Optimization of IV Ketamine for Treatment Resistant Depression

• ClinicalTrials.gov Identifier: NCT00768430
• Recruitment Status: Completed
• First Posted: October 8, 2008
• Results First Posted: January 31, 2014
• Last Update Posted: January 31, 2014
• Sponsor: Baylor College of Medicine
• Collaborator: Icahn School of Medicine at Mount Sinai
• Information provided by (Responsible Party): Sanjay Johan Mathew, Baylor College of Medicine

Tracking Information

• First Submitted Date: October 7, 2008
• First Posted Date: October 8, 2008
• Results First Submitted Date: September 5, 2013
• Results First Posted Date: January 31, 2014
• Last Update Posted Date: January 31, 2014
• Study Start Date: November 2008
• Actual Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 27, 2013)

MADRS [ Time Frame: 24 hours post-infusion ]

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.

• Original Primary Outcome Measures (submitted: October 7, 2008): MADRS [ Time Frame: 40 minutes, 120 minutes, 24 hours, 7 days ]
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Optimization of IV Ketamine for Treatment Resistant Depression
• Official Title: Optimization of Intravenous Ketamine for Treatment-Resistant Depression: A Randomized, Placebo-Controlled, Triple-masked, Clinical Trial

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

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

Intervention

• Drug: Ketamine
  Single dose .5 mg/kg IV (in the vein) infused over 40 minutes
  Other Name: Racemic ketamine hydrochloride
• Drug: Midazolam
  single dose 0.045 mg/kg IV infused over 40 minutes

Study Arms

• Experimental: 1
  Ketamine
  Intervention: Drug: Ketamine
• Active Comparator: 2
  Midazolam
  Intervention: Drug: Midazolam

Publications *

• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 8, 2013): 73
• Original Estimated Enrollment (submitted: October 7, 2008): 64
• Actual Study Completion Date: November 2012
• Actual Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Male or female patients, 21-80 years of age;
2. 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;
3. 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);
4. 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);
5. Participants have not responded to three or more adequate trials of an antidepressant as determined by Antidepressant Treatment History Form (ATHF) criteria (score >=3);
6. 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);
7. Current major depressive episode is of at least 4 weeks duration.
8. 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;
9. Each participant must be able to identify a family member, physician, or friend who will participate in the Treatment Contract.

Exclusion Criteria:

1. Lifetime history of psychotic features, diagnosis of schizophrenia or any other psychotic disorder, or diagnosis of bipolar disorder
2. Lifetime histories of autism, mental retardation, pervasive developmental disorders, or Tourette's syndrome;
3. Current diagnosis of Obsessive Compulsive Disorder or eating disorder (bulimia nervosa or anorexia nervosa);
4. Subjects with DSM-IV drug or alcohol abuse/dependence within the preceding 2 years;
5. 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;
6. Patients judged clinically to be at serious and imminent suicidal or homicidal risk;
7. Women who are either pregnant or nursing;
8. 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;
9. Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG;
10. Patients with one or more seizures without a clear and resolved etiology;
11. Patients starting hormonal treatment (e.g., estrogen) in the last 3 months prior to Visit 1a;
12. 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);
13. Treatment with fluoxetine within 4 weeks prior to Visit 1a;
14. 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);
15. Previous recreational use of PCP or Ketamine.
16. Past intolerance or hypersensitivity to midazolam
17. Hypertension (systolic BP >160 mm Hg or diastolic BP >90 mm Hg) not controlled by diuretic or beta-blocker therapy alone or in combination.
18. Evidence of age-related cognitive decline or mild dementia suggested by a score of < 27 on the Mini-Mental State Examination (MMSE) at Screening

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00768430
• Other Study ID Numbers: GCO 07-0114
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Sanjay Johan Mathew, Baylor College of Medicine
• Original Responsible Party: Sanjay Mathew, MD, Mount Sinai School of Medicine
• Current Study Sponsor: Baylor College of Medicine
• Original Study Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: Icahn School of Medicine at Mount Sinai

Investigators

• Principal Investigator: Sanjay J. Mathew, MD; Baylor College of Medicine
• Principal Investigator: Dan V Iosifescu, MD,M.Sc.; Icahn School of Medicine at Mount Sinai

• PRS Account: Baylor College of Medicine
• Verification Date: December 2013