Clinical trial NCT05622552: Effect of tDCS Combined With Pharmacological Treatments for Bipolar Mania
Official title: Study on the Efficacy of tDCS Combined With Pharmacological Treatments on Manic Episodes and Its Effect on Brain Function
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Manic Episode
Keywords: manic episode
Transcranial direct current stimulation
tDCS
Functional near-infrared spectroscopy
fNIRS
Lead sponsor: Shanghai Mental Health Center
Sponsor class: OTHER
First posted: 2022-11-18
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: tDCS stimulation, which was performed once a day sessions of active or sham anodal tDCS to the right dorsolateral prefrontal cortex and cathode to the left OFC (2 mA, 20 minutes, 10 sessions).

In the active group, current stimulations were gradually ramped up to 2 mA (in 30 seconds) intensity for 20 minutes, once a day, for 10 days. For sham stimulation, the procedure was identical, except that the current was gradually ramped up to 2mA and rapidly down to zero (in 30 seconds), thus leading to the same initial sensations of tDCS.
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to conduct a randomized double-blind controlled trial to explore the efficacy and safety of transcranial direct current stimulation (tDCS) in the treatment of manic episode (ME) and analyzes the brain functional connectivity to construct the therapeutic effect prediction model of tDCS for ME.

The main questions it aims to answer are:

* A randomized double-blind controlled trial is conducted to clarify the efficacy and safety of tDCS combined with pharmacological treatments in the ME.
* A therapeutic effect prediction model of tDCS for ME by using functional near-infrared spectroscopy to evaluate brain function.

Participants will be receive:

* clinical data interview and clinical symptom assessment.
* the functional near-infrared spectroscopy (fNIRS) to analysis brain functional connectivity.
* tDCS stimulation, which was performed once a day sessions of active or sham anodal tDCS to the right dorsolateral prefrontal cortex and Cathode to the left OFC (2 mA, 20 minutes, 10 sessions).

In the active group, current stimulations were gradually ramped up to 2 mA (in 30 seconds) intensity for 20 minutes, once a day, for 10 days. For sham stimulation, the procedure was identical, except that the current was gradually ramped up to 2mA and rapidly down to zero (in 30 seconds), thus leading to the same initial sensations of tDCS.

Detailed description: Manic Episode (ME) is a form of bipolar disorder, characterized by a distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased goal-directed activity or energy, lasting at least 1 week and present most of the day, nearly every day (or any duration if hospitalization is necessary). Transcranial direct current stimulation (tDCS), which uses weak current to stimulate specific brain areas, is a non-invasion neuromodulation.

This study intends to conduct a randomized double-blind controlled trial to explore the efficacy and safety of right dorsolateral prefrontal cortex stimulation (R-DLPFC) in the treatment of ME. In addition, the brain functional connectivity was analyzed by machine learning analysis based on the brain function detection data, and the therapeutic effect prediction model of tDCS for ME was constructed to provide a basis for the precise navigation and individualized treatment of ME by tDCS.

70 patients with manic episode diagnosed by the Structured Clinical Interview for DSM-IV, Axis I Disorders, Patient Version (SCID-I/P) were recruited from the Shanghai Mental Health Center. Written, informed and competent consent was obtained before their participation in the study and a structured interview would be completed.

After strict inclusion and exclusion criteria for participants, clinical data interview and clinical symptom assessment will be conducted by a trained psychiatrists at the Shanghai Mental Health Center. And the functional near-infrared spectroscopy (fNIRS) would be used to analysis brain functional connectivity at the baseline and the end of the 10 seesions. The study would randomize all participants in a 1:1 ratio, one was "active group", and the other was "sham group". The anode of tDCS was placed over right dorsolateral prefrontal cortex (R-DLPFC) and the cathode to the left orbitofrontal cortex (OFC). In the active group, current stimulations were gradually ramped up to 2 mA (in 30 seconds) intensity for 20 minutes, once a day, for 10 days. For sham stimulation, the procedure was identical, except that the current was gradually ramped up to 2mA and rapidly down to zero (in 30 seconds), thus leading to the same initial sensations of tDCS. The study was 8 weeks long, and procedure of visit would be occurred at the following time points: baseline, week 2, 4 and 8.At each visit, psychometric outcome measures including the Young Manic Rating Scale (YMRS), Montgomery-Åsberg Depression Rating Scale (MADRS), Quick Inventory of Depressive Symptomatology (QIDS SR-16), Altman Self-Rating Mania Scale (ASRM), Wisconsin Card Sorting Test (WCST), Stroop Color Word Test, Morisky Medication Adherence Scale-8 (MMAS-8), Global Assessment of Functioning (GAF).The reduction in YMRS after 10 sessions of tDCS was the primary outcome.

The study will require active reporting of adverse effects from the participants, as well as reports from observations of researchers.

Eligibility criteria: Inclusion Criteria:

* 1. Manic episode in patient with bipolar disorder, as assessed by the Structured Clinical Interview for DSM-IV, Axis I Disorders, Patient Version (SCID-I/P).
* 2. Young Mania Rating Scale (YMRS) score above or equal 13.
* 3. Patients of both genders between 18 and 65 years of age (when obtaining informed consent) ,right-handed.
* 4. Junior high school education and above, with understanding of the content of the study.
* 5. Written, informed and competent consent was obtained before participation in the study.
* 6. The regimens and dosages of mood stabilizers and atypical antipsychotics remained stable from the start of tDCS to the completion of 10 tDCS sessions. One mood stabilizer and/or one atypical antipsychotics could be administered, and no new or discontinued drugs were added
* 7. Did not receive other trials of neurostimulation treatments (include tCS, rTMS, MECT.etc) and psychotherapies 1 month before tDCS treatment to 2 weeks after the end of treatment.
* 8. Benzodiazepines and antidepressants were not used from 1 month before tDCS treatment to 2 weeks after the end of treatment.

Exclusion Criteria:

* 1. Laboratory abnormalities that are judged to be clinically significant and that clinicians consider to affect the efficacy of the trial or the safety of the subjects.
* 2. With severe or unstable diseases, including: Patients with neurological diseases (delirium, dementia, stroke, epilepsy, migraine, high intracranial pressure, craniocerebral surgery, etc.), congestive heart failure, angina pectoris, myocardial infarction, arrhythmia, hypertension (including untreated or uncontrolled hypertension), apnea syndrome, malignant tumors, immunocompromised subjects, acute or chronic liver and kidney failure, cirrhosis or active liver disease, Or blood glucose higher than 12mmol/L.
* 3.Alcohol or drug dependence within 6 months before the trial.
* 4.Pregnant and lactating women. Male and female subjects who are not using effective contraception or who plan to become pregnant within 3 months of starting the trial.
* 5.Family history of epilepsy (within three generations).
* 6.History of head trauma or craniocerebral surgery such as open wound or skull repair.
* 7.Other conditions that were not appropriate for participation in the clinical trial.

Primary outcomes:
measure: the reduction in YMRS after two weeks of study
timeFrame: two weeks of study
Secondary outcomes:
measure: the scale of MADRS
timeFrame: each visit of study in 8 weeks
measure: the scale of QIDS-16
timeFrame: each visit of study in 8 weeks
measure: the scale of ASRM
timeFrame: each visit of study in 8 weeks
measure: the scale of WCST
timeFrame: each visit of study in 8 weeks
measure: the scale of Stroop Color Word Test
timeFrame: each visit of study in 8 weeks
measure: the scale of MMAS-8
timeFrame: each visit of study in 8 weeks
measure: the scale of GAF
timeFrame: each visit of study in 8 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Mental Health Center
state: Shanghai
Study officials:
affiliation: Shanghai Mental Health Center
name: Dongbin Lyu, MBBS
role: PRINCIPAL_INVESTIGATOR
References: