Evaluation of Schemes of Administration of Intravenous Ketamine in Depression

NCT03742557 | Unknown Phase 3 DMC

• 1 other identifier: 74/18
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Mexico, prevalence reported for major depressive disorder (MDD) is of 7.2%. It is currently in the top 5 causes of disability worldwide. One third of patients will not achieve remission after two treatments, being classified as treatment-resistant. In a neurochemical level, evidence shows dysregulation of the excitatory neurotransmitter Glutamate in patients with MDD. Chronic stress has been related to this dysregulation. Ketamine, has shown to regulate glutamatergic neurotransmission, and specially promote the release and production of neurotrophic factors key in the causes of MDD inhibited by glutamate dysregulation), and allow restoration of areas affected. Clinical studies of ketamine in MDD have shown robust, durable , and rapid effects (during the first 4-24 hours), allowing a great opportunity for patients who do not achieve benefits from antidepressants or patients with suicidal ideation . These results have been reported in metaanalysis. To our knowledge, there are no studies using Magnetic Resonance Spectroscopy, in areas related to MDD, after a series of ketamine administrations, which we think may show changes after this chronic administration and explain its antidepressant properties. Goals: Provide clinical evidence of responseas well as a neurological basis or biomarker of response to a series of ketamine infusions.

Conditions

Treatment Resistant Depression

Keywords

Depression; Ketamine; Treatment-Resistant; Magnetic Resonance Spectroscopy

Outcome Measures

Primary Outcomes (4)

• Depression Severity Hamilton Depression Rating Scale

  Depression Severity (10 - 13 mild; 14-17 mild to moderate; \>17 moderate to severe). Higher values represent a worse severity, but not necessarily outcome.

  4, 24, 72 hours, weekly up to 12 weeks or until relapse (Change from baseline to each measure)

• Glutamate

  Glutamate levels in the pgACC basal and after the last intervention with ketamine or placebo

  Basal, 10 minutes during intervention, 24 hours after, 4 weeks after (Change from baseline to each measure)

• GABA

  GABA levels in the pgACC basal and after the last intervention with ketamine or placebo

  Basal, 10 minutes during intervention, 24 hours after, 4 weeks after (Change from baseline to each measure)

• Depression Severity Montgomery-Asberg Depression Rating Scale)

  Depression Severity (9-17 = mild, 18-34 = moderate, and ≥ 35 = severe)

  4, 24, 72 hours, weekly up to 12 weeks or until relapse (Change from baseline to each measure). Higher values represent a worse severity, but not necessarily outcome.

Study Arms (2)

Ketamine

ACTIVE COMPARATOR

Ketamine 50 MG/ML - at a dose of 0.5 mg/kg IV diluted in 100cc of saline solution 0.9% over 40 minutes. The intervention will be done twice weekly for 8 weeks.

Drug: Ketamine 50 MG/ML Injectable Solution, 0.5 mg/kg IV

Placebo

PLACEBO COMPARATOR

Saline solution 0.9% over 40 minutes. The intervention will be done twice weekly for 2 weeks, and then patients will receive intervention with ketamine as described above in the Active Comparator.

Drug: Ketamine 50 MG/ML Injectable Solution, 0.5 mg/kg IV

Interventions

Ketamine 50 MG/ML Injectable Solution, 0.5 mg/kg IV DRUG

Ketamine 0.5 mg/kg IV

Also known as: Ketalar, Anesket

Ketamine; Placebo

Eligibility Criteria

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

You may qualify if:

• Age: 18-65 years
• MDD diagnosis as provided by DSM-5 criteria
• TRD as defined by failure to achieve response to two consecutive antidepressant therapies at an adequate dose and duration

You may not qualify if:

• Comorbidity with other mental and neurological disorders (except generalized anxiety disorder)
• Substance use disorders at least 3 months prior to enrollment
• Evidence of structural abnormalities in basal MRI
• Pregnancy or lactation
• Hypersensitivity to ketamine
• Cardiac failure
• Personal history of psychosis
• First-degree relatives with history of psychosis
• Uncontrolled close-angle glaucoma
• Neurological disease (present)
• Uncontrolled Hypertension
• Contraindications for the realization of H1-MRS.

Sponsors & Collaborators

• National Institute of Neurology and Neurosurgery, Mexico: lead

Study Sites (1)

Instituto Nacional de Neurología y Neurocirugía (National Institute of Neurology and Neurosurgery)

Mexico City, Tlalpan, 14269, Mexico

RECRUITING

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  PMID: 27480494 RESULT

• Perez-Esparza R, Corona T, Ruiz-Garcia RG, Onate-Cadena N, de la Fuente-Sandoval C, Ramirez-Bermudez J. Time until relapse after augmentation with single-dose ketamine in treatment-resistant depression. Psychiatry Clin Neurosci. 2018 Aug;72(8):623. doi: 10.1111/pcn.12675. Epub 2018 Jun 19. No abstract available.

  PMID: 29744959 RESULT

• Perez-Esparza R. Ketamine for Treatment-Resistant Depression: a New Advocate. Rev Invest Clin. 2018;70(2):65-7. doi: 10.24875/RIC.18002501.

  PMID: 29718013 RESULT

• de la Fuente-Sandoval C, Reyes-Madrigal F, Mao X, Leon-Ortiz P, Rodriguez-Mayoral O, Jung-Cook H, Solis-Vivanco R, Graff-Guerrero A, Shungu DC. Prefrontal and Striatal Gamma-Aminobutyric Acid Levels and the Effect of Antipsychotic Treatment in First-Episode Psychosis Patients. Biol Psychiatry. 2018 Mar 15;83(6):475-483. doi: 10.1016/j.biopsych.2017.09.028. Epub 2017 Oct 10.

  PMID: 29132653 RESULT

• de la Fuente-Sandoval C. Potential Regional Differences in GABA Levels in Patients With Psychosis Compared With Control Subjects. Am J Psychiatry. 2016 Jul 1;173(7):734. doi: 10.1176/appi.ajp.2016.16030261. No abstract available.

  PMID: 27363558 RESULT

• de la Fuente-Sandoval C, Reyes-Madrigal F, Mao X, Leon-Ortiz P, Rodriguez-Mayoral O, Solis-Vivanco R, Favila R, Graff-Guerrero A, Shungu DC. Cortico-Striatal GABAergic and Glutamatergic Dysregulations in Subjects at Ultra-High Risk for Psychosis Investigated with Proton Magnetic Resonance Spectroscopy. Int J Neuropsychopharmacol. 2015 Sep 12;19(3):pyv105. doi: 10.1093/ijnp/pyv105.

  PMID: 26364273 RESULT

• Singh I, Morgan C, Curran V, Nutt D, Schlag A, McShane R. Ketamine treatment for depression: opportunities for clinical innovation and ethical foresight. Lancet Psychiatry. 2017 May;4(5):419-426. doi: 10.1016/S2215-0366(17)30102-5. Epub 2017 Apr 5.

  PMID: 28395988 RESULT

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depression

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

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

Study Officials

• Rodrigo Pérez-Esparza, M.D., M.Sc.

  National Institute of Neurology and Neurosurgery

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rodrigo Pérez-Esparza, M.D., M.Sc.

CONTACT

+5256063822; dr.rodrigope@gmail.com

Camilo de la Fuente-Sandoval, M.D., Ph.D.

CONTACT

+56063822; fcamilo@unam.mx

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Sciences Investigator

Model Details: A double-blind randomized clinical trial (initially) will be performed, followed by an open-label trial.

Study Record Dates

• First Submitted: November 8, 2018
• First Posted: November 15, 2018
• Study Start: October 1, 2018
• Primary Completion: January 1, 2020
• Study Completion: January 1, 2020
• Last Updated: September 10, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)