Clinical Trial: Treatment Resistant Depression (Pilot)

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Safe Ketamine-Based Therapy for Treatment Resistant Depression

Brief Summary:

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 be 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).

A subset of 20 patients with TRD will receive a 100-hour (+/- 4-hours)ketamine infusion with head MRIs pre (2) and post (1) infusion. Little research has been done on the mechanism of ketamine's putative antidepressant action. There is now a consensus that, in early stages of the novel treatment development for depressi

Detailed Summary:

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. An additional subset of 20 non-randomized patients, separate from the original randomized clinical trial (RTC), will receive an MRI pre and post ketamine infusion.

1. a. Controlled 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. 100-hour(+/-)IV placebo (saline) infusion
3. a. Controlled 100-hour IV ketamine infusion b. clonidine safener PO prior to infusion c. MRI pre and post ketamine infusion

In both conditions and the neuroimaging subset, 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.

Sponsor: Washington University School of Medicine

Current Primary Outcome: Reduction in (1) Clinical Global Interview (CGI) scores and (2) Montgomery-Asberg Depression Rating Scale (MADRS) scores [ Time Frame: approximately 5 years ]

Original Primary Outcome: reduction in HRSD (depression rating) scores by >50% [ Time Frame: approximately 5 years ]

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Washington University School of Medicine

Dates:
Date Received: August 2, 2010
Date Started: April 2012
Date Completion: June 2016
Last Updated: November 17, 2015
Last Verified: November 2015