Effectiveness of CES on Emotional and Cellular Wellbeing

NCT ID: NCT03369418

Last Updated: 2020-08-19

Study Results

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Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

44 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-03-31

Study Completion Date

2018-10-20

Brief Summary

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The investigators aim to use a CES (cranial electrotherapy stimulation) intervention to improve emotional well-being by reducing symptoms of anxiety and depression and to assess for changes in markers of cellular health - specifically, telomere length and telomerase activity

Detailed Description

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This study aims to test an auricular cranial electrotherapy stimulation (CES) device, Alpha-Stim, to assess for changes in markers of cellular health and emotional well-being improvement associated with anxiety and depression.

Returning Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) Veterans have a high incidence of anxiety, depression, insomnia, post-traumatic stress disorder (PTSD) and chronic pain, leading to reductions in emotional well-being. This type of chronic emotional distress can lead to detrimental biological outcomes. We will compare as an exploratory outcome Veterans vs. non-Veterans response to Alpha-Stim treatment. At the cellular level, impairment of the telomere/telomerase system may be a result of this dysregulation, given the descriptions of shorter telomeres (a marker of cellular aging), as well as increased markers of inflammation in subjects with depression, anxiety and PTSD, compared to aged matched healthy populations. These negative cellular effects of emotional distress have not been well studied in this population and may offer significant benefit.

In one study of auricular CES using the same protocol proposed here, 115 patients with anxiety or anxiety and comorbid depression were studied over 5 weeks in a randomized, sham controlled trial, showing significant improvements in both anxiety and depression symptoms. Due to the complexity of overlapping negative affect symptoms that lead to impaired emotional well-being in Veterans, the investigators chose in this proposal to evaluate a composite measure of emotional distress (a combined anxiety and depression score) as the primary outcome. Beyond depression and anxiety, CES has been associated with reductions in insomnia and pain, both of which are also significant problems in Veterans, likely contributing to reduced emotional well-being.

Primarily all interested and appropriate study subjects will undergo a screening at the University of California, Los Angeles (UCLA) G. Oppenheimer Center for Neurobiology of Stress and Resilience (CNSR). The investigators expect to enroll and screen no less than 55 subjects in order to complete 22 evaluable subjects for analysis in each treatment group.

The Hospital Anxiety and Depression Scale (HADS) will assess symptom severity defined as normal range (0-7), mild (8-10), moderate (11-14) or severe (15-20). Subjects with impaired emotional well-being with mild to moderate anxiety and/or depression on the HADS scale will be included. Subjects with a maximum combined HADS score of 28 will be included. Subjects treated for anxiety, depression, psychiatric or mental health treatment must be on a stable regimen (pharmacological or non-pharmacological) for the past 3 months.

If eligible the study coordinator will contact them to schedule a screening visit at UCLA. During this visit, the research team will conduct baseline measurements via study questionnaires, history and physical exam, and a standardized psychiatric evaluation (MINI). Subjects meeting the inclusion criteria will have training in use of the Alpha-Stim device and will have their first 1 hour treatment. Subjects who tolerate the CES treatment will have blood drawn for biological measures and will take the device home to use daily for 8 weeks. Mid-study the subjects will come back to UCLA to complete questionnaires and have vital signs and weight measured. At the end of the 8 weeks, subjects will return to UCLA, return the device, have vital signs and weight measured, have the final blood draw, and complete a final set of questionnaires.

All in all, to complete the study, subjects will have an initial screening, mid and final study visit, pre, mid, and final study questionnaires, and blood drawn in the first and final visit.

Conditions

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Anxiety Depression

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
devices were masked at supplier and unblinded at end of the study.

Study Groups

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Active

Subjects will be given an Alpha-Stim active device for daily treatment. The electrodes attached to the device will be active. The device frequency is preset to 0.5 Hz and 100 microampere and treatment is one hour daily. The subjects will be instructed that the device is set to a low level so that the current is not detectable but should still be effective. The current will not be detectable in both active and sham devices in order for adequate blinding to occur.

Group Type ACTIVE_COMPARATOR

Alpha-Stim Active

Intervention Type DEVICE

The study device is a safe, commercially available take-home cranial electrotherapy stimulation device that applies an electrical current to a subject's head to treat anxiety, depression or insomnia

Inactive

Subjects will be given an Alpha-Stim inactive device for daily treatment. The electrodes attached to the device will be inactive. The device will not transmit anything when turned on because the electrodes are inactive. The frequency on the device will state 0.5 Hz and 100 microampere but it will not actually emit anything. Subjects in this group will receive "treatment" one hour daily. The subjects will be instructed that the device is set to a low level so that the current is not detectable but should still be effective. The current will not be detectable in both active and sham devices in order for adequate blinding to occur.

Group Type SHAM_COMPARATOR

Alpha-Stim Inactive

Intervention Type DEVICE

The study device given to the inactive group will be identical to the active except the electrodes attached to the device will be inactive. The device will not transmit anything when turned on because the electrodes are inactive.

Interventions

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Alpha-Stim Active

The study device is a safe, commercially available take-home cranial electrotherapy stimulation device that applies an electrical current to a subject's head to treat anxiety, depression or insomnia

Intervention Type DEVICE

Alpha-Stim Inactive

The study device given to the inactive group will be identical to the active except the electrodes attached to the device will be inactive. The device will not transmit anything when turned on because the electrodes are inactive.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

1. Male
2. Within the age range of 18-40 years old
3. Score 8-14 on either the anxiety or depression HADS scale as defined as mild (8-10) to moderate (11-14)
4. Subjects who receive anxiety, depression, psychiatric or mental health treatment (pharmacological or non-pharmacological) must be on a stable regimen for the past 3 months
5. No active suicidal ideation or psychosis (including schizophrenia and bipolar disorder)
6. No uncontrolled or progressive severe medical illness (e.g., cancer, uncontrolled diabetes mellitus, active cardiac disease)
7. No use of a pacemaker or any other implanted electrical device
8. No alcohol consumption greater than 2 units daily
9. Ability to independently complete the in-person study questionnaires and sign informed consent form (ICF) without assistance
10. Willing to comply with all study procedures and be available for the duration of the study
11. No participation in another clinical trial study

Exclusion Criteria

1. Not a male
2. Younger than 18 years old or older than 40 years old
3. Score ≥15 on either the anxiety or depression HADS scale as defined as severe (15-20)
4. Subject who receive anxiety, depression, psychiatric or mental health treatment (pharmacological or non-pharmacological) who have not been on a stable regimen for the past 3 months
5. Active suicidal ideation or psychosis (including schizophrenia and bipolar disorder)
6. History of inpatient treatment or suicidal ideation within the last year
7. Use of a pacemaker or any other implanted electrical device
8. Unable to independently complete the in-person study questionnaires and sign ICF due to impaired cognitive function
9. Unwilling to comply with all study procedures
10. Unavailable for the duration of the study
11. Current participation in another clinical trial study
12. Any other condition that the investigator believes would jeopardize the safety or rights of the subject or would render the subject unable to comply with the study protocol or make use of acquired data non-analyzable
Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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University of California, Los Angeles

OTHER

Sponsor Role lead

Responsible Party

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Kirsten Tillisch, MD

MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Kirsten Tillisch, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Locations

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University of California, Los Angeles (UCLA)

Los Angeles, California, United States

Site Status

Countries

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United States

References

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Verhoeven JE, Revesz D, Wolkowitz OM, Penninx BW. Cellular aging in depression: Permanent imprint or reversible process?: An overview of the current evidence, mechanistic pathways, and targets for interventions. Bioessays. 2014 Oct;36(10):968-78. doi: 10.1002/bies.201400068. Epub 2014 Aug 20.

Reference Type BACKGROUND
PMID: 25143317 (View on PubMed)

Simon NM, Smoller JW, McNamara KL, Maser RS, Zalta AK, Pollack MH, Nierenberg AA, Fava M, Wong KK. Telomere shortening and mood disorders: preliminary support for a chronic stress model of accelerated aging. Biol Psychiatry. 2006 Sep 1;60(5):432-5. doi: 10.1016/j.biopsych.2006.02.004. Epub 2006 Apr 11.

Reference Type BACKGROUND
PMID: 16581033 (View on PubMed)

van Ockenburg SL, de Jonge P, van der Harst P, Ormel J, Rosmalen JG. Does neuroticism make you old? Prospective associations between neuroticism and leukocyte telomere length. Psychol Med. 2014 Mar;44(4):723-9. doi: 10.1017/S0033291713001657. Epub 2013 Jul 9.

Reference Type BACKGROUND
PMID: 23834823 (View on PubMed)

Teyssier JR, Chauvet-Gelinier JC, Ragot S, Bonin B. Up-regulation of leucocytes genes implicated in telomere dysfunction and cellular senescence correlates with depression and anxiety severity scores. PLoS One. 2012;7(11):e49677. doi: 10.1371/journal.pone.0049677. Epub 2012 Nov 21.

Reference Type BACKGROUND
PMID: 23185405 (View on PubMed)

Jergovic M, Tomicevic M, Vidovic A, Bendelja K, Savic A, Vojvoda V, Rac D, Lovric-Cavar D, Rabatic S, Jovanovic T, Sabioncello A. Telomere shortening and immune activity in war veterans with posttraumatic stress disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2014 Oct 3;54:275-83. doi: 10.1016/j.pnpbp.2014.06.010. Epub 2014 Jun 28.

Reference Type BACKGROUND
PMID: 24977331 (View on PubMed)

Barclay TH, Barclay RD. A clinical trial of cranial electrotherapy stimulation for anxiety and comorbid depression. J Affect Disord. 2014 Aug;164:171-7. doi: 10.1016/j.jad.2014.04.029. Epub 2014 Apr 21.

Reference Type BACKGROUND
PMID: 24856571 (View on PubMed)

Kirsch DL, Nichols F. Cranial electrotherapy stimulation for treatment of anxiety, depression, and insomnia. Psychiatr Clin North Am. 2013 Mar;36(1):169-76. doi: 10.1016/j.psc.2013.01.006.

Reference Type BACKGROUND
PMID: 23538086 (View on PubMed)

Lande RG, Gragnani C. Efficacy of cranial electric stimulation for the treatment of insomnia: a randomized pilot study. Complement Ther Med. 2013 Feb;21(1):8-13. doi: 10.1016/j.ctim.2012.11.007. Epub 2012 Dec 21.

Reference Type BACKGROUND
PMID: 23374200 (View on PubMed)

Taylor AG, Anderson JG, Riedel SL, Lewis JE, Kinser PA, Bourguignon C. Cranial electrical stimulation improves symptoms and functional status in individuals with fibromyalgia. Pain Manag Nurs. 2013 Dec;14(4):327-335. doi: 10.1016/j.pmn.2011.07.002. Epub 2011 Oct 6.

Reference Type BACKGROUND
PMID: 24315255 (View on PubMed)

Lee SH, Kim WY, Lee CH, Min TJ, Lee YS, Kim JH, Park YC. Effects of cranial electrotherapy stimulation on preoperative anxiety, pain and endocrine response. J Int Med Res. 2013 Dec;41(6):1788-95. doi: 10.1177/0300060513500749.

Reference Type BACKGROUND
PMID: 24265330 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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15-001639

Identifier Type: -

Identifier Source: org_study_id

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