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

Primary Purpose

Depressive Disorder, Major, Treatment Resistant Depression, Depressive Episode

Status
Unknown status
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
Isoflurane
Sertraline Pill
Sponsored by
University of Sao Paulo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Depressive Disorder, Major focused on measuring Isoflurane, Anesthesia, Treatment resistant depression, Deep anesthesia, Burst suppression, Depressive episode

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Insitute of Psychiatry of the University of São Paulo

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

ISO

ISOAD

ISOPOT

Arm Description

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.

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

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.

Outcomes

Primary Outcome Measures

Reduction in Depression severity - MADRS
Any reduction in Montgomery Asperger Depression Rating Scale ( 0 to 60 , lower score means less depression severity)
Reduction in Depression - HDRS 17
Any reduction in Hamilton Depression rating scale 17 ( 0 to 49, lower score means less depression severity

Secondary Outcome Measures

Udvalg for Kliniske Undersøgelser - side effects rating scale
Development and tolerability of collateral effects using the Udvalg for Kliniske Undersøgelser - side effects rating scale ( 0 to 43 - lower score means less side effects)
Change in Depression severity MADRS
Any change in Montgomery Asperger depression ratings scale ( 0 to 60 , lower score means less depression severity)
Change in Depression severity HDRS17
Any change in Hamilton depression ratings scale 17 ( 0 to 49, lower score means less depression severity)
Magnitude MADRS
The amount of the reduction, if any, in Montgomery Asperger Depression Rating Scale ( 0 to 60 , lower score means less depression severity)
Magnitude HDRS 17
The amount of the reduction, if any, in Hamilton Depression rating scale 17 ( 0 to 49, lower score means less depression severity)
Survival of the effect - HDRS 17
For how long the Hamilton Depression rating scale 17 remains below the initial value (lower value means less depression) in each participant that had variation in this scale
Survival of the effect - MADRS
For how long the Montgomery Asperger Depression Rating Scale remains below the initial value (lower value means less depression) in each participant that had variation in this scale
Enhance HDRS 17
The magnitude, if any, of the change in Hamilton Depression rating scale 17 measured in patients that did not achieve any primary outcome in the first phase of the study after started sertraline as oral antidepressant.
Enhance MADRS
The magnitude, if any, of the change in Montgomery Asperger Depression Rating Scale measured in patients that did not achieve any primary outcome in the first phase of the study after started sertraline as oral antidepressant.

Full Information

First Posted
November 6, 2019
Last Updated
November 18, 2019
Sponsor
University of Sao Paulo
Collaborators
Fundação de Amparo à Pesquisa do Estado de São Paulo
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1. Study Identification

Unique Protocol Identification Number
NCT04171193
Brief Title
Efficacy of Deep Anaesthesia With Isoflurane as a Fast-response Antidepressant Agent
Acronym
ISORADAR
Official Title
Efficacy of Deep Anaesthesia With Isoflurane as a Fast-response Antidepressant Agent in Treatment Resistant Depression Patients : Proof of Concept
Study Type
Interventional

2. Study Status

Record Verification Date
November 2019
Overall Recruitment Status
Unknown status
Study Start Date
December 2019 (Anticipated)
Primary Completion Date
September 2020 (Anticipated)
Study Completion Date
December 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Sao Paulo
Collaborators
Fundação de Amparo à Pesquisa do Estado de São Paulo

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depressive Disorder, Major, Treatment Resistant Depression, Depressive Episode
Keywords
Isoflurane, Anesthesia, Treatment resistant depression, Deep anesthesia, Burst suppression, Depressive episode

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
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
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
ISO
Arm Type
Experimental
Arm Description
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.
Arm Title
ISOAD
Arm Type
Experimental
Arm Description
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
Arm Title
ISOPOT
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Isoflurane
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Sertraline Pill
Intervention Description
Patients that did not respond to Isoflurane treatment, will star on sertraline to evaluate any enhancement in antidepressant efficacy after pre-treatment with isoflurane
Primary Outcome Measure Information:
Title
Reduction in Depression severity - MADRS
Description
Any reduction in Montgomery Asperger Depression Rating Scale ( 0 to 60 , lower score means less depression severity)
Time Frame
Six days after the last session
Title
Reduction in Depression - HDRS 17
Description
Any reduction in Hamilton Depression rating scale 17 ( 0 to 49, lower score means less depression severity
Time Frame
Six days after the last session
Secondary Outcome Measure Information:
Title
Udvalg for Kliniske Undersøgelser - side effects rating scale
Description
Development and tolerability of collateral effects using the Udvalg for Kliniske Undersøgelser - side effects rating scale ( 0 to 43 - lower score means less side effects)
Time Frame
From 6th day after the first intervention up to week 24th
Title
Change in Depression severity MADRS
Description
Any change in Montgomery Asperger depression ratings scale ( 0 to 60 , lower score means less depression severity)
Time Frame
From 6th day after the intervention up to week 24th
Title
Change in Depression severity HDRS17
Description
Any change in Hamilton depression ratings scale 17 ( 0 to 49, lower score means less depression severity)
Time Frame
From 6th day after the intervention up to week 24th
Title
Magnitude MADRS
Description
The amount of the reduction, if any, in Montgomery Asperger Depression Rating Scale ( 0 to 60 , lower score means less depression severity)
Time Frame
From 6th day after the intervention up to week 24th
Title
Magnitude HDRS 17
Description
The amount of the reduction, if any, in Hamilton Depression rating scale 17 ( 0 to 49, lower score means less depression severity)
Time Frame
From 6th day after the intervention up to week 24th
Title
Survival of the effect - HDRS 17
Description
For how long the Hamilton Depression rating scale 17 remains below the initial value (lower value means less depression) in each participant that had variation in this scale
Time Frame
After the 6th session through 24th week
Title
Survival of the effect - MADRS
Description
For how long the Montgomery Asperger Depression Rating Scale remains below the initial value (lower value means less depression) in each participant that had variation in this scale
Time Frame
After the 6th session through 24th week
Title
Enhance HDRS 17
Description
The magnitude, if any, of the change in Hamilton Depression rating scale 17 measured in patients that did not achieve any primary outcome in the first phase of the study after started sertraline as oral antidepressant.
Time Frame
After the 10th visit through the 24th week
Title
Enhance MADRS
Description
The magnitude, if any, of the change in Montgomery Asperger Depression Rating Scale measured in patients that did not achieve any primary outcome in the first phase of the study after started sertraline as oral antidepressant.
Time Frame
After the 10th visit through the 24th week

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tiago Gil, MD
Phone
5511983817707
Email
Tiagogil@gmail.colm
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ricardo Alberto Moreno, Phd
Organizational Affiliation
Instituto de Psiquiatria do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
Official's Role
Study Director
Facility Information:
Facility Name
Insitute of Psychiatry of the University of São Paulo
City
São Paulo
Country
Brazil

12. IPD Sharing Statement

Learn more about this trial

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

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