Treatment Resistant Depression (Pilot)

NCT01179009 | Completed Results DMC

• 1 other identifier: 201202157
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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).

Conditions

Depressive Disorder, Treatment-Resistant

Keywords

depression

Outcome Measures

Primary Outcomes (2)

• Montgomery-Asberg Depression Rating Scale (MADRS) Total Score

  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.

  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

Study Arms (2)

ketamine 100-hour infusion

EXPERIMENTAL

100-hour infusion of ketamine plus a safener (clonidine)

Drug: Ketamine; Drug: Clonidine

ketamine 40-minute infusion

ACTIVE COMPARATOR

40-minute ketamine infusion following a 100-hours +/- placebo (saline) infusion. Participants will also receive a safener (clonidine)

Drug: Ketamine; Drug: Clonidine; Drug: placebo

Interventions

Ketamine DRUG

Controlled IV ketamine infusion (0.00225mg/kg-min. \[18% (0.0125 mg/kg-min.).

Also known as: Ketalar, Ketalin, Ketalor

ketamine 100-hour infusion; ketamine 40-minute infusion

Clonidine DRUG

Participants will receive an approximately 5-day pretreatment of clonidine (max. dose 1mg/day divided doses) prior to and throughout the ketamine infusion.

Also known as: Catapares

ketamine 100-hour infusion; ketamine 40-minute infusion

placebo DRUG

IV saline (i.e. placebo ketamine)

Also known as: saline

ketamine 40-minute infusion

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• males and females aged 18-65 years;
• Diagnostic and Statistical Manual (DSM) IV diagnosis of Major Depressive Disorder, recurrent, severe;
• 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;
• on a stable dose of permitted antidepressant medication or no medication pre-infusion;
• no history of significant clinical or intolerable side effects or complications from clonidine;
• 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
• able to give informed consent.

You may not qualify if:

• confirmed bipolar disorder, schizophrenia, or schizoaffective disorder;
• current or recent substance abuse/dependence (or any lifetime recreational ketamine or PCP use);
• any severe Axis II personality disorder or schizophrenia spectrum disorder that, in the PI's judgment, could confound diagnosis or adherence to treatment;
• current treatment with any medication contraindicated with ketamine or clonidine;
• lifetime illegal use of PCP or ketamine; no clinical use of ketamine for past 3 months
• meets DSM-IV criteria for Mental Retardation;
• currently hospitalized;
• 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;
• is pregnant or breast-feeding; unwilling to use birth control if female of child bearing potential
• unable to provide informed consent.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Florida Atlantic University: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

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MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depression

Interventions

Ketamine; Clonidine; Sodium Chloride

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazolines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

A pilot and feasibility study with limited statistical power due to a small sample size. Another limitation was the lack of a scale specifically measuring dissociative symptoms. In addition, the allowance of co-occurring antidepressant use could result in increased heterogeneity of responses unrelated to the study medication. Finally, the sample was ethnically homogeneous.

Results Point of Contact

• Title: Michael Yingling
• Organization: Washington University

yinglinm@wustl.edu

5735791412

Study Officials

• Eric Lenze, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

• John W Newcomer, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

• Nuri B Farber, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2010
• First Posted: August 10, 2010
• Study Start: April 1, 2012
• Primary Completion: June 6, 2014
• Study Completion: June 5, 2015
• Last Updated: September 15, 2023
• Results First Posted: September 15, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)