Clinical trial NCT03113968: ELEKT-D: Electroconvulsive Therapy (ECT) vs. Ketamine in Patients With Treatment Resistant Depression (TRD)
Official title: ELEKT-D: Electroconvulsive Therapy (ECT) vs. Ketamine in Patients With Treatment Resistant Depression (TRD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Treatment Resistant Depression
Electroconvulsive Therapy
ECT
Ketamine
Psychiatric Disorder
Depression
Major Depressive Disorder
Major Depressive Episode
Unipolar Depression
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
First posted: 2017-04-14
Enrollment: 403
Sex: ALL
Minimum age (years): 21
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: unblinded prospective randomized open-label
Primary purpose: TREATMENT

Brief summary: The goal of the study is to conduct a comparative randomized trial of electroconvulsive therapy (ECT) vs. ketamine for patients with treatment resistant depression (TRD) in a real world setting with patient reported outcomes as primary and secondary outcome measures.

Detailed description: Patients with treatment resistant depression who meet all inclusion criteria and do not meet any exclusion criteria will be randomized to either electroconvulsive therapy (ECT) three times per week or ketamine infusion two times per week. Patients will answer questionnaires about their symptoms prior to treatments. The acute treatment phase of the study will last three to five weeks. Depending on response to treatment, some patients will be followed for an additional six months.

Eligibility criteria: Inclusion Criteria:

1. Written informed consent before any study related procedures are performed
2. Inpatients or outpatients referred by their providers for ECT treatment and eligible for ECT treatment
3. Males/females at least 21 years of age but no older than 75 years of age
4. Meet DSM-5 criteria for Major Depressive Episode as determined by both:

   A. a clinician's diagnostic evaluation and B. confirmed with the MINI International Neuropsychiatric Interview (MINI 7.0.2)
5. A current depressive episode that has lasted a minimum of 4 weeks
6. Meet all of the following criteria on symptom rating scales at screening:

   A. Montgomery Asberg Depression Rating Scale (MADRS) score \>20 B. Young Mania Rating Scale (YMRS) of ≤ 5 C. Montreal Cognitive Assessment (MoCA) of ≥18
7. Have had ≥2 adequate trials of antidepressants or augmentation strategies during their lifetime. An adequate trial is defined as 4 weeks of medication at the minimum FDA approved dose. This will be equal to a trial rating of 3 or more.
8. In the opinion of the investigator, the patient is willing and able to comply with scheduled visits, treatment plan, and other trial procedures for the duration of the study

Exclusion Criteria:

1. Meet DSM-5 criteria for bipolar disorder, schizophrenia, schizophreniform disorder, schizoaffective disorder, mental retardation, or pervasive developmental disorder
2. Meets any exclusion criteria for ECT or ketamine treatment as described in the clinical guidelines or according to investigator judgment
3. The patient is pregnant or breast feeding
4. The patient has a severe medical illness or severe neurological disorder
5. The patient has a known ketamine allergy or is taking a medication that may interact with ketamine
6. Diagnosis of major depressive disorder with psychotic features during the current depressive episode
7. Unable to give informed consent
8. Was previously enrolled/randomized into the trial

Primary outcomes:
measure: Number of Participants With Treatment Responses Based on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report Scale (QIDS-SR-16)
timeFrame: Acute Study Phase (Baseline Visit to End of Treatment Visit) - approximately 3-5 weeks
Secondary outcomes:
measure: Number of Participants With Treatment Responses Based on the Montgomery-Åsberg Rating Scale (MADRS)
timeFrame: Acute Study Phase (Baseline Visit to End of Treatment Visit) - approximately 3-5 weeks
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: New York
country: United States
facility: Mount Sinai
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
affiliation: The Cleveland Clinic
name: Amit Anand, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nemeroff CB. Prevalence and management of treatment-resistant depression. J Clin Psychiatry. 2007;68 Suppl 8:17-25.
citation: Kellner CH, Greenberg RM, Murrough JW, Bryson EO, Briggs MC, Pasculli RM. ECT in treatment-resistant depression. Am J Psychiatry. 2012 Dec;169(12):1238-44. doi: 10.1176/appi.ajp.2012.12050648.
citation: Lisanby SH. Electroconvulsive therapy for depression. N Engl J Med. 2007 Nov 8;357(19):1939-45. doi: 10.1056/NEJMct075234. No abstract available.
citation: Newport DJ, Carpenter LL, McDonald WM, Potash JB, Tohen M, Nemeroff CB; APA Council of Research Task Force on Novel Biomarkers and Treatments. Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression. Am J Psychiatry. 2015 Oct;172(10):950-66. doi: 10.1176/appi.ajp.2015.15040465.
citation: Sanacora G, Heimer H, Hartman D, Mathew SJ, Frye M, Nemeroff C, Robinson Beale R. Balancing the Promise and Risks of Ketamine Treatment for Mood Disorders. Neuropsychopharmacology. 2017 May;42(6):1179-1181. doi: 10.1038/npp.2016.193. Epub 2016 Sep 19. No abstract available.
citation: Mathew SJ, Wilkinson ST, Altinay M, Asghar-Ali A, Chang LC, Collins KA, Dale RM, Hu B, Krishnan K, Kellner CH, Malone DA, Murrough JW, Ostroff RB, Sanacora G, Shao M, Anand A. ELEctroconvulsive therapy (ECT) vs. Ketamine in patients with Treatment-resistant Depression: The ELEKT-D study protocol. Contemp Clin Trials. 2019 Feb;77:19-26. doi: 10.1016/j.cct.2018.12.009. Epub 2018 Dec 17.