Clinical trial NCT03903068: Transcranial Alternating Current Stimulation Treating Post-stroke Depression
Official title: The Efficacy of Transcranial Alternating Current Stimulation for Treating Post-stroke Depression: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Post-stroke Depression
Keywords: transcranial alternating current stimulation
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
First posted: 2019-04-04
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Experiment Group: (NEXALIN ADI AC stimulators) vs Mock Group(pseudo-stimulators). Both require the same appearance, all kinds of buttons, buttons, lights, switches, settings, etc. are the same, but the pseudo-stimulator can not release current.
Primary purpose: TREATMENT

Brief summary: Post-stroke depression (PSD) is one of the most common complications after stroke, with a high prevalence. PSD can affect prognosis and rehabilitation of stroke, increase risks of mortality and suicide, and escalate the economic burden on individuals and society. Studies have shown that transcranial alternating current stimulation (tACS) can also be used to treat depression, insomnia and anxiety. So far, this stimulator has been approved by FDA. However, there have not been any reports on the use of tACS in the treatment of depression and PSD in China. In this trial, the efficacy and safety of the tACS will be assessed with the rigor methodology manner.

Detailed description: Patients with post-stroke depression (PSD) have more dysfunction, poorer recovery outcomes, and higher morbidity and mortality in the first year after stroke onset than those patients without stroke. Some therapeutic methods have shown to be effective for PSD, including antidepressants, non-drug interventions, and combination therapies. However, pharmacological agents not only show unwanted side effects, including nausea, diarrhea, fatigue, and dizziness, but also produce high risk of hemorrhagic complications and stroke. Therefore, in addition to antidepressants treating PSD, non-drug interventions have been proposed to treat PSD. Until now, there are various physical techniques, including transcranial magnetic stimulation, vagus nerve stimulation, transcranial direct current stimulation, transcranial ultrasonic stimulation, etc. Previous studies have shown that transcranial alternating current stimulation (tACS) is commonly used to relieve pain, and has also been used to treat conditions such as transient tic disorder and cluster headaches. In the brain, there are specific opioid receptors which are not independent, and they work together with the electro analgesic system. Patients treated for chronic pain had lower levels of endorphins in their cerebrospinal fluid. Theoretically, using tACS can alleviate pain was caused by electrical stimulation to activate the brain's pain system (anti-nociceptive system), led to the beta-endorphin, serotonin and norepinephrine release.

Therefore, the study is expected to verify the effect of Transcranial Alternating Current Stimulation on patients with PSD in China and preliminarily explore the variations of gamma and beta-oscillations and cognitive function for the intervention of PSD utilized by it.

Eligibility criteria: Inclusion Criteria:

1. A diagnosis of PSD is based on the "Depressive disorder due to another medical condition" of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V);
2. Age 18-70 years old, gender is not limited;
3. Right-handed;
4. More than 6 months after the onset of stroke;
5. The duration of depressive disorder persists for more than two weeks;
6. Having the Hamilton Depression Rating Scale 17-Item (HAMD-17) scores higher than 17 at baseline;
7. Absence of psychiatric disorder or family history of psychosis before stroke;
8. Has never taken antidepressants before enrollment;
9. Having the level of audiovisual for examinations required for the study;
10. Providing signed informed consent.

Exclusion Criteria:

1. Patients with life expectancy \< 6 months;
2. Severe or unstable organic diseases;
3. Acute brain injury and infection;
4. The impaired skin integrity at the electrode placement site or skin allergic to electrode gel or adhesive;
5. Active current suicidal intent or plan as shown by a score of ≥ 3 on the suicide item of HAMD-17;
6. Current participation in any other clinical trial,;
7. Prior exposure to all kinds of neuromodulation treatments (including electroconvulsive therapy, TMS, tDCS, etc);
8. Prior exposure to any implanted device in body (including a cochlear implant, cardiac pacemaker, an implanted device or metal in the brain);
9. A history of brain organic diseases (including seizures, hydrocephalus, and brain tumors);
10. Any situations the investigators believe that they are not suitable for this study.

Primary outcomes:
measure: the proportion of participants having an improvement at week 8
timeFrame: week 8
Secondary outcomes:
measure: The proportions of participants achieve an improvement in neurological function
timeFrame: weeks 4 and 8
measure: The proportions of participants achieve an improvement in independence
timeFrame: weeks 4 and 8
measure: The proportions of participants with a Barthel Index (BI) score of ≥ 90
timeFrame: weeks 4 and 8
measure: The proportions of participants having severity levels
timeFrame: weeks 4 and 8
measure: CGI-Improvement (CGI-I)
timeFrame: weeks 4 and 8
measure: the Hamilton Anxiety Rating Scale (HAMA)
timeFrame: weeks 4 and 8
measure: the Mini-Mental State Examination (MMSE)
timeFrame: weeks 4 and 8
measure: the Montreal Cognitive Assessment (MoCA)
timeFrame: weeks 4 and 8
measure: the proportion of participants having an improvement at week 4
timeFrame: week 4
measure: the changes of beta-and gamma-oscillations at weeks 4 and 8
timeFrame: weeks 4 and 8
measure: the variations of cognitive status at weeks 4 and 8
timeFrame: weeks 4 and 8
measure: the proportions of participants have an epileptic seizure at weeks 4 and 8
timeFrame: weeks 4 and 8
measure: the proportions of participants who have symptoms in the treatment-emergent symptom scale (TESS) at weeks 4 and 8
timeFrame: weeks 4 and 8
Other outcomes:
Locations:
city: Beijing
country: China
facility: Xuanwu Hospital, Capital Medical University
state: Beijing
Study officials:
affiliation: Xuanwu Hospital, Beijing
name: Haiqing Song, doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shen X, Liu M, Cheng Y, Jia C, Pan X, Gou Q, Liu X, Cao H, Zhang L. Repetitive transcranial magnetic stimulation for the treatment of post-stroke depression: A systematic review and meta-analysis of randomized controlled clinical trials. J Affect Disord. 2017 Mar 15;211:65-74. doi: 10.1016/j.jad.2016.12.058. Epub 2017 Jan 10.
citation: Gabis L, Shklar B, Baruch YK, Raz R, Gabis E, Geva D. Pain reduction using transcranial electrostimulation: a double blind "active placebo" controlled trial. J Rehabil Med. 2009 Mar;41(4):256-61. doi: 10.2340/16501977-0315.
citation: Wang H, Zhang W, Zhao W, Wang K, Wang Z, Wang L, Peng M, Xue Q, Leng H, Ding W, Liu Y, Li N, Dong K, Zhang Q, Huang X, Xie Y, Chu C, Xue S, Huang L, Yao H, Ding J, Zhan S, Min B, Fan C, Zhou A, Sun Z, Yin L, Ma Q, Baskys A, Jorge RE, Song H. The efficacy of transcranial alternating current stimulation for treating post-stroke depression: Study Protocol Clinical Trial (SPIRIT Compliant). Medicine (Baltimore). 2020 Apr;99(16):e19671. doi: 10.1097/MD.0000000000019671.