Effectiveness of CES on Emotional and Cellular Wellbeing

Depression Clinical Trial

Official title:

The Effect of Cranial Electrotherapy Stimulation on Emotional and Cellular Wellbeing

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03369418
• Other study ID #: 15-001639
• Status: Completed
• Phase: N/A
• Start date: March 2016
• Est. completion date: October 20, 2018

Study information

• Verified date: August 2020
• Source: University of California, Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: October 20, 2018
• Est. primary completion date: October 20, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Anxiety
• Depression

Intervention

Device:
• 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
• 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.

Locations

Country	Name	City	State
United States	University of California, Los Angeles (UCLA)	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Los Angeles

Country where clinical trial is conducted

United States, 

References & Publications (10)

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. Epub 2006 Apr 11. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Verhoeven JE, Révész 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HADS Questionnaire Combined Score	The Hospital anxiety and depression scale (HADS) evaluates symptoms of anxiety and depression, minimum 0 and maximum 52 with higher scores indicating more symptoms. A combined score it utilized as the primary outcome measure, summing the scores for anxiety and depression.	After completion of the study (1 year)
Secondary	Telomere Length	Telomere length will be determined using real time quantitative polymerase chain reaction (qPCR) methodology as described previously with minor modifications.30,31 Peripheral blood mononuclear cells (PBMC) are isolated and genomic DNA extracted. Using the standard curve method, cycle threshold (CT) values are plotted on a standard curve of human genomic DNA to estimate an ng/microliter concentration value. Telomere length values are expressed as the ratio of the estimated concentration generated by PCR of the telomere gene (T) divided by the hemoglobin single (S) copy gene = (T/S).	After completion of the study (1 year)