Anxiety, Depression
Conditions
Brief 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
Detailed 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.
Interventions
DEVICEAlpha-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
DEVICEAlpha-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.
Sponsors
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
devices were masked at supplier and unblinded at end of the study.
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HADS Questionnaire Combined Score | After completion of the study (1 year) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Telomere Length | After completion of the study (1 year) | 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). |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited by flyers from the WLA VA Integrative Medicine Clinics and on the UCLA campus between April 2016 and August 2018.
Participants by arm
| Arm | Count |
|---|---|
| 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.
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 | 13 |
| 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.
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. | 11 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 3 | 3 |
Baseline characteristics
| Characteristic | Inactive | Total | Active |
|---|---|---|---|
| Age, Continuous | 27.09 years STANDARD_DEVIATION 5.72 | 27.92 years STANDARD_DEVIATION 6.52 | 28.62 years STANDARD_DEVIATION 7.29 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) White | 5 Participants | 12 Participants | 7 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 11 Participants | 24 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 11 |
| other Total, other adverse events | 2 / 13 | 6 / 11 |
| serious Total, serious adverse events | 0 / 13 | 0 / 11 |
Outcome results
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.
Time frame: After completion of the study (1 year)
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Active | HADS Questionnaire Combined Score | Baseline estimated means | 20.3077 score on a scale | Standard Error 1.65 |
| Active | HADS Questionnaire Combined Score | Post treatment estimated mean | 11.1538 score on a scale | Standard Error 1.65 |
| Inactive | HADS Questionnaire Combined Score | Baseline estimated means | 19.909 score on a scale | Standard Error 1.79 |
| Inactive | HADS Questionnaire Combined Score | Post treatment estimated mean | 15.4545 score on a scale | Standard Error 1.79 |
p-value: 0.013t-test, 1 sided
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).
Time frame: After completion of the study (1 year)
Population: 2 subjects had inadequate samples for analysis of telomere length, both in the active arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Telomere Length | .6945 T/S | Standard Error 0.03231 |
| Inactive | Telomere Length | .7841 T/S | Standard Error 0.03487 |
p-value: 0.33t-test, 1 sided