Efficacy of Deep Anaesthesia With Isoflurane as a Fast-response Antidepressant Agent

Efficacy of Deep Anaesthesia With Isoflurane as a Fast-response Antidepressant Agent in Treatment Resistant Depression Patients : Proof of Concept

Patrocinadores

Patrocinador principal: University of Sao Paulo

Colaborador: Fundação de Amparo à Pesquisa do Estado de São Paulo

Fuente University of Sao Paulo
Resumen breve

In this study the investigators will submit patients with treatment resistant depression to deep anesthesia with isoflurane to get 15 minutes of cortical burst suppression on electroencephalogram, once a week for six weeks. The follow up will be for 6 months. The aim is to evaluate the change in depression severity during the entire period.

Descripción detallada

This study protocol will measure the efficacy of deep anesthesia, until burst suppression rate of 80% or more measured with Bi-spectral Index (BIS), with the volatile anesthetic Isoflurane. The investigators will select 30 subjects. The participants will be separated into 2 arms of 15 individuals. One arm called ISOAD will keep the oral treatment with antidepressants. The second arm, called ISO, will do a washout of any oral medications for depression. Both groups will go under six sessions, once per week, of deep anesthesia and will be followed up for 6 months to evaluate the survival of the antidepressant effect, if any effect happens. Before the anesthesia occurs, blood samples will be drawn to measure Brain-derived neurotrophic factor and investigators will apply depression rating scales such as MADRS and Hamilton - 17 , Young mania Scale, UKU scale for side effects, electroencephalogram will be recorder to be compared with the data shown on BIS. All the anesthesia procedure will be done with induction with propofol, fentanyl and muscular relaxant, to facilitate the tracheal intubation and compliance with the mechanical ventilator,based on body weight in standard dosages. Isoflurane will be set to 2,4% ( 2 cam) until Burst suppression rate >80% is achieve. Then the anesthesia will be maintained for 15 minutes, then the flow of anesthetic gas will be ended and the patient will be allowed to awake and discharged home when the anesthesiologist decide based on Aldrete Kroulik scale. After the 6th session the participant will return in one week to final evaluation. All the patients that shows improvement in depression scores will enter the phase 2 with one visit every 15 days for 2 months and then once a month until the 6th month. The non responders of the ISO group will start oral antidepressant sertraline to evaluate any potentialization effect of the intervention and be allocated in ISOPOT group. Those from ISOAD group (Isoflurane plus oral antidepressants) that did not respond to the intervention will be discontinued from the study and their data used in the study as non-responders. Those from ISOPOT group that did not improve their depression scores after 4 weeks will be discontinued from the study and the data computed as non-responders.

Estado general Not yet recruiting
Fecha de inicio December 2019
Fecha de Terminación December 2020
Fecha de finalización primaria September 2020
Fase Phase 2
Tipo de estudio Interventional
Resultado primario
Medida Periodo de tiempo
Reduction in Depression severity - MADRS Six days after the last session
Reduction in Depression - HDRS 17 Six days after the last session
Resultado secundario
Medida Periodo de tiempo
Udvalg for Kliniske Undersøgelser - side effects rating scale From 6th day after the first intervention up to week 24th
Change in Depression severity MADRS From 6th day after the intervention up to week 24th
Change in Depression severity HDRS17 From 6th day after the intervention up to week 24th
Magnitude MADRS From 6th day after the intervention up to week 24th
Magnitude HDRS 17 From 6th day after the intervention up to week 24th
Survival of the effect - HDRS 17 After the 6th session through 24th week
Survival of the effect - MADRS After the 6th session through 24th week
Enhance HDRS 17 After the 10th visit through the 24th week
Enhance MADRS After the 10th visit through the 24th week
Inscripción 30
Condición
Intervención

Tipo de intervención: Drug

Nombre de intervención: Isoflurane

Descripción: Deep anesthesia with isoflurane to achieve burst suppression pattern for more than 80% of the time for 15 minutes measured in electroencephalogram and Bi-Spectral Index

Tipo de intervención: Drug

Nombre de intervención: Sertraline Pill

Descripción: Patients that did not respond to Isoflurane treatment, will star on sertraline to evaluate any enhancement in antidepressant efficacy after pre-treatment with isoflurane

Etiqueta de grupo de brazo: ISOPOT

Elegibilidad

Criterios:

Inclusion Criteria:

- Patients with Treatment resistant depression on depressive state with or without psychiatric comorbidities for anxious features

- moderate to severe condition measured by Montgomery Asperger Depression Rating Scale and Hamilton Depression rating scale - 17

- be between 18 and 60 years old

- IF female, do not be pregnant and use a trustable contraceptive method

- can read and write in Portuguese language

- will to be in all the phases of the study

- have agreed with free will to participate

- classified as American Society of Anesthesiologists - Physical Status 1 or 2 by a certified anesthesiologist

- Suicide ideation measured by Montgomery Asperger Depression Rating Scale on item 10 less than 4

Exclusion Criteria:

- drug abusers in the last 6 months, except for nicotine

- use of benzodiazepines or lamotrigine less then 15 days from the first session

- family history of malignant hyperthermia Suicidal ideation on item 10 of Montgomery Asperger Depression Rating Scale more than 4

- Suicide attempt one month prior the study begins

Género: All

Edad mínima: 18 Years

Edad máxima: 60 Years

Voluntarios Saludables: No

Oficial general
Apellido Papel Afiliación
Ricardo Alberto Moreno, Phd Study Director Instituto de Psiquiatria do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
Contacto general

Apellido: Tiago Gil, MD

Teléfono: 5511983817707

Email: [email protected]

Ubicación
Instalaciones: Insitute of Psychiatry of the University of São Paulo
Ubicacion Paises

Brazil

Fecha de verificación

November 2019

Fiesta responsable

Tipo: Principal Investigator

Afiliación del investigador: University of Sao Paulo

Nombre completo del investigador: Ricardo Alberto Moreno, M.D., Ph.D.

Título del investigador: DIRECTOR: MOOD DISORDERS UNIT (GRUDA)

Palabras clave
Tiene acceso ampliado No
Condición Examinar
Número de brazos 3
Grupo de brazo

Etiqueta: ISO

Tipo: Experimental

Descripción: Patients not taking oral medications for depression. They will receive the study intervention consisting in general anesthesia with the volatile anesthetic gas Isoflurane until burst suppression is detected in electroencephalogram more than 80% of the time for 15 minutes.

Etiqueta: ISOAD

Tipo: Experimental

Descripción: Patients in treatment with oral medications for depression, will receive intervention consisting in general anesthesia with the volatile anesthetic gas Isoflurane until burst suppression is detected in electroencephalogram more than 80% of the time for 15 minutes

Etiqueta: ISOPOT

Tipo: Experimental

Descripción: Patients that where from ISO arm, that did not respond to intervention consisting in general anesthesia with the volatile anesthetic gas Isoflurane until burst suppression is detected in electroencephalogram more than 80% of the time for 15 minutes They will now, start taking sertraline as oral medication for depression to asset the enhancement of oral treatment after Isoflurane challenge.

Acrónimo ISORADAR
Información de diseño del estudio

Asignación: Randomized

Modelo de intervención: Parallel Assignment

Descripción del modelo de intervención: We will have two groups, one arm with oral antidepressants and other arm without oral antidepressants, no placebo, no control. Everyone receives the intervention. Those who respond to treatment, will be followed for 24 weeks, those who do not respond, if not in the oral antidepressant group, will star oral antidepressants and be followed for 24 weeks

Propósito primario: Treatment

Enmascaramiento: None (Open Label)

Fuente: ClinicalTrials.gov