Impact of Closely Grouped, Iterative Exposures to Suxamethonium During ECT on the Sensitization to NMBA and the Development of Protective Antibodies (SismoSens)

April 4, 2022 updated by: Assistance Publique - Hôpitaux de Paris

Impact of Closely Grouped, Iterative Exposures to Suxamethonium During Electroconvulsive Therapy (ECT) on the Sensitization to Neuro-Muscular Blocking Agents (NMBA) and the Development of Protective Antibodies

Acute per-anesthetic hypersensitivity reaction (HSA-PA) is a rapidly occurring systemic reaction following injection of a drug during anesthesia (mortality between 3 and 9%). The substances responsible for these reactions in France are Neuro-Muscular Blocking Agents (NMBA) in 60% of cases. The main mechanism mentioned is an immediate systemic hypersensitivity immune reaction (anaphylaxis). The mechanism of immunization to NMBA is not yet understood.

Electroconvulsive therapy (ECT) is a long-standing therapeutic approach still widely used today, for its high efficiency, particularly in depressive syndromes resistant to antidepressants. It has an efficacy comparable (or even superior) to pharmacological treatments and improves the mortality associated with this disease. Treatment with iterative ECT sessions includes an attack phase with an average of 12 sessions over 4 weeks, with secondary spacing of sessions before switching to antidepressant treatment. These sessions are carried out in the operating room under general anesthesia, thanks to a hypnotic and a NMBA, suxamethonium, as recently recommended by the French Anesthesiology Society in 2020.

ECT therefore represent an interesting model of iterative exposure of a relatively homogeneous population to a single highly sensitizing substance, which could make it possible to study the evolution of sensitization as a function of various factors, in particular cumulative exposure, for which no data is currently available.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Acute per-anesthetic hypersensitivity reaction (HSA-PA) is a rapidly occurring systemic reaction following injection of a drug during anesthesia (mortality between 3 and 9%). The substances responsible for these reactions are different types of Neuro-Muscular Blocking Agents (NMBA) in 60% of cases. The main mechanism mentioned is an immediate systemic hypersensitivity immune reaction (anaphylaxis). Anaphylactic reactions are classically described as IgE-dependent, triggered by the allergen which, by bridging specific IgE antibodies on the surface of mast cells and basophils, induces a massive release, in particular of histamine, which is responsible for the symptoms. Other immunological mechanisms, in particular by specific IgGs, have been described. The mechanism of immunization to Neuro-Muscular Blocking Agents (NMBA) is not yet understood. The quaternary ammonium group (AQ) is the common epitope of NMBA recognized by IgE. Due to the absence of previous exposure to NMBA reported in 50% of patients with HSA-PA to NMBA, other substances carrying substituted AQ ions are suspected of inducing cross-sensitization, such as household cleaners, cosmetics or drug (pholcodine). However, the sensitizing role of NMBA themselves is not established, and no study has analyzed iterative exposure to Neuro-Muscular Blocking Agents (NMBA) as a sensitizing factor.

Electroconvulsive therapy (ECT) is a long-standing therapeutic approach still widely used today, for its high efficiency, particularly in depressive syndromes resistant to antidepressants. It has an efficacy comparable (or even superior) to pharmacological treatments and improves the mortality associated with this disease. Treatment with iterative ECT sessions includes an attack phase with an average of 12 sessions over 4 weeks, with secondary spacing of sessions before switching to antidepressant treatment. These sessions are carried out in the operating room under general anesthesia, thanks to a hypnotic and a NMBA, suxamethonium, as recently recommended by the French Anesthesiology Society in 2020.

ECT therefore represent an interesting model of iterative exposure of a relatively homogeneous population to a single highly sensitizing substance, which could make it possible to study the evolution of sensitization as a function of various factors, in particular cumulative exposure, for which no data is currently available.

A single patient group is planned in this study, consisting of patients with a medical indication for ECT for psychiatric pathologies resistant to medical treatment (depression, mania, hallucinatory episode in particular). The study will take place in two parts: a preliminary phase "phase P" in 10 patients (with previous exposure to ECT) and a "phase E" study phase in 60 patients. For phase E, only patients with first-time access to ECT or without ECT in the previous ten years will be eligible.

Study Type

Observational

Enrollment (Anticipated)

70

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Paris, France, 75012
        • Recruiting
        • Saint-Antoine Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients requiring ECT for psychiatric pathologies that are resistant to medical treatments (particularly depression, mania, hallucinations).

  • Phase P (pilot): 10 patients to be included in 1 month with a unique dose. The analysis will be done the following month. The objective is to ennsure the number of patients to include in phase E.
  • Phase E (study): 60 patients to be included in 12 months (follow-up care until 6 months) with 5 biological samples: before the first exposure to ECT (S0), after 2 weeks (S2), at 4 weeks (S4), between 6 - 14 weeks (S10) and at 6 months (M6). Only patients having exposed to ECT in the past 10 years will be included in this trial. Grouped analysis shall be done at the end of the study.

Description

Inclusion Criteria:

  • Patient requiring iterative exposure to ECT as part of their psychiatric pathology in one of the investigator center
  • Patient who has not had ECT in the last 10 years for the phase E group, regardless of their previous ECT exposure for the phase P group
  • Patient who has been informed and has signed the consent form

Exclusion Criteria:

  • Absence of written informed consent
  • Allergies identified specifically to Neuro-Muscular Blocking Agents (NMBA)
  • Patient under tutelage, curatorship or judicial protection
  • Patient without social security
  • Contraindication to ECT : intracranial hypertension, intracranial lesions without intracranial hypertension, recent episode of cerebral hemorrhage, recent myocardial infarction or embologenic disease, presence of aneurysms or vascular malformations at risk of hemorrhage, retinal detachment, pheochromocytoma, history of ineffective treatment with ECT having had serious side effects, taking anticoagulant treatments

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Exposure to suxamethonium during ECT
A single group is planned in this study, consisting of patients with a medical indication for ECT for psychiatric pathologies which are resistant to medical treatment (depression, mania, hallucinatory episode in particular).
Other: Iterative exposure to suxamethonium during ECT sessions

The study is divided into 2 phases: phase P and phase E. Phase P: 10 patients to be included in 1 month with a unique dose of suxamethonium during one session of ECT. One blood sample will be taken from patients before their index ECT session. The objective is to evaluate the feasibility of antibody detection relative to the main objective of the study, to ensure the number of patients to include in phase E (analysis in the following month). Depending on the frequency of antibodies detected, particularly IgG4, the number of patients required for phase E will be revised. If no antibodies are detected, the study will be discontinued.

Phase E: 60 patients to be included in 12 months with 5 blood samples: before the first session of ECT (S0), at 2 weeks (S2), at 4 weeks (S4), between 6 - 14 weeks (preferably at S10) and at 6 months (M6). Only first-time patients or those not having been exposed to ECT in the past 10 years will be included in this phase.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate the development of specific antibodies against suxamethonium (type IgG4 anti-suxamethonium) after iterative exposure to ECT at 10 weeks.
Time Frame: 10 weeks
Development of specific antibodies against suxamethonium
10 weeks
Incidence of protective antibodies against suxamethonium assessed by the presence of specific anti-suxamethonium IgG4 antibodies (via ImmunoCAP method) following iterative exposure to ECT after 10 weeks.
Time Frame: 10 weeks
Incidence of protective antibodies against suxamethonium
10 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate the development of specific IgE antibodies against quaternary ammoniums and suxamethonium after iterative exposure to ECT at 2 weeks.
Time Frame: 2 weeks
Development of specific IgE antibodies
2 weeks
Evaluate the development of specific IgE antibodies against quaternary ammoniums and suxamethonium after iterative exposure to ECT at 4 weeks.
Time Frame: 4 weeks
Development of specific IgE antibodies
4 weeks
Evaluate the development of specific IgE antibodies against quaternary ammoniums and suxamethonium after iterative exposure to ECT at 10 weeks.
Time Frame: 10 weeks
Development of specific IgE antibodies
10 weeks
Evaluate the development of specific IgG antibodies against quaternary ammoniums and suxamethonium after iterative exposure to ECT at 2 weeks.
Time Frame: 2 weeks
Development of specific IgG antibodies
2 weeks
Evaluate the development of specific IgG antibodies against quaternary ammoniums and suxamethonium after iterative exposure to ECT at 4 weeks.
Time Frame: 4 weeks
Development of specific IgG antibodies
4 weeks
Evaluate the development of specific IgG antibodies against quaternary ammoniums and suxamethonium after iterative exposure to ECT at 10 weeks.
Time Frame: 10 weeks
Development of specific IgG antibodies
10 weeks
Evaluate the development of specific IgG4 antibodies against quaternary ammoniums and suxamethonium after iterative exposure to ECT at 2 weeks.
Time Frame: 2 weeks
Development of specific IgG4 antibodies
2 weeks
Evaluate the development of specific IgG4 antibodies against quaternary ammoniums and suxamethonium after iterative exposure to ECT at 4 weeks.
Time Frame: 4 weeks
Development of specific IgG4 antibodies
4 weeks
Evaluate the development of specific IgG4 antibodies against quaternary ammoniums and suxamethonium after iterative exposure to ECT at 10 weeks.
Time Frame: 10 weeks
Development of specific IgG4 antibodies
10 weeks
Evaluate the evolution of anti-suxamethonium IgE/IgG4 ratio, described as an evaluation factor during desensitization procedures before exposure to ECT at 2 weeks.
Time Frame: 2 weeks
Evolution of anti-suxamethonium IgE/IgG4 ratio
2 weeks
Evaluate the evolution of anti-suxamethonium IgE/IgG4 ratio, described as an evaluation factor during desensitization procedures before exposure to ECT at 4 weeks.
Time Frame: 4 weeks
Evolution of anti-suxamethonium IgE/IgG4 ratio
4 weeks
Evaluate the evolution of anti-suxamethonium IgE/IgG4 ratio, described as an evaluation factor during desensitization procedures before exposure to ECT at 10 weeks.
Time Frame: 10 weeks
Evolution of anti-suxamethonium IgE/IgG4 ratio
10 weeks
Evaluate the evolution of anti-quaternary ammoniums IgE/IgG4 ratio, described as an evaluation factor during desensitization procedures before exposure to ECT at 2 weeks.
Time Frame: 2 weeks
Evolution of anti-quaternary ammoniums IgE/IgG4 ratio
2 weeks
Evaluate the evolution of anti-quaternary ammoniums IgE/IgG4 ratio, described as an evaluation factor during desensitization procedures before exposure to ECT at 4 weeks.
Time Frame: 4 weeks
Evolution of anti-quaternary ammoniums IgE/IgG4 ratio
4 weeks
Evaluate the evolution of anti-quaternary ammoniums IgE/IgG4 ratio, described as an evaluation factor during desensitization procedures before exposure to ECT at 10 weeks.
Time Frame: 10 weeks
Evolution of anti-quaternary ammoniums IgE/IgG4 ratio
10 weeks
Evaluate the evolution of anti-rocuronium IgE/IgG4 ratio, described as an evaluation factor during desensitization procedures before exposure to ECT at 2 weeks.
Time Frame: 2 weeks
Evolution of anti-rocuronium IgE/IgG4 ratio
2 weeks
Evaluate the evolution of anti-rocuronium IgE/IgG4 ratio, described as an evaluation factor during desensitization procedures before exposure to ECT at 4 weeks.
Time Frame: 4 weeks
Evolution of anti-rocuronium IgE/IgG4 ratioIgE/IgG4 ratio
4 weeks
Evaluate the evolution of anti-rocuronium IgE/IgG4 ratio, described as an evaluation factor during desensitization procedures before exposure to ECT at 10 weeks.
Time Frame: 10 weeks
Evolution of anti-rocuronium IgE/IgG4 ratio
10 weeks
Evaluate the evolution of polarization of memory T cells before and after iterative exposure to ECT at 10 weeks via flow cytometry after re-stimulation with NMBA.
Time Frame: 10 weeks
Evolution of polarization of memory T cells
10 weeks
Evaluate circulating concentrations of tolerogenic factors (IL-10, IL-4, TGF-beta) before the first exposure to ECT.
Time Frame: Week 0
Evaluate circulating concentrations of tolerogenic factors
Week 0
Evaluate circulating concentrations of tolerogenic factors (IL-10, IL-4, TGF-beta) at 10 weeks.
Time Frame: 10 weeks
Evaluate circulating concentrations of tolerogenic factors
10 weeks
Evaluate whether iterative exposure induces cross-reactivity against rocuronium by quantitative analysis of anti-rocuronium IgE.
Time Frame: 18 months
Cross-reactivity against rocuronium by quantitative analysis of anti-rocuronium IgE.
18 months
Evaluate whether iterative exposure induces cross-reactivity against rocuronium by quantitative analysis of anti-rocuronium IgG.
Time Frame: 18 months
Cross-reactivity against rocuronium by quantitative analysis of anti-rocuronium IgG.
18 months
Evaluate the persistence of antibodies (IgE and IgG4 against quaternary ammoniums and suxamethonium) detected at 10 weeks since the last exposure to ECT.
Time Frame: 10 weeks
Persistence of antibodies detected at 10 weeks
10 weeks
Evaluate the persistence of antibodies (IgE and IgG4 against quaternary ammoniums and suxamethonium) detected at 6 months since the last exposure to ECT.
Time Frame: 6 months
Persistence of antibodies detected at 6 months
6 months
Describe the antibody profile before exposure to NMBA, and the potential link with previous drug exposures in the previous year of antidepressant, mood stabilizers and anxiolytics.
Time Frame: 18 months
Antibody profile before exposure to NMBA and the potential link with previous drug exposures in the previous year
18 months
Evaluate the influence of hormonal changes induced by ECT on immunization.
Time Frame: 18 months
Influence of hormonal changes on immunization
18 months
Incidence of specific IgE antibodies against quaternary ammonium, suxamethonium and rocuronium at 2 weeks.
Time Frame: 2 weeks
Incidence of specific IgE antibodies against quaternary ammonium suxamethonium and rocuronium (via ImmunoCAP and ELISA).
2 weeks
Incidence of specific IgE antibodies against quaternary ammonium, suxamethonium and rocuronium at 4 weeks.
Time Frame: 4 weeks
Incidence of specific IgE antibodies against quaternary ammonium suxamethonium and rocuronium (via ImmunoCAP and ELISA).
4 weeks
Incidence of specific IgE antibodies against quaternary ammonium, suxamethonium and rocuronium at 10 weeks.
Time Frame: 10 weeks
Incidence of specific IgE antibodies against quaternary ammonium suxamethonium and rocuronium (via ImmunoCAP and ELISA).
10 weeks
Incidence of specific IgE antibodies against quaternary ammonium, suxamethonium and rocuronium at 6 months.
Time Frame: 6 months
Incidence of specific IgE antibodies against quaternary ammonium suxamethonium and rocuronium (via ImmunoCAP and ELISA).
6 months
Incidence of specific IgG against quaternary ammonium, suxamethonium and rocuronium at 2 weeks.
Time Frame: 2 weeks
Incidence of specific IgG antibodies against quaternary ammonium suxamethonium and rocuronium (via ImmunoCAP and ELISA).
2 weeks
Incidence of specific IgG against quaternary ammonium, suxamethonium and rocuronium at 4 weeks.
Time Frame: 4 weeks
Incidence of specific IgG antibodies against quaternary ammonium suxamethonium and rocuronium (via ImmunoCAP and ELISA).
4 weeks
Incidence of specific IgG against quaternary ammonium, suxamethonium and rocuronium at 10 weeks.
Time Frame: 10 weeks
Incidence of specific IgG antibodies against quaternary ammonium suxamethonium and rocuronium (via ImmunoCAP and ELISA).
10 weeks
Incidence of specific IgG against quaternary ammonium, suxamethonium and rocuronium 6 months.
Time Frame: 6 months
Incidence of specific IgG antibodies against quaternary ammonium suxamethonium and rocuronium (via ImmunoCAP and ELISA).
6 months
Incidence of specific IgG4 against quaternary ammonium, suxamethonium and rocuronium at 2 weeks.
Time Frame: 2 weeks
Incidence of specific IgG4 antibodies against quaternary ammonium suxamethonium and rocuronium (via ImmunoCAP and ELISA).
2 weeks
Incidence of specific IgG4 against quaternary ammonium, suxamethonium and rocuronium at 4 weeks.
Time Frame: 4 weeks
Incidence of specific IgG4 antibodies against quaternary ammonium suxamethonium and rocuronium (via ImmunoCAP and ELISA).
4 weeks
Incidence of specific IgG4 against quaternary ammonium, suxamethonium and rocuronium at 10 weeks.
Time Frame: 10 weeks
Incidence of specific IgG4 antibodies against quaternary ammonium suxamethonium and rocuronium (via ImmunoCAP and ELISA).
10 weeks
Incidence of specific IgG4 against quaternary ammonium, suxamethonium and rocuronium at 6 months.
Time Frame: 6 months
Incidence of specific IgG4 antibodies against quaternary ammonium suxamethonium and rocuronium (via ImmunoCAP and ELISA).
6 months
Levels of specific IgE antibodies against quaternary ammonium, suxamethonium and rocuronium before the ECT session.
Time Frame: 18 months
Levels of specific IgE antibodies
18 months
Levels of specific IgG antibodies against quaternary ammonium, suxamethonium and rocuronium before the ECT session.
Time Frame: 18 months
Levels of specific IgG antibodies
18 months
Levels of specific IgG4 antibodies against quaternary ammonium, suxamethonium and rocuronium before the ECT session.
Time Frame: 18 months
Levels of specific IgG4 antibodies
18 months
Cytokine profile, particularly pro-tolerogenic, and development of Tregs lymphocytes.
Time Frame: 18 months
Profile of cyrokine
18 months
Risk factors: number of ECT sessions, exposure to pholcodine before or during the study, occupational exposure to quaternary ammoniums (hairdressers, cleaning agents, beauticians).
Time Frame: 18 months
Risk factors
18 months
Exposures of the previous year to antidepressant, mood stabilizers and anxiolytics.
Time Frame: 18 months
Previous exposure to antidepressant, mood stabilizers and anxiolytics
18 months
Assay of ACTH, cortisol at week 0.
Time Frame: Week 0
Assay of hormones
Week 0
Assay of ACTH, cortisol at week 10.
Time Frame: Week 10
Assay of hormones
Week 10

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Aurélie Gouel, APHP

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

January 27, 2022

Primary Completion (ANTICIPATED)

September 1, 2023

Study Completion (ANTICIPATED)

September 1, 2023

Study Registration Dates

First Submitted

January 14, 2022

First Submitted That Met QC Criteria

January 14, 2022

First Posted (ACTUAL)

January 27, 2022

Study Record Updates

Last Update Posted (ACTUAL)

April 12, 2022

Last Update Submitted That Met QC Criteria

April 4, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APHP210659

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe