NCT05137938

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

Safety and Clinical Effects of Intranasal Ketamine in Ultra-REsistant Depression (SURE-ECT Non Responders). Pilot Study

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 25 (actual)
• Sponsor: Centre for Addiction and Mental Health · Academic / Other
• Sex: All
• Age: 21 Years – 65 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Ketamine is a fast-acting anesthetic that can have stimulant effects when taken at low doses. It acts as a non-competitive high-affinity N-methyl-d-aspartate (NMDA) receptor antagonist that stimulates synaptic glutamate release and blocks extra-synaptic NMDA receptors. This mechanism of action mediates excitatory synaptic transmission through the central nervous system and therefore results in robust antidepressant effects. Administering intravenous (IV) ketamine to patients with TRD has shown to produce rapid antidepressant effects. Nevertheless, delivering IV ketamine to patients can be challenging since it requires specialized expertise and equipment. A promising alternative that preserves IV ketamine's rapid onset of therapeutic action while minimizing inconvenience and discomfort is intranasal drug delivery (IN). This current proof-of-concept clinical trial is an open label pilot study on patients with treatment-resistant unipolar depression who did not respond to, or did not tolerate, an acute course of convulsive therapy. Using a combination of Transcranial Magnetic Stimulation (TMS) neurophysiological tools with electromyography (EMG) and electroencephalography (EEG), this trial also aims to explore biomarkers of ketamine's antidepressant effect by examining ketamine's action on NMDA neurotransmission. Investigating the impact of ketamine on cortical excitation and inhibition could provide insight into the role of NMDA receptors in cortical physiology, and therefore determine potential predictors of clinical response for depression. Objective 1: To test the safety and tolerability of IN ketamine in patients with URD who did not respond to/tolerate an acute course of convulsive therapy Hypothesis 1: IN ketamine will be safe and well tolerated in patients with URD Objective 2: To test the clinical effects of IN ketamine patients with URD who did not respond to/tolerate an acute course of convulsive therapy Hypothesis 2: IN ketamine will result in improvement in depressive symptoms, suicidal ideation, and quality of life measures (compared to scores from baseline) Objective 3: To investigate the impact of ketamine on cortical excitation via intracortical facilitation (ICF) and cortical inhibition via short-interval cortical inhibition (SICI) paradigms Hypothesis 3: IN ketamine will result in neurophysiological changes as measured by TMS-EMG and EEG

Conditions

• Depression

Interventions

Type	Name	Description
DRUG	Intranasal Ketamine (IN)	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.

Timeline

• Start date: 2021-10-25
• Primary completion: 2023-07-24
• Completion: 2023-07-24
• First posted: 2021-11-30
• Last updated: 2023-08-14

Locations

1 site across 1 country: Canada