NCT04205890

Brief Summary

The purpose of this study is to investigate the neuroanatomical effects of ketamine treatment on patients with treatment-resistant depression. The investigators will compare the neuroimaging of patients several days before and after injection in order to assess the more durable changes induced by ketamine. In addition, changes in perfusion will be analyzed, in addition to changes in neurovascular coupling, and functional connectivity that are correlated with psychiatric measures.

Trial Health

30
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started May 2020

Shorter than P25 for phase_1 depression

Geographic Reach
1 country

1 active site

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 16, 2019

Completed
4 days until next milestone

First Posted

Study publicly available on registry

December 20, 2019

Completed
4 months until next milestone

Study Start

First participant enrolled

May 2, 2020

Completed
26 days until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 28, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 28, 2020

Completed
Last Updated

June 1, 2020

Status Verified

May 1, 2020

Enrollment Period

26 days

First QC Date

December 16, 2019

Last Update Submit

May 28, 2020

Conditions

Depression

Keywords

intravenous ketaminetreatment-resistant depression

Outcome Measures

Primary Outcomes (6)

  • fMRI T1 baseline

    T1-data was collected as a sagittal MPRAGE sequence. T1 images are corrected for field biasing and then skull stripped and linearly registered to standard MNI space. Each patients' T1 image is segmented into 100 cortical and 15 subcortical areas using the Harvard-Oxford Cortical and Subcortical structural atlas. Mean volume is computed for each of these regions for each patient, which can be used for quantitative comparison.

    Images to be acquired 7 days prior to Ketamine intervention

  • fMRI T1 post-intervention comparison

    T1-data was collected as a sagittal MPRAGE sequence. T1 images are corrected for field biasing and then skull stripped and linearly registered to standard MNI space. Each patients' T1 image is segmented into 100 cortical and 15 subcortical areas using the Harvard-Oxford Cortical and Subcortical structural atlas. Mean volume is computed for each of these regions for each patient, which can be used for quantitative comparison.

    Images to be acquired at 2 days post-treatment

  • Arterial Spin Labeling (fMRI) baseline

    Pulsed Arterial Spin Labeling is collected as an echo planar sequence. ASL data is superimposed over the acquired T1-weighted brain image demonstrating a map of cerebral perfusion. Quantification to CBF values (milliliters of blood per 100g of tissue per minute) is implemented and voxel-based comparisons showing perfusion values relative to the acquired data range are used for quantification.

    Images to be acquired 7 days prior to Ketamine intervention

  • Arterial Spin Labeling (fMRI) post-intervention comparison

    Pulsed Arterial Spin Labeling is collected as an echo planar sequence. ASL data is superimposed over the acquired T1-weighted brain image demonstrating a map of cerebral perfusion. Quantification to CBF values (milliliters of blood per 100g of tissue per minute) is implemented and voxel-based comparisons showing perfusion values relative to the acquired data range are used for quantification.

    Images to be acquired at 2 days post-treatment

  • fMRI Resting Bold baseline

    The signal change measured in BOLD imaging comes from the brain oversupplying the region of activation with oxygen, leading to a focal decrease in deoxygenated hemoglobin. Processed BOLD imaging allows for visualization of hemodynamic response (HR) and neurovascular coupling (NVC) based on signal variability and distribution. These elements can be quantified and used for comparison.

    Images to be acquired 7 days prior to Ketamine intervention

  • fMRI Resting Bold post-intervention comparison

    The signal change measured in BOLD imaging comes from the brain oversupplying the region of activation with oxygen, leading to a focal decrease in deoxygenated hemoglobin. Processed BOLD imaging allows for visualization of hemodynamic response (HR) and neurovascular coupling (NVC) based on signal variability and distribution. These elements can be quantified and used for comparison.

    Images to be acquired at 2 days post-treatment

Secondary Outcomes (9)

  • Beck Depression Inventory

    7 days prior to treatment

  • Beck Depression Inventory

    Day of treatment

  • Beck Depression Inventory

    2 days after treatment

  • Beck Anxiety Inventory

    7 days prior to treatment

  • Beck Anxiety Inventory

    Day of treatment

  • +4 more secondary outcomes

Study Arms (1)

Ketamine

EXPERIMENTAL

The present study is designed as a prospective data analysis of patient response to the use of ketamine to treat treatment-resistant depression. For Phase I trail, 10 patients of any gender with an age range of 18 to 70 who have undergone the outlined procedure will be recruited for inclusion. A week before the scheduled ketamine treatment, the patients will have fMRI scans, including structural T1, Arterial Spin Labeling, and Resting BOLD. The scans take around 30 minutes at no charge to the patients. The ketamine will be injected per the doctor's orders to achieve a dissociative state; dosage will vary (see below) depending on every individual's unique treatment plan. The same scans will be taken two days after treatment.

Drug: Ketamine

Interventions

KetamineDRUG

The ketamine will be injected per the doctor's orders to achieve a dissociative state; dosage varies between 75mg - 1000mg depending on every individual's unique treatment plan.

Ketamine

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • In order for a subject to be considered for this study, the patient must have been diagnosed with treatment-resistant depression, meaning the patient failed three medications and has been suffering from moderate treatment-resistant depression for over 6 months, indicated by a Beck Depression Inventory score of 10 or above. The patient must have been prescribed ketamine as part of their treatment plan, completely independent of any research. The patient must be willing to comply with the study protocol.

You may not qualify if:

  • In order for a subject to be considered for this study, he/she may not have any of the following:
  • Advanced stages of any terminal illness or any active cancer that requires chemotherapy
  • Hepatic impairment
  • Significant cytopenia
  • Cardiovascular, cerebrovascular, and peripheral vascular arterial thrombosis
  • Women who are pregnant, may become pregnant, or are breastfeeding
  • Any counter indications to ketamine
  • Subjects unable to give informed consent or in vulnerable categories, such as prisoners

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Neurological Associates of West Los Angeles

Santa Monica, California, 90403, United States

Location

Related Publications (8)

  • Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000 Feb 15;47(4):351-4. doi: 10.1016/s0006-3223(99)00230-9.

    PMID: 10686270BACKGROUND

  • Deakin JF, Lees J, McKie S, Hallak JE, Williams SR, Dursun SM. Glutamate and the neural basis of the subjective effects of ketamine: a pharmaco-magnetic resonance imaging study. Arch Gen Psychiatry. 2008 Feb;65(2):154-64. doi: 10.1001/archgenpsychiatry.2007.37.

    PMID: 18250253BACKGROUND

  • Fava M. Diagnosis and definition of treatment-resistant depression. Biol Psychiatry. 2003 Apr 15;53(8):649-59. doi: 10.1016/s0006-3223(03)00231-2.

    PMID: 12706951BACKGROUND

  • Lepine JP, Briley M. The increasing burden of depression. Neuropsychiatr Dis Treat. 2011;7(Suppl 1):3-7. doi: 10.2147/NDT.S19617. Epub 2011 May 31.

    PMID: 21750622BACKGROUND

  • Maeng S, Zarate CA Jr, Du J, Schloesser RJ, McCammon J, Chen G, Manji HK. Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biol Psychiatry. 2008 Feb 15;63(4):349-52. doi: 10.1016/j.biopsych.2007.05.028. Epub 2007 Jul 23.

    PMID: 17643398BACKGROUND

  • Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, Schwalb JM, Kennedy SH. Deep brain stimulation for treatment-resistant depression. Neuron. 2005 Mar 3;45(5):651-60. doi: 10.1016/j.neuron.2005.02.014.

    PMID: 15748841BACKGROUND

  • U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Mental Health. (2019). Major Depression. Retrieved from https://www.nimh.nih.gov/health/statistics/major-depression.shtml

    BACKGROUND

  • U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Mental Health. (2018). Depression. Retrieved from https://www.nimh.nih.gov/health/topics/depression/index.shtml

    BACKGROUND

MeSH Terms

Conditions

DepressionDepressive Disorder, Treatment-Resistant

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Behavioral SymptomsBehaviorDepressive DisorderMood DisordersMental Disorders

Intervention Hierarchy (Ancestors)

CyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic Chemicals

Study Officials

  • Sheldon Jordan, MD

    The Neurological Associates of West Los Angeles

    PRINCIPAL INVESTIGATOR

  • Taylor Kuhn, PhD

    The Neurological Associates of West Los Angeles

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: The purpose of this study is to investigate the neuroanatomical effects of ketamine treatment on patients with treatment-resistant depression. We will compare the neuroimaging of patients several days before and after injection in order to assess the more durable changes induced by ketamine. We will analyze changes in perfusion, neurovascular coupling, and functional connectivity that are correlated with psychiatric measures.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 16, 2019

First Posted

December 20, 2019

Study Start

May 2, 2020

Primary Completion

May 28, 2020

Study Completion

May 28, 2020

Last Updated

June 1, 2020

Record last verified: 2020-05

Data Sharing

IPD Sharing
Will not share

Data from this study will not be made publicly available due to ethical and privacy concerns. Anonymized data will be available upon reasonable request from any qualified investigator.

Locations

US(1)