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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how cranial electrotherapy stimulation (CES), a non-invasive treatment using mild electrical currents, affects anxiety symptoms in individuals diagnosed with generalized anxiety disorder (GAD). Participants will use a device at home that sends small electrical currents through earclip electrodes. Two groups will participate: one receiving actual CES and another receiving a sham (fake) treatment. The study seeks individuals aged 18 to 21 diagnosed with GAD who experience mild to moderate anxiety symptoms. As an unphased trial, it offers a unique opportunity to contribute to understanding CES's potential benefits for anxiety.

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 prior data suggests that cranial electrotherapy stimulation (CES) is safe for treating generalized anxiety disorder?

Research has shown that cranial electrotherapy stimulation (CES) is generally safe. The FDA has approved the Alpha-Stim AID device for treating anxiety, confirming its safety. Studies have found that CES can effectively reduce anxiety symptoms, with some reports showing a 32% reduction. These studies also indicate that CES is well-tolerated, with no major side effects or adverse events reported. However, individual experiences may vary. It's important to consider personal health conditions and consult with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Cranial Electrotherapy Stimulation (CES) for generalized anxiety disorder because it offers a unique method of treatment that sets it apart from standard options like medication or therapy. CES uses a small device that delivers electrical stimulation through earclip electrodes, which is non-invasive and can be administered at home. This new approach targets brain activity directly, potentially offering quicker relief from anxiety symptoms without the side effects commonly associated with medications. Additionally, the ability to use CES at home provides increased accessibility and convenience for individuals seeking treatment for generalized anxiety disorder.

What evidence suggests that cranial electrotherapy stimulation (CES) is effective for generalized anxiety disorder?

Research shows that Cranial Electrotherapy Stimulation (CES) can help reduce anxiety symptoms. Studies indicate that CES moderately lowers anxiety in people with various anxiety disorders. It may also alleviate symptoms of anxiety and depression and improve sleep quality for older adults with generalized anxiety disorder (GAD). In this trial, some participants will receive CES using the Alpha-Stim AID device, which evidence supports as effective for treating anxiety and depression. Early research suggests CES might reduce anxiety symptoms in people with GAD. ^{1 2 3 6 7}

Who Is on the Research Team?

Samantha Meltzer-Brody, MD, MPH

Principal Investigator

University of North Carolina, Chapel Hill

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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) 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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9218324/

Efficacy and Tolerability of Cranial Electrotherapy Stimulation ... We found CES is effective in reducing anxiety symptoms with moderate effect size in patients with both primary and secondary anxiety.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0929664623004825

Effect of cranial electrotherapy stimulation as an add-on ... CES clinically reduces symptoms of anxiety and depression and may improve sleep quality in late-life GAD. Future randomized controlled study is needed.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02901080

Clinical and Cost Effectiveness of Alpha-Stim AID CES The primary objective of this study is to evaluate the clinical effectiveness of treatment with Alpha-Stim AID Cranial Electrotherapy Stimulations (CES) for ...

4. scirp.org scirp.org/journal/paperinformation?paperid=140015

Alpha-Stim AID Cranial Electrotherapy Stimulation (CES) ... Alpha-Stim AID cranial electrotherapy stimulation (CES) has evidence of effectiveness in the treatment of anxiety and depression.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/18348596/

A pilot study of cranial electrotherapy stimulation for ... This preliminary study suggests that CES may reduce symptoms of anxiety in GAD. We hope that these preliminary results will encourage further research.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02901080

Clinical and Cost Effectiveness of Alpha-Stim AID CES The primary objective of this study is to evaluate the clinical effectiveness of treatment with Alpha-Stim AID Cranial Electrotherapy Stimulations (CES) for ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7882621/

A Critical Review of Cranial Electrotherapy Stimulation for ... A recent open consecutive cohort study demonstrated improvement in anxiety and depression symptoms of generalized anxiety order following 12 and ...