Clinical trial NCT01179009
Conditions: Depressive Disorder, Treatment-Resistant
Keywords: depression
Sponsor: Washington University School of Medicine
Start date: 2012-04-01; Completion date: 2015-06-05
Enrollment: 20 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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 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).

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.

Arms: arm 1: 100-hour infusion of ketamine plus a safener (clonidine) arm 2: 40-minute ketamine infusion following a 100-hours +/- placebo (saline) infusion. Participants will also receive a safener (clonidine)
Interventions: intervention 1: Ketamine intervention 2: Clonidine intervention 3: placebo
Intervention descriptions: intervention 1: Controlled IV ketamine infusion (0.00225mg/kg-min. \[18% (0.0125 mg/kg-min.). intervention 2: Participants will receive an approximately 5-day pretreatment of clonidine (max. dose 1mg/day divided doses) prior to and throughout the ketamine infusion. intervention 3: IV saline (i.e. placebo ketamine)

Protocol documents: