Clinical trial NCT04205890: Intravenous Ketamine Effects on Functional Neuroanatomy
Official title: Intravenous Ketamine Effects on Functional Neuroanatomy
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Depression
Keywords: intravenous ketamine
treatment-resistant depression
Lead sponsor: Neurological Associates of West Los Angeles
Sponsor class: OTHER
First posted: 2019-12-20
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Detailed description: 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. Patients will be examined by the principle investigator. All patients must be diagnosed with persistent treatment-resistant depression and prescribed ketamine. Patients will be accepted regardless of if the depression coincided with anxiety and/or pain. Patient status will be assessed using the Beck Depression Inventory, Beck Anxiety Inventory, and Brief Pain Inventory. Patients must have a Beck Depression Inventory score of 10 or above. These scores will be used as baseline data. Patients will be offered the option of participating in the study and provided informed consent for neuroimaging before and after the ketamine treatment.

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; dosages varies between 75mg - 1000mg depending on every individual's unique treatment plan. The same scans will be taken two days after treatment.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: fMRI T1 baseline
timeFrame: Images to be acquired 7 days prior to Ketamine intervention
measure: fMRI T1 post-intervention comparison
timeFrame: Images to be acquired at 2 days post-treatment
measure: Arterial Spin Labeling (fMRI) baseline
timeFrame: Images to be acquired 7 days prior to Ketamine intervention
measure: Arterial Spin Labeling (fMRI) post-intervention comparison
timeFrame: Images to be acquired at 2 days post-treatment
measure: fMRI Resting Bold baseline
timeFrame: Images to be acquired 7 days prior to Ketamine intervention
measure: fMRI Resting Bold post-intervention comparison
timeFrame: Images to be acquired at 2 days post-treatment
Secondary outcomes:
measure: Beck Depression Inventory
timeFrame: 7 days prior to treatment
measure: Beck Depression Inventory
timeFrame: Day of treatment
measure: Beck Depression Inventory
timeFrame: 2 days after treatment
measure: Beck Anxiety Inventory
timeFrame: 7 days prior to treatment
measure: Beck Anxiety Inventory
timeFrame: Day of treatment
measure: Beck Anxiety Inventory
timeFrame: 2 days after treatment
measure: Brief Pain Inventory
timeFrame: 7 days prior to treatment
measure: Brief Pain Inventory
timeFrame: Day of Treatment
measure: Brief Pain Inventory
timeFrame: 2 days post-treatment
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Neurological Associates of West Los Angeles
state: California
Study officials:
affiliation: The Neurological Associates of West Los Angeles
name: Sheldon Jordan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Neurological Associates of West Los Angeles
name: Taylor Kuhn, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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
citation: 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