Treatment Resistant Depression (Pilot)

September 11, 2023 updated by: Washington University School of Medicine

A Safe Ketamine-Based Therapy for Treatment Resistant Depression

Treatment resistant depression (TRD) is a major public health problem. Current therapeutic options for this patient population remain limited. With all available treatments, only a sub-set of those patients who achieve an antidepressant response are likely to achieve treatment-induced remission. The need for antidepressant medication that can provide both rapid and long lasting relief of TRD symptoms is widely recognized. There is new evidence that drugs that block NMDA glutamate receptors (NMDA antagonists) are promising candidates for meeting this need. Existing studies in TRD have used only a low-dose, brief infusion of ketamine that would not be expected to re-sensitize the NMDA receptor; in agreement with this theory, these prior studies have found only temporary improvements of depression. Our key hypothesis is that a higher-dose, longer-term ketamine infusion, such as that used in chronic pain studies, would provide a more robust and lasting improvement from depression.

Accordingly, we will test whether a 100-hour ketamine infusion would be more effective than the standard 40-minute ketamine infusion currently used in other TRD studies. We will randomize subjects to one of 2 arms: (1) 100-hour (+/- 4 hours) ketamine infusion plus clonidine for the entire infusion (2) 40-minute ketamine infusion (plus clonidine) following a 100+/- hour saline infusion. All subjects will receive clonidine, an alpha-2 agonist, to minimize side effects of ketamine (namely, brief/mild psychotic and cognitive symptoms).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This experiment is a pilot study involving up to 20 healthy males or females between the ages of 18-65 to test whether a 100-hour ketamine infusion plus clonidine would be more effective, with longer lasting results, then the standard 40-minute ketamine infusion (plus clonidine). Each of the 2 arms, will be evaluated using a between subject, double-blind, randomized design.

  1. a. Controlled up to 100-hour IV ketamine infusion b. clonidine safener PO prior to infusion
  2. a. Controlled 40-minute IV ketamine infusion b. clonidine safener PO prior to infusion c. up to 100-hour(+/-)IV placebo (saline) infusion
  3. a. Controlled up to 100-hour IV ketamine infusion b. clonidine safener PO prior to infusion
  4. a.Controlled up to 100-hour IV ketamine infusion b. clonidine safener PO prior to infusion

In both conditions, participants will be admitted to the Washington University School of Medicine Clinical Research Unit at Barnes-Jewish Hospital for approximately 108-hours (Monday morning-Friday evening). Pulse, blood pressure, pulse-oximetry, and an electrocardiogram strip will be routinely monitored. Serial labs and clinical/safety ratings will be done pre-, during, and post-infusion, with the last assessments being used to assure that subjects have returned to their "baseline" prior to discharge from the research unit. Participants will continue to see their primary psychiatrist throughout the study.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion criteria:

  1. males and females aged 18-65 years;
  2. Diagnostic and Statistical Manual (DSM) IV diagnosis of Major Depressive Disorder, recurrent, severe;
  3. depression must be considered treatment refractory as defined by Montgomery Asberg Depression Rating Scale (MADRS) score of 22 or above which is consistent with other studies;
  4. on a stable dose of permitted antidepressant medication or no medication pre-infusion;
  5. not currently psychotic and no history of psychosis within the previous 12 months; psychosis reported in the distant past may not be exclusionary if brief, per PI's judgment;
  6. no history of significant clinical or intolerable side effects or complications from clonidine;
  7. if a female of child-bearing potential: not pregnant or breast feeding and agrees to use birth control during the time of pre-dosing and infusions; and
  8. able to give informed consent.

Exclusion Criteria:

  1. confirmed bipolar disorder, schizophrenia, or schizoaffective disorder;
  2. current or recent substance abuse/dependence (or any lifetime recreational ketamine or PCP use);
  3. any severe Axis II personality disorder or schizophrenia spectrum disorder that, in the PI's judgment, could confound diagnosis or adherence to treatment;
  4. the presence of any abnormal laboratory findings or serious medical disorder or condition that may, in the judgment of the PI, confound the assessment of relevant biologic measures or diagnoses including: clinically significant organ system dysfunction; significant and uncontrolled endocrine disease, including diabetes mellitus; hypothyroidism; cardiovascular disease; coagulopathy; significant anemia; significant acute infection; glaucoma; dehydration; epilepsy; any diagnosed cardiac condition causing documented hemodynamic compromise or dysfunction of the SA or AV node; any diagnosed respiratory condition causing documented or clinically recognized hypoxia (e.g., chronic obstructive or restrictive pulmonary disease); after evaluation, anyone determined to have a potentially compromised airway that could be difficult to intubate; fever; BMI less than 14.5; or any medical condition known to interfere with cognitive performance; medication-related exclusions include memantine, or any medication that could be considered contraindicated ketamine;
  5. current treatment with any medication contraindicated with ketamine or clonidine;
  6. lifetime illegal use of PCP or ketamine; no clinical use of ketamine for past 3 months
  7. meets DSM-IV criteria for Mental Retardation;
  8. currently hospitalized;
  9. acutely suicidal or homicidal (i.e., in imminent danger with plan, urges and intent to harm oneself or others) including any prior serious attempts (e.g., those requiring hospitalization) at the PI's discretion;
  10. is pregnant or breast-feeding; unwilling to use birth control if female of child bearing potential
  11. unable to provide informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ketamine 100-hour infusion
100-hour infusion of ketamine plus a safener (clonidine)
Drug: Clonidine
Participants will receive an approximately 5-day pretreatment of clonidine (max. dose 1mg/day divided doses) prior to and throughout the ketamine infusion.
Other Names:
  • Catapares
Drug: Ketamine
Controlled IV ketamine infusion (0.00225mg/kg-min. [18% (0.0125 mg/kg-min.).
Other Names:
  • Ketalar
  • Ketalin
  • Ketalor
Active Comparator: ketamine 40-minute infusion
40-minute ketamine infusion following a 100-hours +/- placebo (saline) infusion. Participants will also receive a safener (clonidine)
Drug: Clonidine
Participants will receive an approximately 5-day pretreatment of clonidine (max. dose 1mg/day divided doses) prior to and throughout the ketamine infusion.
Other Names:
  • Catapares
Drug: placebo
IV saline (i.e. placebo ketamine)
Other Names:
  • saline
Drug: Ketamine
Controlled IV ketamine infusion (0.00225mg/kg-min. [18% (0.0125 mg/kg-min.).
Other Names:
  • Ketalar
  • Ketalin
  • Ketalor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Time Frame: 8 weeks
The Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item scale that measures the severity of depression, with a higher score indicating a higher level of depression. The range of scores is 0 to 60.
8 weeks
Clinical Global Impression (CGI) Global Improvement Score.
Time Frame: 8 weeks
The Clinical Global Improvement is a 7-point scale where the anchors range from 1 (very much improved) to 7 (very much worse).
8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Collaborators

Florida Atlantic University

Investigators

  • Principal Investigator: John W Newcomer, MD, Washington University School of Medicine
  • Principal Investigator: Nuri B Farber, MD, Washington University School of Medicine
  • Principal Investigator: Eric Lenze, MD, Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2012

Primary Completion (Actual)

June 6, 2014

Study Completion (Actual)

June 5, 2015

Study Registration Dates

First Submitted

August 2, 2010

First Submitted That Met QC Criteria

August 9, 2010

First Posted (Estimated)

August 10, 2010

Study Record Updates

Last Update Posted (Actual)

September 15, 2023

Last Update Submitted That Met QC Criteria

September 11, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 201202157

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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