Major Depressive Disorder
Conditions
Keywords
tDCS
Brief summary
A two-center trial to investigate whether or not active stimulation with the Flow FL-100 tDCS device is superior to sham stimulation for the treatment of major depressive disorder when used at home. Participants perform up to 36 tDCS sessions by themselves without supervision during a blinded 10-week phase, and then 30 more sessions during an unblinded open-label phase.
Interventions
DEVICETranscranial direct current stimulation
Transcranial direct current stimulation (tDCS) a non-invasive brain stimulation technique where a weak direct current (2 mA) is applied on the scalp through electrodes. The current modulates the underlying neural activity. The sessions are 30 minutes, 3-5 time a week.
DEVICESham Transcranial direct current stimulation
To blind the participants of the stimulation, a standardized sham protocol is used where the current ramped up and then down breifly in the beginning and end of each session to simulate active stimulation.
Sponsors
Flow Neuroscience AB
University of Texas
University of East London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Participants and investigators are unaware of what stimulation (active or sham) the device delivers.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Be ≥18 years. * Have a diagnosis of Unipolar MDD with a current depressive episode as defined by the diagnostic criteria in the Diagnostic and statistical manual of mental disorders - 5th edition (DSM-V) * Have a Hamilton Depression Rating Score (HDRS-17) of ≥ 16. * Have PHQ-9 of ≥10.Montgomery-Åsberg Depression Rating Scale Self-Report (MADRS-s) of ≥ 20. * For 6 weeks prior to enrollment, are either: not taking antidepressant medication or: are taking a stable antidepressant regimen with a stable medication source and agree to continue the same regimen throughout study participation * If in psychotherapy, have maintained stable psychotherapy for at least 6 weeks prior to enrollment. * Have access to a stable internet connection through which the treatment will be received. * Have access to a smartphone or other device running Android 5.0+ or iPhone Operating System (iOS) 12+ (e.g., reasonably new iPhone/iPad or Android phone), used to using the device in their everyday life, and can capably use the study application on the device, as determined by the investigator. * Are currently living in England/Wales (UK) or Texas (US). * Subject is currently under the care of a psychiatrist or a primary care physician, agrees to be evaluated at regular intervals by a psychiatrist or primary care physician for the duration of study participation, and agrees to promptly inform the study staff of any change of psychiatric or mental health providers during study participation. * Subject agrees to allow any and all forms of communication between the investigators/study staff and any healthcare provider who currently provides and/or has provided service to the patient/subject within at least two years of study enrollment. * Subject agrees to provide the name and verifiable contact information (email and mailing addresses, mobile and land-line phone numbers, as applicable) of at least two persons ≥ age 18 (22 in the US) who reside within a 60-minute drive of the patient's residence and whom the research staff is at liberty to contact, as they deem necessary, for the duration of study participation. * Be able to give voluntary, written informed consent to participate and have signed an Informed Consent Form specific to this study. * Be willing and able to comply with all study procedures. * Subject agrees to meet all of the inclusion criteria throughout their participation in the study. Otherwise, the subject will be discontinued from the study. * Subject agrees to a Safety/Suicide Risk Management Protocol, which is intended to reduce the reduce the risk of suicide during study participation.
Exclusion criteria
* Are in a current state of mania, as determined by the YMRS or psychosis, as determined by the MINI. * Are diagnosed with vitamin or hormonal deficiencies that may mimic mood disorders, as determined by the investigator. * Are currently receiving any other interventional therapy for MDD other than a stable regimen of antidepressants or psychotherapy as defined in the inclusion criteria. * Considered to have treatment resistant depression as defined by inadequate clinical response to 2 or more trials of antidepressants at an adequate dose and duration. * Have a history of electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), cranial electrotherapy stimulation (CES), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), or other brain stimulation. * Patient answers Yes to Questions 4, 5 or 6 on the Columbia Suicide Severity Rating Scale (C-SSRS) Triage and Risk Identification Screener. * Any previous hospitilization for suicidal behavior. * Have chronic or current severe insomnia (\< 4 hours of sleep each night), or sleep apnea. * Have any structural lesion (e.g., any structural neurological condition, or more subcortical lesions than would be expected for age or have had a stroke that affects stimulated area or connected areas) or any other clinically significant abnormality that might affect safety, study participation, or confound interpretation of study results, as determined by the investigator. * Have any implant in the brain (e.g., DBS) or neurocranium, or any other active implantable medical device. * Have any neurocranial defect. * Have a history of epilepsy or seizures (including history of withdrawal / provoked seizures). * Have shrapnel or any ferromagnetic material in the head. * Have any disorder that would impair the ability to complete the study questionnaires. * Have been diagnosed with autism spectrum disorder. * Are actively abusing substances (\<1 week prior to enrollment). * Have a cognitive impairment (including dementia). * Have a history of mania or psychosis. * Are currently using any medications that affect cortical excitability (e.g., benzodiazepines, epileptics, etc.). * Are currently experiencing symptoms of withdrawal from alcohol or benzodiazepines. * Have been diagnosed with Parkinsonism or other movement disorder as determined by the investigator to interfere with treatment. * Have ever taken esketamine / ketamine for treatment of depression. * Have ever been admitted to hospital for depression. * Have been diagnosed with obsessive-compulsive disorder (OCD), bipolar type 1 or 2 disorder, an active primary anxiety disorder, PTSD, agoraphobia, panic or personality disorder. * Have a history of psychosurgery for depression. * Have any history of myocardial infarction, coronary artery bypass graft (CABG), coronary heart failure (CHF), or history of other cardiac issues. * Are currently experiencing or have a history of intractable migraines. * Are a chronic tobacco smoker, as defined by smoking \>100 cigarettes (including hand-rolled cigarettes, cigars, cigarillos, etc.) in their lifetime and has smoked every day in the last 7 days. * If female and of child-bearing potential, currently pregnant or breastfeeding or planning to become pregnant or breastfeed any time during the study. * Are currently a prisoner. * Are participating concurrently in another clinical investigation or have participated in a clinical investigation within the last 90 days or intend to participate in another clinical investigation during the study. * Have any medical condition or other circumstances, in the judgment of the investigator, that might interfere with the ability to complete follow-up visits and the self-reported MADRS-s in the app. * Have any condition which, in the judgment of the Investigator, would preclude adequate evaluation of the device's safety and performance.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HDRS-17 - Hamilton Depression Ratin Scale | 10 weeks | Comparison of mean score change based on HDRS-17 scores of the two arms at 10 weeks. Mean score change is calculated as change in score from baseline to week 10. HDRS-17 is a clinician rated diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Range of scores: 0 to 52. Higher scores represent greater severity of depressive symptoms. |
Countries
United Kingdom, United States
Participant flow
Recruitment details
Recruitment was from 12 May 2022 to 10 March 2023. Participants were recruited through the Flow Neuroscience website, email lists, and social media posts from throughout England and Wales (UK) and Texas (USA). From 17,951 individuals who completed an online pre-screen survey and 2,234 who had a pre-screen assessment via telephone, 368 individuals provided written informed consent and were assessed for eligibility via video conference.
Pre-assignment details
368 participants signed a consent form and were assessed for eligibility. 194 participants were excluded at the eligibility screening phase. 174 participants who had signed the consent form were enrolled onto the trial and were randomized (87 active, 87 sham). One participant in the sham group did not receive any treatment and was excluded from the modified intention-to-treat analysis (n=173).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 174 Participants |
| Age, Continuous | 37.09 years STANDARD_DEVIATION 11.14 |
| HDRS-17 - Hamilton Depression Rating Scale | 19.18 Total score STANDARD_DEVIATION 2.83 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 145 Participants |
| Sex: Female, Male Female | 54 Participants |
| Sex: Female, Male Male | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 87 | 0 / 86 |
| other Total, other adverse events | 0 / 87 | 0 / 86 |
| serious Total, serious adverse events | 1 / 87 | 0 / 86 |
Outcome results
None listed