Biomarkers of Fast Acting Therapies in Major Depression

NCT02165449 | Completed Phase 1 DMC

• 3 other identifiers: HS001796K24MH102743U01MH110008
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The drug Ketamine, available in medical practice since the late 1960s, is currently used for inducing general anesthesia or sedation during medical procedures. When given slowly as an injection into a vein, ketamine is shown to produce a very rapid effect on depression and to improve depressive symptoms within hours to days. By studying patients who receive a ketamine IV infusion, as an add-on treatment for depression, investigators may start to understand how changes in the brain or in gene function relate to getting better over a very short period of time. In this study, the investigators will enroll 60 patients currently ill with major depression selected to receive IV ketamine therapy under medical supervision. To study neurobiological changes relating to symptom improvement, the investigators will use advanced brain scans to measure brain structure, chemistry and function. Blood samples will measure changes in gene regulation and immune system response. Although some people have a rapid antidepressant response to ketamine, others do not respond. Also, antidepressant effects after ketamine usually wear off within days to weeks. We will determine if up to four doses of ketamine delivered two to three times a week may prolong antidepressant response to ketamine therapy. To determine the durability of ketamine treatment for depression, patients will be monitored by phone and via electronic devices twice a week for up to five weeks and will return for a final assessment when their symptoms return. For this trial, brain and blood sample measurements will occur before and after a patient receives their first ketamine infusion. Patients who do not remit after an initial dose of ketamine, will receive up to three additional ketamine treatments. Mood will be measured 24-hours after each subsequent ketamine infusion and brain and blood measurements be repeated at the time of remission or after the fourth ketamine infusion if remission does not occur. Patients will return for a final brain scan and blood sample when their depressive symptoms return or at five weeks if they continue remission. Investigators will able to see how changes brain measurements, gene regulation and immune response relate to improvements and relapse of depressive symptoms with ketamine IV therapy. The ketamine infusion sessions will occur at a special research unit (CTRC) at UCLA.

Conditions

Major Depressive Disorder

Keywords

ketamine; major depression; imaging; gene expression

Outcome Measures

Primary Outcomes (2)

• Change in the Hamilton Depression Rating Scale measured between baseline and 24 hrs following the first ketamine infusion treatment, and 24 hrs following up to three additional ketamine infusions

  Change in mood ratings from the Hamilton Depression Rating Scale

  up to 2 weeks

• Change in the Hamilton Depression Rating Scale measured between the last ketamine infusion treatment and 5 week follow-up

  Change in mood ratings from the Hamilton Depression Rating Scale

  5 weeks

Secondary Outcomes (8)

• Change in gene expression measured between baseline and 24 hrs following the first ketamine infusion treatment, and 24 hrs following up to three additional ketamine infusions

  up to 2 weeks

• Change in gene expression measured between the last ketamine infusion treatment and 5 week follow-up

  5 weeks

• Change in non-invasive Magnetic Resonance Imaging measures of structural connectivity measured between baseline and 24 hrs following the first ketamine infusion treatment, and 24 hrs following up to three additional ketamine infusions

  up to 2 weeks

• Change in non-invasive Magnetic Resonance Imaging measures of structural connectivity measured between the last ketamine infusion treatment and at 5 weeks

  5 weeks

• Change in non-invasive Magnetic Resonance Imaging measures of functional connectivity measured between baseline and 24 hrs following the first ketamine infusion treatment, and 24 hrs following up to three additional ketamine infusions

  up to 2 weeks

Study Arms (1)

Ketamine

EXPERIMENTAL

Drug: Ketamine

Interventions

Ketamine DRUG

Approved FDA indications for ketamine include use as an adjunct in the induction and maintenance of general anesthesia and for procedural sedation. For general anesthesia, ketamine is given at dosages ranging from 1-2mg/kg and given either as bolus injection or run continuously (0.1 to 0.3mg/kg/min) in conjunction with another anesthetic or sedation agent. In this study, ketamine at a subanesthetic dose of 0.5mg/kg will be diluted in 60cc of normal saline and administered via a slow IV infusion over 40 minutes at each treatment session in patients while undergoing hemodynamic monitoring. When used in this manner, ketamine infusion does not induce general anesthesia or states of unconsciousness, and patients remain fully awake, responsive to commands, and do not lose respiratory drive.

Ketamine

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age between 18 to 64 years, inclusive
• Diagnosis: DSM-IV TR criteria for non-psychotic major depression
• Hamilton Depression Rating Scale-17 item ≥ 18 or Montgomery Asberg Depression Scale ≥ 20
• A history of at least one previous major depressive episode prior to the current episode
• Recurrent Depression - in the current episode, have not responded to at least 2 adequate antidepressant trials (using Antidepressant Treatment History Form criteria)
• Have been continuously depressed for between 6-12 months
• Receiving approved monoaminergic antidepressant therapy
• No changes in antidepressant medication(s) in the past one (1) month
• Voluntary patient receiving ketamine
• Capacity to provide informed consent
• Have no contraindications to an adjunctive trial of ketamine infusion
• Be under the current care of a treating Psychiatrist
• If outpatient, a responsible driver available for transportation to and from scanning sessions
• Live locally, within travelling distance to UCLA
• Be available to participate for a 5-week research follow-up

You may not qualify if:

• Younger than 18 or older than 64
• Serious and imminent suicidal or homicidal risk (active suicidal ideations with or without a plan, HAM-D score ≥ 3 on item 3)
• Mental retardation or other developmental disorder
• Diagnosis of dementia of any type
• History of current substance abuse or dependence
• Psychotic reactions to medications, alcohol or illicit substances in the past
• Current or past history of psychosis, schizophrenia, bipolar disorder, delusional disorder or other psychotic disorder
• Treatment with medications with NMDA and NMDAR action
• Contraindication to ketamine
• Depression related to serious medical illness (i.e., mood disorder due to general medical condition)
• History of neurological disorder or other physical disorder (i.e. significant head injury) that could affect brain functioning
• Serious or unstable medical or neurological condition(s) that in the opinion of the treating physician or PI renders ketamine unsafe to administer
• Any condition that would contraindicate scanning (metal implants, claustrophobia or a breathing or movement disorder)
• Pregnancy (as confirmed by positive urine pregnancy test) or planning on becoming pregnant
• Non-English speaking (due to scales administered)

Sponsors & Collaborators

• University of California, Los Angeles: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Geffen School of Medicine, UCLA

Los Angeles, California, 90095, United States

Location

Related Publications (2)

• Vasavada MM, Loureiro J, Kubicki A, Sahib A, Wade B, Hellemann G, Espinoza RT, Congdon E, Narr KL, Leaver AM. Effects of Serial Ketamine Infusions on Corticolimbic Functional Connectivity in Major Depression. Biol Psychiatry Cogn Neurosci Neuroimaging. 2021 Jul;6(7):735-744. doi: 10.1016/j.bpsc.2020.06.015. Epub 2020 Jul 3.

  PMID: 32900657 DERIVED

• Sahib AK, Loureiro JRA, Vasavada MM, Kubicki A, Joshi SH, Wang K, Woods RP, Congdon E, Wang DJJ, Boucher ML, Espinoza R, Narr KL. Single and repeated ketamine treatment induces perfusion changes in sensory and limbic networks in major depressive disorder. Eur Neuropsychopharmacol. 2020 Apr;33:89-100. doi: 10.1016/j.euroneuro.2020.01.017. Epub 2020 Feb 12.

  PMID: 32061453 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Katherine Narr, Ph.D.

  Geffen School of Medicine, University of California, Los Angeles (UCLA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Neurology

Study Record Dates

• First Submitted: June 12, 2014
• First Posted: June 17, 2014
• Study Start: June 1, 2014
• Primary Completion: August 1, 2019
• Study Completion: August 1, 2019
• Last Updated: August 28, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will share

Locations

US (1)