Clinical trial NCT03191058: Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression
Official title: Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST - MST)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Depression
Unipolar Depression
Treatment Resistant Depression
Keywords: Depression
Unipolar Depression
Treatment Resistant Depression
Magnetic Seizure Therapy
Suicidal Ideation
Electroconvulsive Therapy
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
name: Centre for Addiction and Mental Health
name: University of California, San Diego
First posted: 2017-06-19
Enrollment: 219
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study is a randomized, double blind, parallel--group clinical trial with two treatment arms conducted both at the University of Texas Southwestern in Dallas, Texas and at the Temerty Centre for Therapeutic Brain Intervention based at CAMH in Toronto, Canada. Both sites aim to recruit 130 participants each.
Primary purpose: TREATMENT

Brief summary: This trial aims to assess the efficacy and tolerability of Magnetic Seizure Therapy (MST) as an alternative to electroconvulsive therapy (ECT) for depression. Even with multiple medication trials, 30 - 40% of patients will experience a pharmacologically resistant form of illness. The ineffectiveness of current treatments for major depressive disorder (MDD) coupled with the economic burden associated with the disorder engenders a need for novel therapeutic interventions that can provide greater response and remission rates.

Detailed description: The study will involve a randomized, double blind, non-inferiority clinical trial with two treatment arms conducted in two international academic medical centers (the Centre for Addiction and Mental Health in Toronto, Canada and UT Southwestern in Dallas, Texas). The investigators are pursuing a non-inferiority clinical trial in an effort to compare MST - a new treatment for TRD - to RUL-UB-ECT. Treatment will be administered two to three days per week. Depression symptoms will be assessed with the 24-item Hamilton Depression Rating Scale (HRSD-24) and suicidality will be assessed with the Scale for Suicidal Ideation (SSI). Remission will be defined as HRSD-24 \< or = 10 and a \> 60% decrease in scores from baseline on two consecutive ratings. Once a participant reaches remission, a second rating to confirm remission will be conducted immediately before their next scheduled treatment. If remission is confirmed, they will then be considered a completer of the acute treatment course. Remission of suicidal ideation is defined as a score of 0 on the SSI. Therefore, there will be no specific minimum number of treatments that patients must receive to be classified as remitters. However, patients who do not meet remission criteria after 21 treatment sessions will be considered non-remitters and will cease treatment sessions. This maximum treatment number was chosen allowing for the possibility that MST may require more treatment sessions to achieve remission, similar to RUL-UB ECT. The blind will not be broken to participants until the completion of the entire study.

Eligibility criteria: Inclusion Criteria

Patients will be included if they:

1. are inpatients or outpatients;
2. are voluntary and competent to consent to treatment and research procedures according to ECT/MST attending psychiatrist;
3. have a MINI International Neuropsychiatric Interview diagnosis, Version 6 (MINI-6.0) diagnosis of non-psychotic MDD
4. are 18 years of age or older
5. have a baseline HRSD-24 score \> or = 21;
6. are considered to be appropriate to receive convulsive therapy as assessed by an ECT attending psychiatrist and a consultant anaesthesiologist
7. are agreeable to keeping their current antidepressant treatment constant during the intervention;
8. are likely able to adhere to the intervention schedule;
9. meet the MST safety criteria \[75\];
10. If a woman of child-bearing potential: is willing to provide a negative pregnancy test and agrees not to become pregnant during trial participation.

Exclusion Criteria

Patients will be excluded if they:

1. have a history of MINI diagnosis of substance dependence or abuse within the past three months;
2. have a concomitant major unstable medical illness;
3. are pregnant or intend to get pregnant during the study;
4. have a MINI diagnosis of any primary psychotic disorder
5. have a MINI diagnosis of obsessive compulsive disorder, or post-traumatic stress disorder deemed to be primary and causing more functional impairment than the depressive disorder
6. have probable dementia based on study investigator assessment;
7. have any significant neurological disorder or condition likely to be associated with increased intracranial pressure or a space occupying brain lesion, e.g., cerebral aneurysm;
8. present with a medical condition, a medication, or a laboratory abnormality that could cause a major depressive episode or significant cognitive impairment in the opinion of the investigator (e.g., hypothyroidism with low TSH, rheumatoid arthritis requiring high dose prednisone, or Cushing's disease);
9. 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;
10. require a benzodiazepine with a dose \> lorazepam 2 mg/day or equivalent or any anticonvulsant due to the potential of these medications to limit the efficacy of both MST and ECT;
11. are unable to communicate in English fluently enough to complete the neuropsychological tests;
12. have a non-correctable clinically significant sensory impairment (i.e., cannot hear or see well enough to complete the neuropsychological tests).

Primary outcomes:
measure: Improvement in symptom severity of depression as measured by the Hamilton Rating Scale for Depression - 24 (HRSD-24)
timeFrame: 7 weeks
measure: Cognitive adverse effects as indexed by the Autobiographical Memory Test (AMT)
timeFrame: 7 weeks
Secondary outcomes:
measure: Improvement in symptom severity of Suicidal Ideation as measured by the Scale for Suicidal Ideation (SSI)
timeFrame: 7 weeks
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Toronto
country: Canada
facility: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health
state: Ontario
Study officials:
affiliation: Centre for Addiction and Mental Health
name: Daniel Blumberger, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Daskalakis ZJ, McClintock SM, Hadas I, Kallioniemi E, Zomorrodi R, Throop A, Palmer L, Farzan F, Thorpe KE, Tamminga C, Blumberger DM. Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST-MST): protocol for identification of novel biomarkers via neurophysiology. Trials. 2021 Dec 11;22(1):906. doi: 10.1186/s13063-021-05873-7.
citation: Daskalakis ZJ, Tamminga C, Throop A, Palmer L, Dimitrova J, Farzan F, Thorpe KE, McClintock SM, Blumberger DM. Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST-MST): study protocol for a randomized non-inferiority trial of magnetic seizure therapy versus electroconvulsive therapy. Trials. 2021 Nov 8;22(1):786. doi: 10.1186/s13063-021-05730-7.
citation: Regenold WT, Deng ZD, Lisanby SH. Noninvasive neuromodulation of the prefrontal cortex in mental health disorders. Neuropsychopharmacology. 2022 Jan;47(1):361-372. doi: 10.1038/s41386-021-01094-3. Epub 2021 Jul 16.
citation: Jiang J, Zhang C, Li C, Chen Z, Cao X, Wang H, Li W, Wang J. Magnetic seizure therapy for treatment-resistant depression. Cochrane Database Syst Rev. 2021 Jun 16;6(6):CD013528. doi: 10.1002/14651858.CD013528.pub2.