Optimization of IV Ketamine for Treatment Resistant Depression

NCT00768430 | Completed Phase 2 Results DMC

• 1 other identifier: GCO 07-0114
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 2

Brief Summary

Existing treatments for major depressive disorder (MDD) generally take weeks to months to exert their maximal benefit. There is an urgent need to develop rapid-acting treatments for MDD. Ketamine, a high-affinity N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, has been used as a standard intravenous (IV) anesthetic agent for many years in both pediatric and adult patients. Beyond its well-established role in anesthesia and pain management, there is emerging evidence that ketamine may have rapid antidepressant properties for patients with severe mood disorders. In this study we are investigating whether ketamine can have an antidepressant effect compared to midazolam. Midazolam has similar anesthetic effects compared to ketamine but has not been shown to be an antidepressant, and is therefore acting as an active control in this study. The study period can last up to 8 weeks, depending on your response to the study medication. There are two required overnight stays in our Research Commons as part of this study.

Conditions

Major Depressive Disorder (MDD); Treatment Resistant Depression (TRD)

Outcome Measures

Primary Outcomes (1)

• MADRS

  Montgomery-Asberg Depression Rating Scale, each of the ten items can be scored from 0 (absence of symptoms to 6 most severe) and has a total score range of 0-60. A lower score on a MADRS indicates a less severe depression.

  24 hours post-infusion

Study Arms (2)

1

EXPERIMENTAL

Ketamine

Drug: Ketamine

2

ACTIVE COMPARATOR

Midazolam

Drug: Midazolam

Interventions

Ketamine DRUG

Single dose .5 mg/kg IV (in the vein) infused over 40 minutes

Also known as: Racemic ketamine hydrochloride

1

Midazolam DRUG

single dose 0.045 mg/kg IV infused over 40 minutes

2

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients, 21-80 years of age;
• Female individuals who are not of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year) or using a medically accepted reliable means of contraception. Women using oral contraceptive medication for birth control must also be using a barrier contraceptive. Women of childbearing potential must also have a negative serum beta-human growth hormone at screening and at pre-infusion;
• Participants must fulfill DSM-IV criteria for Major Depression without psychotic features, based on clinical assessment by a study psychiatrist and confirmed by a structured diagnostic interview, the Structured Clinical Interview for DSM-IV TR Axis I Disorders, Patient Edition (SCID-P);
• Participants must have a history of at least one previous episode of depression prior to the current episode (recurrent MDD) or have chronic MDD (of at least two years' duration);
• Participants have not responded to three or more adequate trials of an antidepressant as determined by Antidepressant Treatment History Form (ATHF) criteria (score \>=3);
• Participant scores on the IDS-C30 must be greater than or equal to 32 at both Screening and within 24 hours prior to Visit 1a (Phase 1);
• Current major depressive episode is of at least 4 weeks duration.
• Each participant must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document;
• Each participant must be able to identify a family member, physician, or friend who will participate in the Treatment Contract.

You may not qualify if:

• Lifetime history of psychotic features, diagnosis of schizophrenia or any other psychotic disorder, or diagnosis of bipolar disorder
• Lifetime histories of autism, mental retardation, pervasive developmental disorders, or Tourette's syndrome;
• Current diagnosis of Obsessive Compulsive Disorder or eating disorder (bulimia nervosa or anorexia nervosa);
• Subjects with DSM-IV drug or alcohol abuse/dependence within the preceding 2 years;
• Patients with schizotypal or antisocial personality disorder, or any clinically significant axis II disorder that would, in the investigator's judgment, preclude safe study participation;
• Patients judged clinically to be at serious and imminent suicidal or homicidal risk;
• Women who are either pregnant or nursing;
• Serious, unstable medical illnesses including hepatic, renal, gastroenterologic (including gastroesophageal reflux disease), respiratory (including obstructive sleep apnea, or history of difficulty with airway management during previous anesthetics), cardiovascular (including ischemic heart disease and uncontrolled hypertension), endocrinologic, neurologic (including history of severe head injury), immunologic, or hematologic disease;
• Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG;
• Patients with one or more seizures without a clear and resolved etiology;
• Patients starting hormonal treatment (e.g., estrogen) in the last 3 months prior to Visit 1a;
• Treatment with an irreversible MAOI or any other FDA approved Anti depressant medication within one week prior to Visit 1a (with the exception of a stable dose of non-benzodiazepines hypnotics i.e. zolpidem, eszopiclone, etc for at least 3 months);
• Treatment with fluoxetine within 4 weeks prior to Visit 1a;
• Evidence-based individual psychotherapy (e.g. CBT or IPT) and other non-pharmacological antidepressant treatments (e.g. light therapy) will not be permitted during the acute study period (7 day);
• Previous recreational use of PCP or Ketamine.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Icahn School of Medicine at Mount Sinai: collaborator

Study Sites (2)

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Michael E. Dabakey VA Medical Center & Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Related Publications (4)

• Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006 Aug;63(8):856-64. doi: 10.1001/archpsyc.63.8.856.

  PMID: 16894061 BACKGROUND

• Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000 Feb 15;47(4):351-4. doi: 10.1016/s0006-3223(99)00230-9.

  PMID: 10686270 BACKGROUND

• Wan LB, Levitch CF, Perez AM, Brallier JW, Iosifescu DV, Chang LC, Foulkes A, Mathew SJ, Charney DS, Murrough JW. Ketamine safety and tolerability in clinical trials for treatment-resistant depression. J Clin Psychiatry. 2015 Mar;76(3):247-52. doi: 10.4088/JCP.13m08852.

  PMID: 25271445 DERIVED

• Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Green CE, Perez AM, Iqbal S, Pillemer S, Foulkes A, Shah A, Charney DS, Mathew SJ. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry. 2013 Oct;170(10):1134-42. doi: 10.1176/appi.ajp.2013.13030392.

  PMID: 23982301 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant

Interventions

Ketamine; Midazolam

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Limitations of our trial include stringent enrollment criteria due to concerns about ketamine's psychoactive effects and abuse liability. A proportion of screened patients (17.2%) refused or were unable to tolerate psychotropic washout.

Results Point of Contact

• Title: Dr. Sanjay Mathew
• Organization: Baylor College of Medicine

sjmathew@bcm.edu

7137911414

Study Officials

• Sanjay J. Mathew, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

• Dan V Iosifescu, MD,M.Sc.

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: October 7, 2008
• First Posted: October 8, 2008
• Study Start: November 1, 2008
• Primary Completion: September 1, 2012
• Study Completion: November 1, 2012
• Last Updated: January 31, 2014
• Results First Posted: January 31, 2014

Record last verified: 2013-12

Locations

US (2)