A Study of Ketamine as an Antidepressant

• ClinicalTrials.gov Identifier: NCT01441505
• Recruitment Status: Unknown
• First Posted: September 27, 2011
• Last Update Posted: February 22, 2013
• Sponsor: The University of New South Wales
• Collaborator: Wesley Mission
• Information provided by (Responsible Party): Colleen Loo, The University of New South Wales

Tracking Information

• First Submitted Date: September 16, 2011
• First Posted Date: September 27, 2011
• Last Update Posted Date: February 22, 2013
• Study Start Date: September 2011
• Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 25, 2011): Change from baseline on depression rating scales [ Time Frame: Before, 4 hours after, and 24 hours after ketamine session ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: September 25, 2011): Psychiatric side effects (BPRS, CADSS) and memory tests [ Time Frame: Cognitive battery done before and after 3 weeks; side effects measured immediately before and 4 hours after each ketamine session in both phases. ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Ketamine as an Antidepressant
• Official Title: A Study of Ketamine as an Antidepressant

Brief Summary

Recently, interest has emerged in the use of ketamine as an antidepressant. Recent placebo-controlled clinical trials administering a single dose and an open label trial giving repeated doses shown that ketamine is markedly superior to placebo at reducing depression, including in treatment-resistant patients, and that its antidepressant effects have a very rapid onset.

This clinical study consists of two phases. In Phase I, participants who satisfy inclusion criteria will receive ketamine at variable doses (0.1mg/kg-0.5mg/kg) or a placebo (saline, or 0.01mg/kg midazolam) once a week over up to 6 weeks. If participants qualify for Phase II, they will receive repeated sessions of ketamine at variable doses over three weeks. During both phases, mood, psychiatric, and neuropsychological outcomes will be measured.

Detailed Description

This clinical study consists of two phases. In Phase I, participants will receive variable doses of intravenous, intramuscular, or subcutaneous ketamine (0.1-0.5mg/kg) or placebo (saline, or 0.01mg/kg midazolam) weekly for up to 6 consecutive weeks. Prior to receiving ketamine/placebo, participants' mood and psychiatric symptoms will be assessed. Once they have received their treatment, mood, psychiatric side effects, ketamine blood levels, heart rate, blood pressure and biomarkers will be assessed. Mood and cognitive performance be assessed again after 4 hours. Finally, mood will also be assessed the next day.

Some participants may be eligible to continue to Phase II. In this phase, participants will receive doses of ketamine approximately weekly for up to 6 months. During this phase, participants' mood, psychiatric, biomarkers and cognitive outcomes will be assessed.

The purpose of the trial is to investigate the antidepressant and safety effects of using ketamine as a treatment in depression.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Major Depressive Episode

Intervention

• Drug: Ketamine
  Ketamine IV, IM, or SC will be administered in Phase I and II
• Drug: Saline or Midazolam (active placebo)
  Saline, or midazolam 0.01mg/kg will be administered in Phase I

• Study Arms: Not Provided

Publications *

• aan het Rot M, Collins KA, Murrough JW, Perez AM, Reich DL, Charney DS, Mathew SJ. Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression. Biol Psychiatry. 2010 Jan 15;67(2):139-45. doi: 10.1016/j.biopsych.2009.08.038.
• 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.
• Diazgranados N, Ibrahim L, Brutsche NE, Newberg A, Kronstein P, Khalife S, Kammerer WA, Quezado Z, Luckenbaugh DA, Salvadore G, Machado-Vieira R, Manji HK, Zarate CA Jr. A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression. Arch Gen Psychiatry. 2010 Aug;67(8):793-802. doi: 10.1001/archgenpsychiatry.2010.90.
• Larkin GL, Beautrais AL. A preliminary naturalistic study of low-dose ketamine for depression and suicide ideation in the emergency department. Int J Neuropsychopharmacol. 2011 Sep;14(8):1127-31. doi: 10.1017/S1461145711000629. Epub 2011 May 5. Retraction in: Int J Neuropsychopharmacol. 2017 Jul 1;20(7):611.
  Retraction in:Int J Neuropsychopharmacol. 2017 Jul 1;20(7):611
• 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.
• George D, Gálvez V, Martin D, Kumar D, Leyden J, Hadzi-Pavlovic D, Harper S, Brodaty H, Glue P, Taylor R, Mitchell PB, Loo CK. Pilot Randomized Controlled Trial of Titrated Subcutaneous Ketamine in Older Patients with Treatment-Resistant Depression. Am J Geriatr Psychiatry. 2017 Nov;25(11):1199-1209. doi: 10.1016/j.jagp.2017.06.007. Epub 2017 Jun 13.
• Loo CK, Gálvez V, O'Keefe E, Mitchell PB, Hadzi-Pavlovic D, Leyden J, Harper S, Somogyi AA, Lai R, Weickert CS, Glue P. Placebo-controlled pilot trial testing dose titration and intravenous, intramuscular and subcutaneous routes for ketamine in depression. Acta Psychiatr Scand. 2016 Jul;134(1):48-56. doi: 10.1111/acps.12572. Epub 2016 Mar 30.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: October 3, 2011): 42
• Original Estimated Enrollment (submitted: September 25, 2011): 28
• Estimated Study Completion Date: December 2014
• Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Satisfy DSM-IV-TR criteria for Major Depressive Episode
• 18 years or over
• Able to give informed consent

Exclusion Criteria:

• Diagnosis of schizophrenia, schizoaffective disorder, rapid cycling bipolar disorder, or current psychotic symptoms
• Known sensitivity or contraindication to ketamine
• Recent drug abuse
• Pregnant

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia

Administrative Information

• NCT Number: NCT01441505
• Other Study ID Numbers: HREC 10409
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Colleen Loo, The University of New South Wales
• Study Sponsor: The University of New South Wales
• Collaborators: Wesley Mission

Investigators

• Principal Investigator: Colleen K Loo, MB BS FRANZCP MD; University of New South Wales

• PRS Account: The University of New South Wales
• Verification Date: February 2013