Clinical Trial of the Use of Ketamine in Treatment Resistant Depression

Depressive Disorder, Treatment-Resistant Clinical Trial

Official title:

Clinical Trial of the Use of Ketamine in Treatment Resistant Depression

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02610712
• Other study ID #: 63/13
• Status: Recruiting
• Phase: Phase 4
• First received: November 17, 2015
• Last updated: September 20, 2016
• Start date: May 2014

Study information

• Verified date: September 2016
• Source: National Institute of Neurology and Neurosurgery, Mexico
• Contact: Rodrigo Pérez-Esparza, MD
• Phone: 56063822
• Email: dr.rodrigope[@]gmail.com
• Is FDA regulated: No
• Health authority: Mexico: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Description:

The purpose of this study is to determine the efficacy of the use of intravenous low-dose ketamine (0.5 mg/kg) in the treatment of treatment-resistant depression (TRD), as well as the changes in Glutamate neurotransmission measured by Magnetic Resonance Imaging Spectroscopy and inflammatory serum markers (IL-6, TNF-alpha).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Treatment-Resistant

Intervention

Drug:
• Ketamine

Locations

Country	Name	City	State
Mexico	National Institute of Neurology and Neurosurgery	Mexico City	Distrito Federal

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Neurology and Neurosurgery, Mexico

Country where clinical trial is conducted

Mexico, 

References & 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. — View Citation

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. — View Citation

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. — View Citation

Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctôt 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. — View Citation

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. pii: 33. doi: 10.3389/fnsys.2010.00033. eCollection 2010. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hamilton Depression Rating Scale (HDRS) Score		Change from baseline HDRS Score at 24 hours	No
Secondary	Glutamate concentrations in the pregenual cingulate cortex (pgACC)	Glutamate concentrations in the pregenual cingulate cortex measured by Magnetic Resonance Spectroscopy	Change from baseline Glutamate concentrations in the pgACC at 24 hours	No
Secondary	Interleukin-1 (IL-1) and Tumoral Necrosis Factor-alpha (TNF-alpha) serum concentrations	Interleukin-1 and Tumoral Necrosis Factor-alpha concentrations in serum measured by ELISA	Change from baseline IL-1 and TNF-alpha serum concentrations from baseline at 24 hours	No