Intranasal Ketamine in Ultra-REsistant Depression (SURE-ECT Non Responders)

NCT05137938 | Completed

• 1 other identifier: 095-2019
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Despite the known efficacy of pharmacotherapy (i.e. antidepressants) and psychotherapeutic interventions in treating depressive disorders, research evidence suggests that 20% to 40% of patients with major depressive disorder (MDD) do not respond adequately to such treatments. These patients are diagnosed with Treatment-Resistant Depression (TRD), and are sometimes treated with convulsive therapy. However, about 10-30% of TRD patients do not respond to convulsive therapy, and are thus diagnosed with Ultra-Resistant Depression (URD). Using an open label pilot study involving subjects, this trial aims to assess the safety, tolerability, and clinical effects of intranasal ketamine (IN) treatment in patients who do not respond to convulsive therapy. Intranasal ketamine (IN) treatment approach has shown promising therapeutic outcomes for patients with TRD, but has not yet been studied on patients with URD.

Conditions

Depression

Keywords

Convulsive therapy; Open-label trial; Pilot study; Treatment-resistant depression (TRD); Ketamine; Intranasal drug delivery (IN); N-methyl-d-aspartate (NMDA); Receptor antagonist; Transcranial magnetic stimulation (TMS); Electromyography (EMG); Electroencephalography (EEG); Intracortical facilitation (ICF); Short-interval cortical inhibition (SICI); Electroconvulsive Therapy (ECT)

Outcome Measures

Primary Outcomes (1)

• Change in symptom severity of depression as measured by the Hamilton Rating Scale for Depression - 24

  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 months

Secondary Outcomes (7)

• Change in symptom severity of Suicidal Ideation as measured by by the Scale of Suicide Ideation (SSI)

  2 months

• Safety and tolerability as assessed by changes in Blood Pressure (BP)

  1 month

• Safety and tolerability as assessed by changes in Heart Rate (BPM)

  1 month

• Safety and tolerability as assessed by changes in O2 Saturation

  1 month

• Safety and Tolerability of IN Ketamine as assessed by monitoring of adverse events

  2 months

Other Outcomes (1)

• Change in quality of life measures as assessed by the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0)

  1 month

Study Arms (1)

Intranasal Ketamine (IN)

EXPERIMENTAL

Ketamine will be administered intranasally (IN) using an atomizer (MAD300 by Teleflex, North Carolina, USA).

Drug: Intranasal Ketamine (IN)

Interventions

Intranasal Ketamine (IN) DRUG

A sterile form of ketamine will be administered intranasally twice weekly for four weeks. Dosing schedule will be determined based on patient's weight using a specialized formula. Patients will be started at the lowest dose during the first treatment session. Dose will be titrated further to therapeutic dose in the following sessions. The dose will be adjusted if patients do not tolerate full therapeutic doses. After receiving the second treatment of each week, participants will be seen by a study physician to determine dosing for the following week. Patients will be monitored by trained personnel for the full duration of the 2 hour supervision period. Vital signs and physical symptoms will be monitored consistently and measurements taken every 30 minutes. Appropriate medications will be provided to manage treatment-related side effects and any adverse events. Labetalol will be used in the management of treatment-related transient hypertension as needed.

Intranasal Ketamine (IN)

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals with a diagnosis of non-psychotic MDD as confirmed by the Mini-International Neuropsychiatric Interview (MINI)
• Individuals meeting criteria for Ultra Resistant Major Depressive Disorder (URD) in current episode
• URD is defined as:
• those who received at least eight convulsive therapy treatment sessions and did not respond, or
• those who were not able to tolerate convulsive therapy
• Individuals scoring 14 and above on the Hamilton Rating Scale for Depression-24 Items (HRSD-24)
• Individuals capable to provide consent who are receiving care as outpatients

You may not qualify if:

• Individuals with history of substance use disorder (i.e. dependence or abuse) within the past month; and lifetime history of ketamine substance use disorder as confirmed by the MINI
• Concomitant major unstable medical illness such as poorly controlled high blood pressure or patients diagnosed with enlarged prostate or reporting any other urinary related issues
• Pregnancy or the intention to become pregnant and breastfeeding during the study as confirmed by self-report. Female participants of reproductive potential must be willing to use a medically acceptable method of birth control which include highly effective (e.g. approved hormonal contraceptives, intrauterine device, tubal ligation) or double barrier (e.g. male condom with diaphragm, male condom with cervical cap) methods of contraception or abstinence if that is the usual and preferred lifestyle of the participant
• Presence of cardiac decompensation/heart failure v)
• Diagnosis of any primary psychotic disorder, bipolar disorder, obsessive-compulsive disorder, or post-traumatic stress disorder (current) as confirmed by the MINI
• Diagnosis of severe personality disorder as assessed during the initial consultation with a physician at the Temerty Centre prior to study entry
• Any significant neurological disorder (e.g., a space occupying brain lesion, a history of stroke, a cerebral aneurysm, a seizure disorder, Parkinson's disease, Huntington's chorea, multiple sclerosis) as assessed through medical history review during the initial consultation with a physician at the Temerty Centre prior to study entry
• Individuals presenting 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
• Individuals requiring a benzodiazepine with a dose equivalent to lorazepam 2 mg/day or higher; being on any anticonvulsant(e.g. Lamotrigine) and/or opioid medication due to the potential of these medications to limit the efficacy of ketamine
• Individuals unable to communicate in spoken and written English fluently enough to complete the required study assessments due to a language barrier or a non-correctable clinically significant sensory impairment (i.e., cannot hear or see well enough to complete clinical assessments)
• Individuals with cognitive or physical impairment which may potentially interfere with IN ketamine administration and subject's ability to stay in the same place for a 2-hr monitoring supervision as assessed through medical history review during the initial consultation with a physician at the Temerty Centre prior to study entry
• Any intracranial implant (e.g., aneurysm clips, shunts, cochlear implants) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed given that we will be using TMS-EMG/EEG
• Those unable to secure escort to accompany them back home after ketamine sessions will also be excluded from this study
• Any known allergy to the study medication or any component/ingredient of the ketamine preparation

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M5T 1R8, Canada

Location

Related Publications (1)

• Knyahnytska Y, Zomorrodi R, Kaster T, Voineskos D, Trevizol A, Blumberger D. The Safety, Clinical, and Neurophysiological Effects of Intranasal Ketamine in Patients Who Do Not Respond to Electroconvulsive Therapy: Protocol for a Pilot, Open-Label Clinical Trial. JMIR Res Protoc. 2022 Jan 17;11(1):e30163. doi: 10.2196/30163.

  PMID: 34882570 DERIVED

MeSH Terms

Conditions

Depression; Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Yuliya Knyahnytska, MD, PhD

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open label pilot study

Study Record Dates

• First Submitted: November 2, 2021
• First Posted: November 30, 2021
• Study Start: October 25, 2021
• Primary Completion: July 24, 2023
• Study Completion: July 24, 2023
• Last Updated: August 14, 2023

Record last verified: 2023-08

Locations

CA (1)