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Bipolar Disorder (BD)DEEPPNCT05177146

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

A study testing Intravenous Ketamine (IV) in people with Bipolar Disorder (BD) and Suicidality, run by Centre for Addiction and Mental Health at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 24 to 65 years
Conditions the study is for
Bipolar Disorder (BD), Suicidality
What is being tested?
Intravenous Ketamine (IV)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
1 siteCanada
Study dates
4 May 2022to 10 Jan 2025
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 24 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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
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  • 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
  • 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

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • Centre for Addiction and Mental Health

    Toronto, Ontario, M5T 1R8

Other trials in Canada

About this study

Official title: Neural Correlates of Anti-suiciDal rEsponse to kEtamine in Treatment Resistant biPolar dePression (DEEPP-Study)

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.

Read the 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. Sub-anesthetic doses of ketamine administered intravenously (IV) have shown to produce rapid antidepressant and ant-suicidal effects. Despite this important clinical finding, our understanding of ketamine's neurophysiological mechanism of action for suicidality remains limited. This clinical trial is an open label pilot study that aims to address this limitation by studying the effects of IV ketamine on patients with bipolar depression who are currently experiencing suicidal thoughts. Using a combination of Transcranial Magnetic Stimulation (TMS) neurophysiological tools with electromyography (EMG) and electroencephalography (EEG), this trial aims to explore ketamine's action on NMDA neurotransmission to understand ketamine's anti-suicidal effects. Investigating the impact of ketamine on cortical excitation, cortical inhibition, and resting-state cortical oscillation could provide insight into the role of NMDA receptors in cortical physiology and determine potential predictors of clinical response for suicidality in bipolar depression.

Objective 1: To examine the effect of a series of therapeutic IV ketamine 40-min infusions on neurophysiological markers linked with cortical excitation and inhibition (as indexed via TMS-EMG and TMS-EEG, as a proxy of NMDA-receptor activity in the cortex)

Hypothesis 1: Ketamine will increase intracortical facilitation - a neurophysiological measure of NMDA neurotransmission

Objective 2: To examine the effect of ketamine IV 40-min infusions in sub-anesthetic doses on acute suicidality in patients with BD

Hypothesis 2: Ketamine infusions will result in improvement of suicidality in BD

Objective 3: To examine the safety and tolerability of ketamine IV 40-min infusions in sub-anesthetic doses and its effect on depressive symptoms in patients with BD

Hypothesis 3:

  1. Ketamine infusions will be safe and well tolerated
  2. Ketamine infusions will result in improvement of depressive mood symptoms in BD

Objective 4: To examine the effect of ketamine IV 40-min infusions in sub-anesthetic on additional neurophysiological measures and on changes in quality of life measures

Hypothesis 4:

  1. Ketamine will decrease cortical inhibitory measures as indexed by (SICI) paradigms
  2. Ketamine will increase cortical excitation measures as indexed by TMS-evoked potential waveform amplitude
  3. Ketamine infusions will result in improvement in quality of life measures
Being tested
Intravenous Ketamine (IV)
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)
Medical subject headings
Bipolar Disorder, Suicidal Ideation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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.

Study groups in NCT05177146
Study groupRoleWhat they receive
Intravenous Ketamine (IV)ExperimentalNot described
Receives: Drug: Intravenous Ketamine (IV)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: 1 month

  2. 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).

    Measured: 1 month

Secondary outcomes (2)

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

    Scale for Suicide Ideation (SSI); 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)

    Measured: 2 months

  2. 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)

    Measured: 2 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Jan 2022
  2. Study start4 May 2022
  3. Primary completion10 Jan 2025
  4. Study completion10 Jan 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Open label pilot study
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05177146
Sponsor's protocol ID
179-2020
Acronym
DEEPP
Status last verified
Jan 2025
First submitted
15 Dec 2021
Last updated
6 Feb 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 36573651

Questions about this trial

What is this clinical trial studying?

A study testing Intravenous Ketamine (IV) in people with Bipolar Disorder (BD) and Suicidality, run by Centre for Addiction and Mental Health at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Impact of a series of therapeutic IV Ketamine 40-min infusions on cortical excitation as measured by intracortical facilitation (ICF) (time frame: 1 month). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05177146, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2025.

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