Temporal Interference and Depression (TI)

This is an interventional treatment trial for Major Depressive Disorder Read More

Inclusion Criteria - Patients will be included if they:

1. provide written informed consent before initiation of any study-related procedures
2. are outpatients
3. meet the DSM-5 criteria for major depressive disorder (MDD) with a current major depressive episode (MDE) without psychotic features as confirmed at Screening by the Mini International Neuropsychiatric Interview (MINI)
4. are male or female, 18 to 65 years of age (inclusive) at screening
5. have a Montgomery-Åsberg Depression Rating Scale (MADRS) total score of ≥ 20 (moderate to severe depression) at screening
6. have had no increase or initiation of any psychotropic medication in the 4 weeks prior to screening
7. able to adhere to the treatment schedule
8. pass the TI adult safety screening questionnaire
9. have normal thyroid functioning based on pre-study blood work
10. are able to understand and comply with the requirements of the study, as judged by the investigator(s)

Exclusion Criteria - Patients will be excluded if they:

1. have an acute alcohol or substance use disorder, withdrawal symptoms requiring detoxification, or went through detoxification treatment (inpatient or outpatient) within 3 months before Screening as obtained from MINI, Module I (Alcohol Use Disorder) and Module J (Substance Use Disorder, Non-Alcohol) assessed at Screening
2. have a concomitant major unstable medical illness, Active hepatitis B virus (HBV), hepatitis C virus (HPC), human immunodeficiency virus (HIV), active COVID-19 infection, cardiac pacemaker or implanted medication pump as per medical history provided by the participant
3. have active suicidal intent, confirmed by a 'Yes' response to Question B3 AND either Question B10 or B11 obtained from the MINI Suicidality, Module B (Suicidality) assessed at Screening
4. have suicidal ideation or behaviour caused primarily by another non-MDD condition, as obtained from MINI, Module Z (Suicidality Disorders Classification Interview) assessed at Screening
5. have a current clinical diagnosis of autism, dementia, or intellectual disability
6. take medications prohibited by the protocol. Medications will be reviewed by the responsible MD and decisions about inclusion will be made based on a predetermined list of contraindicated medications.
7. are pregnant or lactating
8. have any prior or current Mini-International Neuropsychiatric Interview (MINI) diagnosis of bipolar I or II disorder, MDD with psychotic features, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms as obtained from MINI, Module C (Manic and Hypomanic Episodes) and Module K (Psychotic Disorders and Mood Disorders with Psychotic Features) assessed at Screening
9. have any prior or current Mini-International Neuropsychiatric Interview (MINI) diagnosis of obsessive-compulsive disorder, post-traumatic stress disorder (current or within the last year), anxiety disorder (generalized anxiety disorder, social anxiety disorder, panic disorder), or dysthymia, assessed by a study investigator to be primary and causing greater impairment than MDD
10. have a diagnosis of any personality disorder, and assessed by a study investigator to be primary and causing greater impairment than MDD
11. have failed a course of ECT or intravenous ketamine therapy in the current episode or previous episode
12. have received TI for any previous indication due to the potential compromise of subject blinding
13. have any significant neurological disorder or insult including, but not limited to: any condition likely to be associated with increased intracranial pressure, space-occupying brain lesion, any history of seizure except those therapeutically induced by ECT or a febrile seizure of infancy, cerebral aneurysm, Parkinson's disease, Huntington's chorea, multiple sclerosis, significant head trauma with loss of consciousness for greater than 5 minutes, current history of poorly controlled migraines including chronic medication for migraine prevention
14. have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed
15. if participating in psychotherapy, must have been in stable treatment for at least 3 months prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions, or the therapeutic focus over the duration of the study
16. have a clinically significant laboratory abnormality, in the opinion of one of the principal investigators or study physicians
17. currently take medications that potentially limit the TI efficacy
18. have a non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with an interview)
19. have a clinical finding that is unstable or that, in the opinion of the investigator(s), would be negatively affected by the study medication or that would affect the study medication (e.g., diabetes mellitus, hypertension, unstable angina)
20. have uncorrected hypothyroidism or hyperthyroidism. Subjects needing a thyroid hormone supplement to treat hypothyroidism must have been on a stable dose of the medication for 30 days prior to enrolment.
21. have any other condition that, in the opinion of the investigator(s), would adversely affect the subject's ability to complete the study or its measure
22. wear a hairstyle or headdress that prevents electrode contact with the scalp or would interfere with the stimulation (e.g., thick braids, hair weave, afro, wig)
23. have any contraindications for receiving TI or undergoing MRI scans (e.g., hip circumference <180 cm or metal in the body)