimulation in dual active treatments for symptoms of depression and anxiety: A case series. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of tDCS on Depression and Comorbid Generalized Anxiety Disorder: A Brain Function Imaging Case Report. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of cranial electrotherapy stimulation with novel in-ear electrodes on anxiety and resting-state brain activity: A randomized double-blind placebo-controlled trial. [2021]

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

Differential effects of cranial electrotherapy stimulation on changes in anxiety and depression symptoms over time in patients with generalized anxiety disorder. [2021]

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

A pilot study of cranial electrotherapy stimulation for generalized anxiety disorder. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

A double-blind, randomized, sham-controlled study of cranial electrotherapy stimulation as an add-on treatment for tic disorders in children and adolescents. [2021]

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. Netherlands pubmed.ncbi.nlm.nih.gov

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Augmenting the unified protocol for transdiagnostic treatment of emotional disorders with transcranial direct current stimulation in individuals with generalized anxiety disorder and comorbid depression: A randomized controlled trial. [2021]