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DepressionSismoSensNCT05210062

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

An observational study of Depression and Mania, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Depression, Mania, Hallucinations
What is being tested?
Iterative exposure to suxamethonium during ECT sessions
How many people
70 participants
Where
1 siteFrance
Study dates
27 Jan 2022to Sep 2023
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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.

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

France1 site, 1 recruiting
  • Saint-Antoine Hospital

    Paris, 75012

    Florian FERRERI, 01 49 28 26 35, florian.ferreri@aphp.fr

    Recruiting

Other trials in France

About this study

Official title: 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.

Read the 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.

Being tested
Iterative exposure to suxamethonium during ECT sessions
Keywords
Electroconvulsive therapy, Depressive disorders, Sensitization, Protective antibodies, Neuro-Muscular Blocking Agents (NMBA), Suxamethonium
Medical subject headings
Depression, Mania, Hallucinations, Depressive Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Iterative exposure to suxamethonium during ECT sessionsOther

    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.

Study groups in NCT05210062
Study groupRoleWhat they receive
Exposure to suxamethonium during ECTA 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).
Receives: Other: Iterative exposure to suxamethonium during ECT sessions

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Evaluate the development of specific antibodies against suxamethonium (type IgG4 anti-suxamethonium) after iterative exposure to ECT at 10 weeks.

    Development of specific antibodies against suxamethonium

    Measured: 10 weeks

  2. 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.

    Incidence of protective antibodies against suxamethonium

    Measured: 10 weeks

Secondary outcomes (47)
  1. Evaluate the development of specific IgE antibodies against quaternary ammoniums and suxamethonium after iterative exposure to ECT at 2 weeks.

    Development of specific IgE antibodies

    Measured: 2 weeks

  2. Evaluate the development of specific IgE antibodies against quaternary ammoniums and suxamethonium after iterative exposure to ECT at 4 weeks.

    Development of specific IgE antibodies

    Measured: 4 weeks

  3. Evaluate the development of specific IgE antibodies against quaternary ammoniums and suxamethonium after iterative exposure to ECT at 10 weeks.

    Development of specific IgE antibodies

    Measured: 10 weeks

  4. Evaluate the development of specific IgG antibodies against quaternary ammoniums and suxamethonium after iterative exposure to ECT at 2 weeks.

    Development of specific IgG antibodies

    Measured: 2 weeks

  5. Evaluate the development of specific IgG antibodies against quaternary ammoniums and suxamethonium after iterative exposure to ECT at 4 weeks.

    Development of specific IgG antibodies

    Measured: 4 weeks

  6. Evaluate the development of specific IgG antibodies against quaternary ammoniums and suxamethonium after iterative exposure to ECT at 10 weeks.

    Development of specific IgG antibodies

    Measured: 10 weeks

  7. Evaluate the development of specific IgG4 antibodies against quaternary ammoniums and suxamethonium after iterative exposure to ECT at 2 weeks.

    Development of specific IgG4 antibodies

    Measured: 2 weeks

  8. Evaluate the development of specific IgG4 antibodies against quaternary ammoniums and suxamethonium after iterative exposure to ECT at 4 weeks.

    Development of specific IgG4 antibodies

    Measured: 4 weeks

  9. Evaluate the development of specific IgG4 antibodies against quaternary ammoniums and suxamethonium after iterative exposure to ECT at 10 weeks.

    Development of specific IgG4 antibodies

    Measured: 10 weeks

  10. Evaluate the evolution of anti-suxamethonium IgE/IgG4 ratio, described as an evaluation factor during desensitization procedures before exposure to ECT at 2 weeks.

    Evolution of anti-suxamethonium IgE/IgG4 ratio

    Measured: 2 weeks

  11. Evaluate the evolution of anti-suxamethonium IgE/IgG4 ratio, described as an evaluation factor during desensitization procedures before exposure to ECT at 4 weeks.

    Evolution of anti-suxamethonium IgE/IgG4 ratio

    Measured: 4 weeks

  12. Evaluate the evolution of anti-suxamethonium IgE/IgG4 ratio, described as an evaluation factor during desensitization procedures before exposure to ECT at 10 weeks.

    Evolution of anti-suxamethonium IgE/IgG4 ratio

    Measured: 10 weeks

  13. 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.

    Evolution of anti-quaternary ammoniums IgE/IgG4 ratio

    Measured: 2 weeks

  14. 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.

    Evolution of anti-quaternary ammoniums IgE/IgG4 ratio

    Measured: 4 weeks

  15. 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.

    Evolution of anti-quaternary ammoniums IgE/IgG4 ratio

    Measured: 10 weeks

  16. Evaluate the evolution of anti-rocuronium IgE/IgG4 ratio, described as an evaluation factor during desensitization procedures before exposure to ECT at 2 weeks.

    Evolution of anti-rocuronium IgE/IgG4 ratio

    Measured: 2 weeks

  17. Evaluate the evolution of anti-rocuronium IgE/IgG4 ratio, described as an evaluation factor during desensitization procedures before exposure to ECT at 4 weeks.

    Evolution of anti-rocuronium IgE/IgG4 ratioIgE/IgG4 ratio

    Measured: 4 weeks

  18. Evaluate the evolution of anti-rocuronium IgE/IgG4 ratio, described as an evaluation factor during desensitization procedures before exposure to ECT at 10 weeks.

    Evolution of anti-rocuronium IgE/IgG4 ratio

    Measured: 10 weeks

  19. 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.

    Evolution of polarization of memory T cells

    Measured: 10 weeks

  20. Evaluate circulating concentrations of tolerogenic factors (IL-10, IL-4, TGF-beta) before the first exposure to ECT.

    Evaluate circulating concentrations of tolerogenic factors

    Measured: Week 0

  21. Evaluate circulating concentrations of tolerogenic factors (IL-10, IL-4, TGF-beta) at 10 weeks.

    Evaluate circulating concentrations of tolerogenic factors

    Measured: 10 weeks

  22. Evaluate whether iterative exposure induces cross-reactivity against rocuronium by quantitative analysis of anti-rocuronium IgE.

    Cross-reactivity against rocuronium by quantitative analysis of anti-rocuronium IgE.

    Measured: 18 months

  23. Evaluate whether iterative exposure induces cross-reactivity against rocuronium by quantitative analysis of anti-rocuronium IgG.

    Cross-reactivity against rocuronium by quantitative analysis of anti-rocuronium IgG.

    Measured: 18 months

  24. Evaluate the persistence of antibodies (IgE and IgG4 against quaternary ammoniums and suxamethonium) detected at 10 weeks since the last exposure to ECT.

    Persistence of antibodies detected at 10 weeks

    Measured: 10 weeks

  25. Evaluate the persistence of antibodies (IgE and IgG4 against quaternary ammoniums and suxamethonium) detected at 6 months since the last exposure to ECT.

    Persistence of antibodies detected at 6 months

    Measured: 6 months

  26. 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.

    Antibody profile before exposure to NMBA and the potential link with previous drug exposures in the previous year

    Measured: 18 months

  27. Evaluate the influence of hormonal changes induced by ECT on immunization.

    Influence of hormonal changes on immunization

    Measured: 18 months

  28. Incidence of specific IgE antibodies against quaternary ammonium, suxamethonium and rocuronium at 2 weeks.

    Incidence of specific IgE antibodies against quaternary ammonium suxamethonium and rocuronium (via ImmunoCAP and ELISA).

    Measured: 2 weeks

  29. Incidence of specific IgE antibodies against quaternary ammonium, suxamethonium and rocuronium at 4 weeks.

    Incidence of specific IgE antibodies against quaternary ammonium suxamethonium and rocuronium (via ImmunoCAP and ELISA).

    Measured: 4 weeks

  30. Incidence of specific IgE antibodies against quaternary ammonium, suxamethonium and rocuronium at 10 weeks.

    Incidence of specific IgE antibodies against quaternary ammonium suxamethonium and rocuronium (via ImmunoCAP and ELISA).

    Measured: 10 weeks

  31. Incidence of specific IgE antibodies against quaternary ammonium, suxamethonium and rocuronium at 6 months.

    Incidence of specific IgE antibodies against quaternary ammonium suxamethonium and rocuronium (via ImmunoCAP and ELISA).

    Measured: 6 months

  32. Incidence of specific IgG against quaternary ammonium, suxamethonium and rocuronium at 2 weeks.

    Incidence of specific IgG antibodies against quaternary ammonium suxamethonium and rocuronium (via ImmunoCAP and ELISA).

    Measured: 2 weeks

  33. Incidence of specific IgG against quaternary ammonium, suxamethonium and rocuronium at 4 weeks.

    Incidence of specific IgG antibodies against quaternary ammonium suxamethonium and rocuronium (via ImmunoCAP and ELISA).

    Measured: 4 weeks

  34. Incidence of specific IgG against quaternary ammonium, suxamethonium and rocuronium at 10 weeks.

    Incidence of specific IgG antibodies against quaternary ammonium suxamethonium and rocuronium (via ImmunoCAP and ELISA).

    Measured: 10 weeks

  35. Incidence of specific IgG against quaternary ammonium, suxamethonium and rocuronium 6 months.

    Incidence of specific IgG antibodies against quaternary ammonium suxamethonium and rocuronium (via ImmunoCAP and ELISA).

    Measured: 6 months

  36. Incidence of specific IgG4 against quaternary ammonium, suxamethonium and rocuronium at 2 weeks.

    Incidence of specific IgG4 antibodies against quaternary ammonium suxamethonium and rocuronium (via ImmunoCAP and ELISA).

    Measured: 2 weeks

  37. Incidence of specific IgG4 against quaternary ammonium, suxamethonium and rocuronium at 4 weeks.

    Incidence of specific IgG4 antibodies against quaternary ammonium suxamethonium and rocuronium (via ImmunoCAP and ELISA).

    Measured: 4 weeks

  38. Incidence of specific IgG4 against quaternary ammonium, suxamethonium and rocuronium at 10 weeks.

    Incidence of specific IgG4 antibodies against quaternary ammonium suxamethonium and rocuronium (via ImmunoCAP and ELISA).

    Measured: 10 weeks

  39. Incidence of specific IgG4 against quaternary ammonium, suxamethonium and rocuronium at 6 months.

    Incidence of specific IgG4 antibodies against quaternary ammonium suxamethonium and rocuronium (via ImmunoCAP and ELISA).

    Measured: 6 months

  40. Levels of specific IgE antibodies against quaternary ammonium, suxamethonium and rocuronium before the ECT session.

    Levels of specific IgE antibodies

    Measured: 18 months

  41. Levels of specific IgG antibodies against quaternary ammonium, suxamethonium and rocuronium before the ECT session.

    Levels of specific IgG antibodies

    Measured: 18 months

  42. Levels of specific IgG4 antibodies against quaternary ammonium, suxamethonium and rocuronium before the ECT session.

    Levels of specific IgG4 antibodies

    Measured: 18 months

  43. Cytokine profile, particularly pro-tolerogenic, and development of Tregs lymphocytes.

    Profile of cyrokine

    Measured: 18 months

  44. Risk factors: number of ECT sessions, exposure to pholcodine before or during the study, occupational exposure to quaternary ammoniums (hairdressers, cleaning agents, beauticians).

    Risk factors

    Measured: 18 months

  45. Exposures of the previous year to antidepressant, mood stabilizers and anxiolytics.

    Previous exposure to antidepressant, mood stabilizers and anxiolytics

    Measured: 18 months

  46. Assay of ACTH, cortisol at week 0.

    Assay of hormones

    Measured: Week 0

  47. Assay of ACTH, cortisol at week 10.

    Assay of hormones

    Measured: Week 10

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2022
  2. Study start27 Jan 2022
  3. Primary completionSep 2023 (estimated)
  4. Study completionSep 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case only
Time perspective
Prospective
Enrolment
70 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05210062
Sponsor's protocol ID
APHP210659
Acronym
SismoSens
Status last verified
Jan 2022
First submitted
14 Jan 2022
Last updated
12 Apr 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

An observational study of Depression and Mania, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 12 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Aurélie Gouel (01 40 25 70 67, aurelie.gouel@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Evaluate the development of specific antibodies against suxamethonium (type IgG4 anti-suxamethonium) after iterative exposure to ECT at 10 weeks. (time frame: 10 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2022.

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