Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST-MST)

• ClinicalTrials.gov Identifier: NCT03191058
• Recruitment Status: Recruiting
• First Posted: June 19, 2017
• Last Update Posted: August 31, 2022
• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: National Institute of Mental Health (NIMH); Centre for Addiction and Mental Health; University of California, San Diego
• Information provided by (Responsible Party): Carol A. Tamminga, University of Texas Southwestern Medical Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Depression; Unipolar Depression; Treatment Resistant Depression	Device: Magnetic Seizure Therapy; Device: Electroconvulsive Therapy	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 260 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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.
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Masking Description: Participants will be randomized into the study using a permuted block method with a random number generator. The study statistician will prepare the randomization scheme. The block size will be varying and study personnel will be blinded to the randomization block size.
• Primary Purpose: Treatment
• Official Title: Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST - MST)
• Actual Study Start Date: June 26, 2018
• Estimated Primary Completion Date: July 2024
• Estimated Study Completion Date: July 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Magnetic Seizure Therapy (MST); MST treatments will be administered using the MagPro MST with Cool TwinCoil.	Device: Magnetic Seizure Therapy; MST treatment will be administered using the MagPro MST with a Cool TwinCoil over the frontal cortex in the midline position using 100 Hz stimulation. The MST determination of seizure threshold will be done using 100% machine output applied at 100 Hz at progressively escalating train durations, commencing at 2 seconds and increasing by 2 seconds with each subsequent stimulation until an adequate seizure is produced. During subsequent sessions, one stimulation will be delivered using a train duration that is 4 seconds longer than the train duration at threshold (with a maximum train duration of 10 seconds). This will be performed under the effect of anesthesia. The treatment procedure is approximately 10 minutes, followed by a recovery period of approximately 30 minutes.; Other Name: MST
Active Comparator: Electroconvulsive Therapy (ECT); ECT treatments will be administered using the MECTA spECTrum 5000Q or the MECTA Sigma devices.	Device: Electroconvulsive Therapy; In the ECT arm treatment, the MECTA spectrum 5000Q or the MECTA Sigma devices will be used, which are FDA approved devices used for providing standard-of-care clinical ECT treatments. The ECT determination of seizure threshold and the adjustment of energy at subsequent sessions will be based on a standard published protocol. All participants will receive RUL-UB ECT at six times the seizure threshold under the effect of anesthesia. The treatment procedure is approximately 10 minutes, followed by a recovery period of approximately 30 minutes; Other Name: ECT

Outcome Measures

Primary Outcome Measures :

1. Improvement in symptom severity of depression as measured by the Hamilton Rating Scale for Depression - 24 (HRSD-24) [ Time Frame: 7 weeks ]

   Hamilton Rating Scale for Depression (24-item version):

   • This scale is used to quantify the severity of symptoms of depression
   • Scale range: 0-76 (total score)
   • Lower scores indicate lower severity of depressive symptoms (i.e., better outcome)
   • Higher scores indicate higher severity of depressive symptoms (i.e., worse outcome)
2. Cognitive adverse effects as indexed by the Autobiographical Memory Test (AMT) [ Time Frame: 7 weeks ]

   Autobiographical Memory Test:

   -Interviewer-rated measure with 10 items that indexes autobiographical memory recall and specificity.

Secondary Outcome Measures :

1. Improvement in symptom severity of Suicidal Ideation as measured by the Scale for Suicidal Ideation (SSI) [ Time Frame: 7 weeks ]

   Scale for Suicidal Ideation:

   • This scale is used to assess the presence or absence of suicidal ideation and the degree of severity of suicidal ideas
   • Scale range: 0 - 38 (total score)
   • Lower scores indicate lower severity of suicidal ideation (i.e., better outcome)
   • Higher scores indicate higher severity of suicidal ideation (i.e., worse outcome)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Contacts

Contact: Daniel Blumberger, MD; 416-535-8501 ext 33662; Daniel.Blumberger@camh.ca

Contact: Hannah Taalman, MSc; 416-535-8501 ext 30990; Hannah.taalman@camh.ca

Locations

United States, California

University of California San Diego; Not yet recruiting

San Diego, California, United States, 92127

Contact: Z. Jeff Daskalakis, MD PhD 858-207-0938 IPtrials@health.ucsd.edu

Contact: Danielle Mitgang 858 207 0938 IPtrials@health.ucsd.edu

Principal Investigator: Z. Jeff Daskalakis, MD PhD

United States, Texas

University of Texas Southwestern Medical Center; Recruiting

Dallas, Texas, United States, 75390-9127

Contact: Carol A Tamminga, MD 214-648-2806 Carol.Tamminga@UTSouthwestern.edu

Contact: Hila Abush Segev, PhD 214-648-0401 Hila.Abushsegev@UTSouthwestern.edu

Principal Investigator: Carol A Tamminga, MD

Canada, Ontario

Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health; Recruiting

Toronto, Ontario, Canada, M6J 1H4

Contact: Daniel Blumberger, MD (416) 535-8501 ext 33662 Daniel.Blumberger@camh.ca

Contact: Dov Millstone, MPH (416) 535-8501 ext 36434 Dov.Millstone@camh.ca

Principal Investigator: Daniel Blumberger, MD

Sponsors and Collaborators

University of Texas Southwestern Medical Center

National Institute of Mental Health (NIMH)

Centre for Addiction and Mental Health

University of California, San Diego

Investigators

• Principal Investigator: Daniel Blumberger, MD; Centre for Addiction and Mental Health

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

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.

• Responsible Party: Carol A. Tamminga, Professor and Chairperson, Department of Psychiatry, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT03191058
• Other Study ID Numbers: CREST-MST; 1R01MH112815-01 ( U.S. NIH Grant/Contract )
• First Posted: June 19, 2017
• Last Update Posted: August 31, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by Carol A. Tamminga, University of Texas Southwestern Medical Center:

Depression; Unipolar Depression; Treatment Resistant Depression; Magnetic Seizure Therapy; Suicidal Ideation; Electroconvulsive Therapy

Additional relevant MeSH terms:

Seizures; Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant; Behavioral Symptoms; Mood Disorders; Mental Disorders; Neurologic Manifestations; Nervous System Diseases