Active CR for Stress, Anxiety, and Insomnia

Overseen By Study Coordinator

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Wake Forest University Health Sciences

Disqualifiers: Alcohol, Recreational drugs, Seizure disorder, others

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

Compensation: Varies

Number of Visits: 9

Duration: 6-12 weeks

150 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does exclude those using alcohol or recreational drugs.

What data supports the effectiveness of the treatment Cereset Research, Cereset, BrainEcho, HIRREM for stress, anxiety, and insomnia?

Research suggests that HIRREM, a part of the treatment, may help with insomnia, as a study showed significant improvement in sleep quality for participants with moderate-to-severe insomnia. Additionally, Cereset Research has been shown to improve insomnia in a trial for postconcussive symptoms, indicating potential benefits for related conditions. ^{1 2 3 4 5}

How does the Cereset treatment differ from other treatments for stress, anxiety, and insomnia?

Cereset is unique because it uses a non-invasive approach that involves listening to brainwave echoes to help the brain relax and reset itself, unlike traditional treatments that may involve medication or cognitive therapy. ^{6 7 8 9 10}

What is the purpose of this trial?

This trial is testing a treatment called Cereset Research that uses sounds reflecting brain activity to help people aged 11 or older who have stress, anxiety, or insomnia. The sounds aim to balance the brain and improve automatic body functions.

Research Team

Charles Tegeler, MD

Principal Investigator

Wake Forest University Health Sciences

Eligibility Criteria

This trial is for individuals experiencing stress, anxiety, or insomnia with certain scores on related self-reported inventories. Participants must be able to follow instructions and sit still with sensor leads attached. Excluded are those over 285 pounds, severe hearing impairment, using alcohol/drugs, or have used similar brainwave technologies recently.

Inclusion Criteria

I have stress, anxiety, or insomnia with qualifying scores on specific health questionnaires.

I can follow simple instructions and sit still with sensor leads attached.

Exclusion Criteria

You have serious difficulty hearing (because you will need to use ear buds during the clinical trial).

I weigh more than 285 pounds.

I have used HIRREM, Brainwave Optimization, Cereset, or similar devices.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive between 6 and 12 sessions of audible tones echoing current brainwave activity (CR)

6-12 weeks

6-12 visits (in-person)

Follow-up

Participants are monitored for changes in physiological and self-reported outcomes after treatment

4-6 weeks

2 visits (in-person)

Treatment Details

Interventions

• Cereset Research

Trial Overview The study tests Cereset Research (CR), a method aimed at improving autonomic function in people with stress-related symptoms. It involves sitting comfortably while connected to sensor leads that presumably help balance brain rhythms associated with stress and sleep issues.

Participant Groups

Group I: Experimental: Active CR Experimental Treatment 1 Intervention

For this single arm, open label, exploratory trial this will be the intervention arm using active CR.

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

The Susanne Marcus Collins Foundation, Inc

Collaborator

Trials

2

Recruited

290+

The Susanne Marcus Collins Foundation, Inc.

Collaborator

Trials

5

Recruited

430+

Findings from Research

A patient with insomnia related to generalized anxiety disorder successfully used High-Resolution, Relational, Resonance-Based, Electroencephalic Mirroring (HIRREM) therapy alongside escitalopram, leading to the resolution of insomnia after stopping the medication.

Despite only one randomized clinical trial supporting HIRREM for insomnia and its lack of FDA approval for this use, the case highlights the importance of patient education and informed decision-making regarding alternative therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Treatment of Insomnia Secondary to Generalized Anxiety Disorder: Evaluating Escitalopram Use With Concomitant High-Resolution, Relational, Resonance-Based, Electroencephalic Mirroring (HIRREM). Sawar, K., Pavar, G., Xu, N., et al.[2023]

HIRREM™ is a noninvasive EEG-based intervention that significantly reduced insomnia severity in a pilot study of 20 participants, showing a drop of 10.3 points on the Insomnia Severity Index (ISI) after treatment, with effects lasting over 4 weeks.

The study found no adverse events associated with HIRREM, indicating it is a safe option for treating moderate-to-severe insomnia, and suggests the need for larger controlled trials to further evaluate its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open label, randomized, crossover pilot trial of high-resolution, relational, resonance-based, electroencephalic mirroring to relieve insomnia. Tegeler, CH., Kumar, SR., Conklin, D., et al.[2021]

The study involved 106 military service members, veterans, or their spouses with persistent postconcussive symptoms, and found that 10 sessions of acoustic stimulation significantly reduced symptoms as measured by the Neurobehavioral Symptom Inventory (NSI) from a baseline score of 41.0 to 27.2 (P < 0.0001).

However, there was no significant difference in symptom reduction between the group receiving brainwave-linked tones and the sham control group, indicating that while acoustic stimulation is beneficial, the specific method of linking tones to brain activity did not enhance efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, controlled clinical trial of acoustic stimulation to reduce postconcussive symptoms. Cole, WR., Tegeler, CL., Choi, YS., et al.[2023]

In a study involving five rats, microinjections of corticotropin-releasing factor (CRF) into the amygdala showed that only the lowest dose (1 ng) significantly altered rapid eye movement sleep (REMS) within four hours post-injection.

The findings suggest that the changes in REMS following psychological stress may be influenced by the release of CRF in the central nucleus of the amygdala, highlighting a potential mechanism linking stress to sleep disturbances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corticotropin-releasing factor microinjection into the central nucleus of the amygdala alters REM sleep. Pawlyk, AC., Sanford, LD., Brennan, FX., et al.[2020]

Sleep disturbances, especially insomnia, are common in anxiety disorders, and they can even be part of the diagnostic criteria for conditions like generalized anxiety disorder and posttraumatic stress disorder.

While some studies show changes in sleep patterns related to anxiety disorders, there is no consistent sleep architecture profile for these disorders, indicating that individual differences and other factors like illness severity may influence sleep disturbances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleep and anxiety disorders. Staner, L.[2023]

Chronic insomnia is linked to increased levels of ACTH and cortisol, indicating heightened arousal in the body, which was observed in a study of 11 insomniacs compared to 13 healthy controls over 4 nights.

The findings suggest that insomnia is more about central nervous system hyperarousal rather than just sleep loss, highlighting the need for treatments that reduce overall physiological and emotional arousal, as insomniacs may be at risk for mental health issues and other medical problems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic insomnia is associated with nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: clinical implications. Vgontzas, AN., Bixler, EO., Lin, HM., et al.[2022]

Chronic insomnia with objectively short sleep duration is linked to severe health risks, including hypertension, diabetes, and neurocognitive impairment, indicating it is a biologically severe form of the disorder.

In contrast, insomnia with normal sleep duration is less severe and more likely to improve on its own, suggesting that different treatment approaches may be needed based on the type of insomnia, with biological treatments for short sleep duration and psychological interventions for normal sleep duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insomnia with objective short sleep duration: the most biologically severe phenotype of the disorder. Vgontzas, AN., Fernandez-Mendoza, J., Liao, D., et al.[2022]

High sleep reactivity, which is how much stress disrupts sleep, is linked to an increased risk of developing insomnia, shift-work disorder, and mental health issues like depression and anxiety, highlighting its importance in predicting future sleep problems.

Understanding sleep reactivity can help identify individuals at risk for severe insomnia and guide treatment options, as those with high reactivity may require different levels of intervention based on their specific sleep challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of stress on sleep: Pathogenic sleep reactivity as a vulnerability to insomnia and circadian disorders. Kalmbach, DA., Anderson, JR., Drake, CL.[2020]

Research suggests that primary insomnia may share neuroendocrine and clinical features with major depressive disorder, particularly involving the hypothalamic-pituitary-adrenal (HPA) axis and corticotropin releasing factor (CRF) overactivity.

The findings indicate that targeting HPA axis overactivity and CRF levels could be a potential strategy for managing chronic primary insomnia, possibly through the use of antiglucocorticoid agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insomnia: pathophysiology and implications for treatment. Roth, T., Roehrs, T., Pies, R.[2022]

In a study of seven male patients with severe chronic primary insomnia, evening and nocturnal cortisol levels were significantly higher compared to matched controls, suggesting an altered HPA-axis function in insomnia.

The study found that increased evening cortisol levels correlated with more nocturnal awakenings, indicating a potential vicious cycle where disturbed HPA functions contribute to the persistence of chronic insomnia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interactions between evening and nocturnal cortisol secretion and sleep parameters in patients with severe chronic primary insomnia. Rodenbeck, A., Huether, G., Rüther, E., et al.[2022]

References

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

The Treatment of Insomnia Secondary to Generalized Anxiety Disorder: Evaluating Escitalopram Use With Concomitant High-Resolution, Relational, Resonance-Based, Electroencephalic Mirroring (HIRREM). [2023]

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

Open label, randomized, crossover pilot trial of high-resolution, relational, resonance-based, electroencephalic mirroring to relieve insomnia. [2021]

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

Randomized, controlled clinical trial of acoustic stimulation to reduce postconcussive symptoms. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Corticotropin-releasing factor microinjection into the central nucleus of the amygdala alters REM sleep. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Sleep and anxiety disorders. [2023]

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

Chronic insomnia is associated with nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: clinical implications. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Insomnia with objective short sleep duration: the most biologically severe phenotype of the disorder. [2022]

8. England pubmed.ncbi.nlm.nih.gov

The impact of stress on sleep: Pathogenic sleep reactivity as a vulnerability to insomnia and circadian disorders. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Insomnia: pathophysiology and implications for treatment. [2022]

10. Ireland pubmed.ncbi.nlm.nih.gov

Interactions between evening and nocturnal cortisol secretion and sleep parameters in patients with severe chronic primary insomnia. [2022]