Clinical Trial of the Use of Ketamine in Treatment Resistant Depression

NCT02610712 | Unknown Phase 4

• 1 other identifier: 63/13
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the efficacy of the use of intravenous low-dose ketamine in the treatment of treatment-resistant depression (TRD), as well as the changes in Glutamate neurotransmission and inflammatory serum markers.

Conditions

Depressive Disorder, Treatment-Resistant

Keywords

ketamine; treatment-resistant; depression; spectroscopy; neuroinflammation

Outcome Measures

Primary Outcomes (1)

• Hamilton Depression Rating Scale (HDRS) Score

  Change from baseline HDRS Score at 24 hours

Secondary Outcomes (2)

• Glutamate concentrations in the pregenual cingulate cortex (pgACC)

  Change from baseline Glutamate concentrations in the pgACC at 24 hours

• Interleukin-1 (IL-1) and Tumoral Necrosis Factor-alpha (TNF-alpha) serum concentrations

  Change from baseline IL-1 and TNF-alpha serum concentrations from baseline at 24 hours

Study Arms (1)

TRD patients

EXPERIMENTAL

Treatment-Resistant (TRD) patients to receive intravenous ketamine at 0.5 mg/kg dose.

Drug: Ketamine

Interventions

Ketamine DRUG

TRD patients

Eligibility Criteria

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

You may qualify if:

• Treatment-Resistant Depression (Failure to respond to two or more trials of antidepressant monotherapy or failure to respond to four or more trials of different antidepressant therapies)
• Acceptance of participation via the informed consent

You may not qualify if:

• Psychiatric comorbidity (except anxiety related disorders)
• Substance abuse or dependence in the previous 3 months
• Evidence of structural abnormalities in brain imaging
• Pregnancy
• Previous hypersensitivity to ketamine
• Heart failure or insufficiency
• Familial or personal history of psychosis
• Glaucoma
• Major neurological disease
• Uncontrolled systemic arterial hypertension
• MRI contraindications
• Non-acceptance of participation via informed consent

Sponsors & Collaborators

• National Institute of Neurology and Neurosurgery, Mexico: lead

Study Sites (1)

National Institute of Neurology and Neurosurgery

Mexico City, Mexico City, 14269, Mexico

RECRUITING

Related Publications (13)

• 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

• DiazGranados N, Ibrahim LA, Brutsche NE, Ameli R, Henter ID, Luckenbaugh DA, Machado-Vieira R, Zarate CA Jr. Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatment-resistant major depressive disorder. J Clin Psychiatry. 2010 Dec;71(12):1605-11. doi: 10.4088/JCP.09m05327blu. Epub 2010 Jul 13.

  PMID: 20673547 BACKGROUND

• Valentine GW, Mason GF, Gomez R, Fasula M, Watzl J, Pittman B, Krystal JH, Sanacora G. The antidepressant effect of ketamine is not associated with changes in occipital amino acid neurotransmitter content as measured by [(1)H]-MRS. Psychiatry Res. 2011 Feb 28;191(2):122-7. doi: 10.1016/j.pscychresns.2010.10.009. Epub 2011 Jan 12.

  PMID: 21232924 BACKGROUND

• Zarate CA Jr, Brutsche NE, Ibrahim L, Franco-Chaves J, Diazgranados N, Cravchik A, Selter J, Marquardt CA, Liberty V, Luckenbaugh DA. Replication of ketamine's antidepressant efficacy in bipolar depression: a randomized controlled add-on trial. Biol Psychiatry. 2012 Jun 1;71(11):939-46. doi: 10.1016/j.biopsych.2011.12.010. Epub 2012 Jan 31.

  PMID: 22297150 BACKGROUND

• 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

• 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.

  PMID: 20679587 BACKGROUND

• Horn DI, Yu C, Steiner J, Buchmann J, Kaufmann J, Osoba A, Eckert U, Zierhut KC, Schiltz K, He H, Biswal B, Bogerts B, Walter M. Glutamatergic and resting-state functional connectivity correlates of severity in major depression - the role of pregenual anterior cingulate cortex and anterior insula. Front Syst Neurosci. 2010 Jul 15;4:33. doi: 10.3389/fnsys.2010.00033. eCollection 2010.

  PMID: 20700385 BACKGROUND

• 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 BACKGROUND

• Musazzi L, Treccani G, Mallei A, Popoli M. The action of antidepressants on the glutamate system: regulation of glutamate release and glutamate receptors. Biol Psychiatry. 2013 Jun 15;73(12):1180-8. doi: 10.1016/j.biopsych.2012.11.009. Epub 2012 Dec 28.

  PMID: 23273725 BACKGROUND

• Luykx JJ, Laban KG, van den Heuvel MP, Boks MP, Mandl RC, Kahn RS, Bakker SC. Region and state specific glutamate downregulation in major depressive disorder: a meta-analysis of (1)H-MRS findings. Neurosci Biobehav Rev. 2012 Jan;36(1):198-205. doi: 10.1016/j.neubiorev.2011.05.014. Epub 2011 Jun 6.

  PMID: 21672551 BACKGROUND

• Stone JM, Dietrich C, Edden R, Mehta MA, De Simoni S, Reed LJ, Krystal JH, Nutt D, Barker GJ. Ketamine effects on brain GABA and glutamate levels with 1H-MRS: relationship to ketamine-induced psychopathology. Mol Psychiatry. 2012 Jul;17(7):664-5. doi: 10.1038/mp.2011.171. Epub 2012 Jan 3. No abstract available.

  PMID: 22212598 BACKGROUND

• Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry. 2009 May 1;65(9):732-41. doi: 10.1016/j.biopsych.2008.11.029. Epub 2009 Jan 15.

  PMID: 19150053 BACKGROUND

• Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctot KL. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010 Mar 1;67(5):446-57. doi: 10.1016/j.biopsych.2009.09.033. Epub 2009 Dec 16.

  PMID: 20015486 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depression; Neuroinflammatory Diseases

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior; Nervous System Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Rodrigo Pérez-Esparza, MD

  National Institute of Neurology and Neurosurgery, Mexico

  PRINCIPAL INVESTIGATOR

• Jesús Ramírez-Bermúdez, MD, MSc

  National Institute of Neurology and Neurosurgery, Mexico

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rodrigo Pérez-Esparza, MD

CONTACT

56063822; dr.rodrigope@gmail.com

Jesús Ramírez-Bermúdez, MD, MSc

CONTACT

56063822; jesusramirezb@yahoo.com.mx

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Fourth-year Psychiatry Resident

Study Record Dates

• First Submitted: November 17, 2015
• First Posted: November 20, 2015
• Study Start: May 1, 2014
• Primary Completion: December 1, 2017
• Last Updated: September 21, 2016

Record last verified: 2016-09

Locations

ME (1)