Neural Correlates of Ketamine's Anti-suicidal Effects in Bipolar Depression

NCT05177146 | Completed

• 1 other identifier: 179-2020
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Bipolar disorder is characterized by manic episodes and episodes of extreme depressive feelings, also known as bipolar depression (BD). Although clinical data does not suggest significant differences in the severity of depressive symptoms between bipolar and unipolar depression, patients with BD are found to be more likely to experience suicidal ideation and suicide attempts. Innovative treatments for suicidality in patients with BD are needed to address tolerability and slow effect limitations of current interventions. Using an open label pilot study, this trial aims to examine the effect of Intravenous (IV) ketamine treatment on acute suicidality in patients with BD. Moreover, the study aims to explore the neurophysiological mechanisms of ketamine's action directly from the cortex in patients with BD, in order to understand the biological mechanism underlying ketamine's therapeutic action.

Conditions

Bipolar Disorder (BD); Suicidality

Keywords

Transcranial magnetic stimulation (TMS); Open-label trial; Pilot study; Ketamine; Intravenous drug delivery (IV); N-methyl-d-aspartate (NMDA); Receptor antagonist; Electromyography (EMG); Electroencephalography (EEG); Intra-cortical facilitation (ICF); Short-interval cortical inhibition (SICI)

Outcome Measures

Primary Outcomes (2)

• Impact of a series of therapeutic IV Ketamine 40-min infusions on cortical excitation as measured by intracortical facilitation (ICF)

  Assessed through administration of neurophysiological paradigms using Transcranial Magnetic Stimulation (TMS) paired with electromyography (EMG) and electroencephalography (EEG).

  1 month

• Impact of a series of therapeutic IV Ketamine 40-min infusions on cortical inhibition as measured by short-interval cortical inhibition (SICI)

  Assessed through administration of neurophysiological paradigms using Transcranial Magnetic Stimulation (TMS) paired with electromyography (EMG) and electroencephalography (EEG).

  1 month

Secondary Outcomes (2)

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

  2 months

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

  2 months

Other Outcomes (5)

• 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

Study Arms (1)

Intravenous Ketamine (IV)

EXPERIMENTAL

Drug: Intravenous Ketamine (IV)

Interventions

Intravenous Ketamine (IV) DRUG

A sterile form of ketamine hydrochloride will be administered over 40-min IV infusion twice per week on non-consecutive days for four weeks. Dosing schedule is determined based on patient's weight, clinical response and tolerability. First treatment session dose will be calculated based on 0.5 mg/kg. Further dose increase will be determined by the study physician. Dose increase will not exceed 0.8 mg/kg. Patients will be closely monitored by available trained personnel with MD being present on site for the full duration of the 2-h supervision period. Specifically, IV induction will be performed under the direct supervision of anesthesiologist or delegate and psychiatrist. Vital signs will be monitored every 30 minutes during the supervision period. Side effects will be managed by the medical team administering the treatment. If required, appropriate rescue medications will be provided depending on the nature of the adverse event.

Intravenous Ketamine (IV)

Eligibility Criteria

• Age: 24 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individual meeting DSM-IV diagnostic criteria for Bipolar Disorder, current depressive episode as confirmed by the Mini-International Neuropsychiatric Interview (MINI)
• Individuals capable to provide consent and able to communicate, read and write in English
• Individuals currently depressed defined as scoring 14 and above on the Hamilton Rating Scale for Depression-24 Items (HRSD-24)
• Individuals currently experiencing suicidal ideation as defined by a score of 9 or higher on the scale for suicide ideation (SSI)

You may not qualify if:

• Individuals with history of a DSM-IV 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
• Stage 2 hypertension defined as a systolic pressure of 140 mm Hg or higher or a diastolic pressure of 90 mm Hg or higher on three consecutive readings taken 5 minutes apart
• Results of liver function tests (ALT, AST) are three times or greater than the upper limit of normal readings
• 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, IUD, 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
• DSM-IV diagnosis of any primary psychotic disorder, bipolar disorder, obsessive-compulsive disorder, or post-traumatic stress disorder (current) as confirmed by the MINI
• Current episode meeting criteria for mania/hypomania or mixed episode as per DSM-IV criteria on the MINI or as determined by the study team
• 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

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. Neural Correlates of the DEEPP (Anti-suicidal Response to Ketamine in Treatment-Resistant Bipolar Depression) Study: Protocol for a Pilot, Open-Label Clinical Trial. JMIR Res Protoc. 2023 Jan 27;12:e41013. doi: 10.2196/41013.

  PMID: 36573651 DERIVED

MeSH Terms

Conditions

Bipolar Disorder; Suicidal Ideation

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Suicide; Self-Injurious Behavior; Behavioral Symptoms; Behavior

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: December 15, 2021
• First Posted: January 4, 2022
• Study Start: May 4, 2022
• Primary Completion: January 10, 2025
• Study Completion: January 10, 2025
• Last Updated: February 6, 2025

Record last verified: 2025-01

Locations

CA (1)