A Study of Ketamine as an Antidepressant

Tracking Information
First Submitted Date ICMJE	September 16, 2011
First Posted Date ICMJE	September 27, 2011
Last Update Posted Date	February 22, 2013
Study Start Date ICMJE	September 2011
Estimated Primary Completion Date	December 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (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 ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01441505 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (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 ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	A Study of Ketamine as an Antidepressant
Official Title ICMJE	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 ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Major Depressive Episode
Intervention ICMJE	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.; 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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Unknown status
Estimated Enrollment ICMJE; (submitted: October 3, 2011)	42
Original Estimated Enrollment ICMJE; (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 ICMJE	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, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Australia
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01441505
Other Study ID Numbers ICMJE	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 ICMJE	The University of New South Wales
Collaborators ICMJE	Wesley Hospital, Kogarah
Investigators ICMJE	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
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP