Cranial Electrotherapy Stimulation for Anxiety

Overseen By Amanda Crawford, MSHS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: David Moss

Must not be taking: Antipsychotics, Seizure medications

Disqualifiers: Bipolar, Schizophrenia, Nicotine, Pregnancy, 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: 8

Duration: 6 weeks

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a device called Alpha-Stim 100 can reduce symptoms of generalized anxiety. Participants will use either the real device or a sham (placebo) version for 40 minutes daily over six weeks to determine any difference in anxiety relief. The trial is open to active duty military members or Department of Defense beneficiaries who can access care at Nellis Air Force Base and are experiencing significant anxiety symptoms. As an unphased trial, it offers participants the chance to contribute to innovative research that could lead to new anxiety treatments.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot participate if you have started, changed, or stopped using any antidepressant or anxiety medication in the past four weeks. Also, you cannot be on antipsychotic or seizure medications.

What prior data suggests that this cranial electrotherapy stimulation is safe for treating anxiety?

Research has shown that the Alpha-Stim 100, a device for cranial electrotherapy stimulation (CES), is generally safe and easy to use. Studies have found that it can help with anxiety and sleep issues, and the FDA has approved it for these purposes. Reports from past studies indicate that negative side effects are rare and usually mild, such as slight skin irritation or headaches. This suggests that the treatment is safe for most people. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Cranial Electrotherapy Stimulation (CES) for anxiety is unique because it uses a small, portable device called Alpha-Stim 100 that delivers a low-level electrical current to the brain. Unlike standard treatments like medication or psychotherapy, CES offers a non-invasive, drug-free option that targets the brain's electrical activity to help reduce anxiety. Researchers are excited about this treatment because it can be easily used at home, providing a convenient and potentially faster-acting solution compared to more traditional therapies.

What evidence suggests that cranial electrotherapy stimulation is effective for anxiety?

Research has shown that the Alpha-Stim 100 device, which participants in this trial may receive, can help reduce anxiety symptoms. A review of studies has highlighted its benefits for treating anxiety, depression, and sleep disturbances. Specifically, research found that Alpha-Stim can assist individuals with moderate to severe generalized anxiety disorder. The device sends small electrical currents to the brain, calming the nervous system. Although more research is needed, these findings suggest that Alpha-Stim could be a useful tool for managing anxiety. Participants in this trial will receive either the active Alpha-Stim treatment or a sham comparator to evaluate its effectiveness. ^{2 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for active duty military and DoD beneficiaries over 18 who can receive care at Nellis Air Force Base. Participants must show signs of anxiety with specific scores on the MINI and GAD-7 assessments.

Inclusion Criteria

You need to be able to receive medical care at Nellis Air Force Base to join this study.

I have been diagnosed with moderate to severe anxiety.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either active or sham CES treatment at home for 40 minutes daily

6 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Alpha-Stim 100
• Sham Comparator

Trial Overview The study tests Alpha-Stim 100, a device providing Cranial Electrotherapy Stimulation (CES), against a sham device to see if it helps reduce anxiety symptoms in participants.

How Is the Trial Designed?

Group I: Group 1: Active CES Experimental Treatment 1 Intervention

Active CES treatment at home 40 minutes daily for 6 weeks

Group II: Group 2: Sham CES Placebo Group 1 Intervention

Sham CES treatment at home 40 minutes daily for 6 weeks

Alpha-Stim 100 is already approved in European Union, United States for the following indications:

Approved in European Union as Alpha-Stim AID for:

• Anxiety
• Insomnia
• Depression

Approved in United States as Alpha-Stim AID for:

• Anxiety
• Insomnia

Approved in United States as Alpha-Stim M for:

• Anxiety
• Insomnia
• Pain

Who Is Running the Clinical Trial?

David Moss

Lead Sponsor

Trials

6

Recruited

830+

Published Research Related to This Trial

Cranial electrotherapy stimulation is an effective treatment for anxiety, depression, and insomnia, supported by over 40 years of research and more than 100 clinical studies.

The device has a very low incidence of adverse effects (less than 1%), which are generally mild and self-limiting, making it a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cranial electrotherapy stimulation for treatment of anxiety, depression, and insomnia. Kirsch, DL., Nichols, F.[2022]

Cranial electrotherapy stimulation (CES) significantly reduced anxiety symptoms in a study of 40 inpatient alcohol and/or polydrug users compared to sham treatment and routine controls, indicating its efficacy as a treatment option.

The study found no differences in treatment response based on age or type of substance abuse, and importantly, there was no placebo effect observed, suggesting that CES provides a genuine therapeutic benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cranial electrotherapy stimulation as a treatment for anxiety in chemically dependent persons. Schmitt, R., Capo, T., Boyd, E.[2019]

A study involving 47 university students showed that Alpha-Stim cranial electrostimulation (CES) delivered through a nurse-led clinic was highly accepted, with 97.9% completing the 6-week treatment, and resulted in significant reductions in anxiety and depression symptoms as measured by GAD-7 and PHQ-9 scales.

Alpha-Stim CES was found to be a cost-effective alternative to usual family doctor care, providing a feasible and safe home-based treatment option for students, with no adverse effects reported and only one participant experiencing a clinically important deterioration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility, acceptability and costs of nurse-led Alpha-Stim cranial electrostimulation to treat anxiety and depression in university students. Royal, S., Keeling, S., Kelsall, N., et al.[2022]

The Alpha-Stim AID device, which uses cranial electrotherapy stimulation (CES), is being tested for its effectiveness in reducing moderate to moderately severe depressive symptoms in a randomized controlled trial involving treatment-seeking patients aged 16 and older.

This study aims to determine if daily use of the Alpha-Stim AID device for 8 weeks can lead to significant and lasting reductions in depression symptoms, potentially offering a new, accessible treatment option for patients who may not respond to traditional antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised controlled trial investigating the clinical and cost-effectiveness of Alpha-Stim AID cranial electrotherapy stimulation (CES) in patients seeking treatment for moderate severity depression in primary care (Alpha-Stim-D Trial). Patel, S., Boutry, C., Patel, P., et al.[2022]

A meta-analysis of 23 studies involving 2959 children with ADHD found that treatment with psychostimulants significantly reduced the risk of anxiety compared to placebo, with a relative risk of 0.86.

Higher doses of psychostimulants were associated with an even lower risk of anxiety, suggesting that the benefits of treating ADHD symptoms may outweigh the potential for increased anxiety in some children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-Analysis: Reduced Risk of Anxiety with Psychostimulant Treatment in Children with Attention-Deficit/Hyperactivity Disorder. Coughlin, CG., Cohen, SC., Mulqueen, JM., et al.[2018]

The novel compound ACH-000029 shows promising anxiolytic effects comparable to existing treatments like benzodiazepines and serotonin reuptake inhibitors, acting on specific serotonergic and adrenergic receptors.

Safety assessments indicated no significant concerns at doses up to 50 mg/kg, supporting its potential as a new treatment for anxiety disorders without the side effects commonly associated with traditional anxiolytics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical characterization of ACH-000029, a novel anxiolytic compound acting on serotonergic and alpha-adrenergic receptors. Azevedo, H., Ferreira, M., Costa, RW., et al.[2020]

Atomoxetine significantly reduces ADHD symptoms in children and adolescents, especially in those with co-existing conditions like anxiety and depression, with a number needed to treat of 3.4-5.

While most side effects are mild and temporary, serious risks include increased vascular tone, decreased growth rate, and heightened suicidal behavior, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Atomoxetine for treatment of children and adolescents with ADHD]. Resen, K., Pagsberg, AK., Jörgens, G.[2017]

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]

In a study of 34 youth with anxiety disorders undergoing 8 sessions of cognitive-behavioral therapy, electrodermal activity (EDA) was found to provide valuable insights into emotional arousal, which did not align with self-reported distress levels (SUDS).

The results indicated that higher sympathetic arousal measured by EDA was associated with poorer treatment outcomes, suggesting that incorporating physiological assessments like EDA could enhance monitoring and effectiveness of exposure therapy for children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How anxious is too anxious? State and trait physiological arousal predict anxious youth's treatment response to brief cognitive behavioral therapy. McCormack, CC., Mennies, RJ., Silk, JS., et al.[2020]

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]

A 4-week cranial electrotherapy stimulation (CES) intervention showed significant reductions in sensory sensitivity, anxiety, and emotion dysregulation among 263 participants aged 4-24 with neurodevelopmental disorders, indicating its potential efficacy as a therapeutic tool.

The study reported a high completion rate of 75% and good tolerance and satisfaction scores, suggesting that CES is a feasible and well-accepted treatment option for behavioral regulation issues in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Open-Label Study of Cranial Electrotherapy Stimulation on Behavioral Regulation in a Mixed Neurodevelopmental Clinical Cohort. Brandes-Aitken, A., Gerdes, M., Hattangadi, N., et al.[2023]

In a well-conducted trial involving 236 participants with major depression, the Alpha-Stim AID device was found to be safe, with only 7% reporting adverse events, but it did not show any significant clinical effectiveness compared to a sham device.

Both the active and sham groups experienced similar reductions in depression symptoms, indicating that the Alpha-Stim AID device is not more effective than placebo in treating major depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical effectiveness of active Alpha-Stim AID versus sham Alpha-Stim AID in major depression in primary care in England (Alpha-Stim-D): a multicentre, parallel group, double-blind, randomised controlled trial. Morriss, R., Patel, S., Boutry, C., et al.[2023]

Citations

1. thelancet.com thelancet.com/journals/lanpsy/article/PIIS2215-0366(23)00007-X/fulltext

Clinical effectiveness of active Alpha-Stim AID versus sham ... We investigated whether active Alpha-Stim AID is superior to sham Alpha-Stim AID in terms of clinical effectiveness for depression symptoms in major depression.

2. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK493135/

The Effectiveness and Risks of Cranial Electrical Stimulation ... The Effectiveness and Risks of Cranial Electrical Stimulation for the Treatment of Pain, Depression, Anxiety, PTSD, and Insomnia: A Systematic Review [Internet] ...

3. alpha-stim.com alpha-stim.com/wp-content/uploads/2019/04/Alpha-Stim-M-Clinical-Evaluation-4.25.19.pdf?srsltid=AfmBOoq8kKlI39ZjCTA5eK083QL91jiHnu1Do_42wzjjwuJAjrUbdTBB

Scientific and Clinical Literature Examination for the ... effectiveness of anxiety, insomnia, depression and headache. PTSD data included Service. Members and Veterans only. The 2011 Alpha-Stim® Service Members and ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2772598723000429

A qualitative exploration of participant experiences of using ... A recent meta-analysis of five randomised controlled trials reported that Alpha-Stim AID is effective for managing depression in the community with a small to ...

5. alpha-stim.com alpha-stim.com/research-and-reports/clinical-effectiveness-and-cost-minimisation-model-of-alpha-stim-cranial-electrotherapy-stimulation-in-treatment-seeking-patients-with-moderate-to-severe-generalised-anxiety-disorder/?srsltid=AfmBOoojdkZeVTl8DJIefDfHvg5bM71PFgSCgLCZiYfj8sKo0GkZV2tP

Clinical effectiveness and cost minimisation model of ... Clinical effectiveness and cost minimisation model of Alpha-Stim cranial electrotherapy stimulation in treatment seeking patients with moderate to severe ...

6. alpha-stim.com alpha-stim.com/indications-and-risks/?srsltid=AfmBOooDbci9kicmp0t4DLlhmEF7YrWJ1VzBvGulF0Xng0yhcvXSBv0C

Indications and Risks The Alpha-Stim AID is a precision medical device used for cranial electrotherapy stimulation for the treatment of anxiety and insomnia.

7. alpha-stim.com alpha-stim.com/wp-content/uploads/2016/12/Alpha-Stim-Clinical-Examination-Report.pdf?srsltid=AfmBOoqDN-lgBkcCpe9BKsFAga_zNT-37JvZxZN2t94-Cil1LXJ6jwUn

M Microcurrent and Cranial Electrotherapy Stimulator The Alpha-Stim® M has US FDA 510(k) premarket clearance and has Underwriter Laboratories. (UL) Safety Standards Certification in the US for the treatment of ...

8. hsrd.research.va.gov hsrd.research.va.gov/publications/esp/CES.pdf

The Effectiveness and Risks of Cranial Electrical Stimulation ... Patients were randomly assigned to an active. Alpha-Stim 100 CES unit or a unit made inactive by the manufacturer, and told to treat themselves daily for one ...