ECT in Ultra-resistant Schizophrenia (SURECT)

Clinical Trial Comparing Two Electroconvulsive Therapy (ECT) Application Schemas in Ultra-resistant Schizophrenia

The effects of the ECT in schizophrenia ultra-resistant were studied in short times (4-6 months in most studies with follow-up). The literature identified a high relapse rate of 32% in the weeks to months after ECT discontinuation. The use of the ECT in the prevention of the relapse is partially known. In an empirical way, experts recommend protocols of prevention of the relapse going from 6 to 12 months. Nevertheless, the profit of a long cure (12 months) compared with a short cure (6 months) was never determined. Therefore, the investigators decided to lead a prospective randomized controlled study in order to compare the response rates between the two strategies of clozapine and ECT combinations applied to URS patients. The treatment consisted either in a short therapy of six months or a longer course of therapy of twelve months. To the investigators' knowledge, it is the first study which compares two ECT strategies (both the short duration and the longer one) for the treatment of URS patients.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia; Electroconvulsive Therapy
• Intervention / Treatment: Device: Electroconvulsive therapy

• Study Type: Interventional
• Enrollment (Anticipated): 64
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Maud Rothärmel, MD; Phone Number: 0033232956825; Email: maud.rotharmel@ch-lerouvray.fr
• Study Contact Backup: Name: Aline Augustynen; Phone Number: 0033232956825; Email: aline.augustynen@ch-lerouvray.fr

Study Locations

• France
  • Bordeaux, France, 33076
    • Not yet recruiting
    • Centre Hospitalier Charles Perrens
    • Contact: Clelia Quiles, Md,PhD
    • Principal Investigator: Clelia Quiles, MD,PhD
  • Cadillac, France, 33410
    • Not yet recruiting
    • Centre Hospitalier de Cadillac
    • Contact: Patrick Le Bihan, MD
    • Principal Investigator: Patrick Le Bihan, MD
  • Caen, France, 14033
    • Recruiting
    • CHU de Caen
    • Contact: Pierrick LEBAIN, MD
    • Principal Investigator: Pierrick Lebain, MD
    • Sub-Investigator: Clément Nathou, MD, PhD
    • Sub-Investigator: Sonia Dollfus, MD,PhD
  • Clermont-Ferrand, France
    • Recruiting
    • Clermont-Ferrand Hospital
    • Contact: Pierre-Michel Llorca, MD, PhD
  • Montpellier, France
    • Recruiting
    • Montpellier University Hospital
    • Contact: Jerôme Attal, MD
  • Nantes, France, 44000
    • Recruiting
    • CHU de Nantes
    • Contact: Anne Sauvaget, MD,PhD
    • Principal Investigator: Anne Sauvaget, MD,PhD
    • Sub-Investigator: Samuel Bulteau, MD,PhD
    • Sub-Investigator: Jean-Marie Vanelle, MD,PhD
    • Sub-Investigator: Edouard Laforgue, MD
  • Neuilly-sur-Marne, France
    • Not yet recruiting
    • EPS Ville Evrard
    • Contact: Dominique Januel, MD, PhD
    • Principal Investigator: Noomane Bouaziz, MD
    • Principal Investigator: Dominique Januel, MD, PhD
  • Paris, France, 75014
    • Recruiting
    • Centre Hospitalier Saint Anne
    • Contact: Marie-Odile Krebs, MD,PhD
    • Principal Investigator: Marie-Odile Krebs, MD,PhD
    • Principal Investigator: Marion Plaze, MD
  • Poitiers, France, 86021
    • Recruiting
    • Centre Hospitalier Henri Laborit
    • Contact: Nemat Jaafari, MD,PhD
    • Principal Investigator: Nemat Jaafari, Md,PhD
  • Toulouse, France, 31059
    • Recruiting
    • CHU de Toulouse
    • Contact: Christophe Arbus, MD
    • Principal Investigator: Christophe Arbus, MD
    • Sub-Investigator: Marie Sporer, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with URS: patients who continue to experience persistent positive psychotic symptoms: item score of 4 (moderate) on at least two of four positive symptoms on the BPRS (grandiosity, suspiciousness, hallucinations and unusual thoughts), current presence of at least moderately severe illness on the total BPRS-18 (45) and a score of 4 (moderate) on the CGI-S, despite a period of clozapine therapy of at least 6 weeks with a plasma concentration of 350 ng/ml and at least two unsuccessful previous treatment trials with conventional or atypical antipsychotic drugs from two distinct families at a dose 600 mg of chlorpromazine equivalents.
• Age: from 18 to 55
• Patients with stable treatments for at least 8 weeks (antipsychotics, mood stabilizers and antidepressants).
• Participants who gave their informed, written consents and agreement of their guardian for the patients under guardianship
• Patients deprived of liberty if they gave their informed, written consents

Exclusion Criteria:

• Current affective episode according to DSM-5 criteria;
• ECT within (the last) 6 months;
• Unstable epilepsy ; severe neurological or systemic disorder that could significantly affect cognition, behavior, or mental status (other than late dyskinesia or neuroleptic-induced parkinsonism);
• Severe substance use disorders (other than nicotine or caffeine) according to DSM-5 criteria.
• Concomitant use of antiepileptics and benzodiazepines apart from lamotrigine
• Women of childbearing age with no adequate contraception, pregnant or lactating women;
• Patients having contraindications to etomidate or any of its excipients;
• Patients having contraindications to neuromuscular blocking agents;
• Patients participating or having participated in an interventional clinical trial within 30 days prior to the inclusion visit;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Short ECT arm; In the short arm, bitemporal ECT is administered twice a week during the first 6 weeks. Afterwards, it is administered once a week during 4 weeks. After that, the patients will have one ECT every 3 weeks during 6 weeks. Lastly, patients will receive one ECT each month during 2 months.	Device: Electroconvulsive therapy; Electroconvulsive therapy is administered through electrodes positioned bilaterally (for quicker efficacy) on the frontotemporal region. The stimulation dose is determined by titration method, during the first ECT session. The dose for therapeutic stimulation will be twice the seizure threshold. This dose may be increased as the crisis does not meet the effectiveness criteria, as is recommended. For patients undergoing ECT, an intravenous injection of etomidate (between 0.1 and 0.7 mg/kg) and suxamethonium chloride (0.8 and 1.2 mg/kg) is performed. The required doses are adapted according to each patient by the anaesthetist and they are documented in the patients' files. A mixture of etomidate and propofol can be used in second-line or just propofol in third-line (no more than 2mg/kg).
Active Comparator: Long ECT arm; In the long arm, bitemporal ECT is administered twice a week during the first 12 weeks. Afterwards, it is administered once a week during 8 weeks. After that, the patients will have one ECT every 3 weeks during 12 weeks. Lastly, patients will receive one ECT each month during 4 months.	Device: Electroconvulsive therapy; Electroconvulsive therapy is administered through electrodes positioned bilaterally (for quicker efficacy) on the frontotemporal region. The stimulation dose is determined by titration method, during the first ECT session. The dose for therapeutic stimulation will be twice the seizure threshold. This dose may be increased as the crisis does not meet the effectiveness criteria, as is recommended. For patients undergoing ECT, an intravenous injection of etomidate (between 0.1 and 0.7 mg/kg) and suxamethonium chloride (0.8 and 1.2 mg/kg) is performed. The required doses are adapted according to each patient by the anaesthetist and they are documented in the patients' files. A mixture of etomidate and propofol can be used in second-line or just propofol in third-line (no more than 2mg/kg).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The response rate (a 30% decrease in the Positive and Negative Syndrome Scale (PANSS)) at 15th month	The response rate (a 30% decrease in the PANSS, ranging from 30, the minimum, to 210, the most severe score) at 15th month	three months after the end of the treatment (i.e. 9 and 15 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The response rate (a 30% decrease in the Brief Psychiatric Rating Scale (BPRS))	The response rate (a 30% decrease in the BPRS, ranging from 18, the minimum, to 126, the most severe score) at 15th month.	three months after the end of the treatment (i.e. 9 and 15 months)
The response rate (a 30% decrease in the BPRS) at different times of the study	The response rate (a 30 % decrease in the BPRS) at 2, 4, 6 and 12 months.	2, 4, 6 and 12 months
Response rate (a 30% decrease in the PANSS) at different times of the study	The response rate (a 30 % decrease in the PANSS) at 2, 4, 6 and 12 months.	2, 4, 6 and 12 months
Neuropsychological assessment- MMSE	The scores and variations of the Mini Mental Status Examination (MMSE) at -1, 6 and 15 months.	-1, 6 and 15 months
Neuropsychological assessment- SSTICS	The scores and variations of the Subjective Scale To Investigate Cognition In Schizophrenia (SSTICS, scores ranging from 0 to 84, the most severe score) at -1, 6 and 15 months.	-1, 6 and 15 months
Neuropsychological assessment- Grober and Buschke test	The scores and variations of the test of Grober and Buschke at -1, 6 and 15 months.	-1, 6 and 15 months
Neuropsychological assessment- test of doors	The scores and variations of the test of doors at -1, 6 and 15 months.	-1, 6 and 15 months
Neuropsychological assessment- test of d2	The scores and variations of the test of d2 at -1, 6 and 15 months.	-1, 6 and 15 months
Neuropsychological assessment - "figure de Rey" test	the scores ans variations of the test of " figure de Rey" at -1, 6 and 15 months.	-1, 6 and 15 months
Other clinical assessment- HAMD-21	The scores and variations of the Hamilton Rating Scale-21 items (HAMD-21, scores ranging from 0 to 64, the most severe score) at day 1 and 2, 4, 6, 9, 12 and 15 months.	day 1 and 2, 4, 6, 9, 12 and 15 months
Other clinical assessment-YMRS	The scores and variations of the Young Mania Rating Scale (YMRS, scores ranging from 0 to 60, the most severe score) at day 1 and 2, 4, 6, 9, 12 and 15 months.	day 1 and 2, 4, 6, 9, 12 and 15 months
Other clinical assessment-GAF	The scores and variations of the Global Assessment Functioning (GAF, scores ranging from 0 to 100, the best score) at day 1 and 2, 4, 6, 9, 12 and 15 months.	day 1 and 2, 4, 6, 9, 12 and 15 months
Other clinical assessment-MOAS	The scores and variations of the Modified Overt Aggression Scale (MOAS, scores ranging from 0 to 100, the most severe score) at day 1 and 2, 4, 6, 9, 12 and 15 months.	day 1 and 2, 4, 6, 9, 12 and 15 months

Collaborators and Investigators

• Sponsor: Centre Hospitalier du Rouvray
• Collaborators: University Hospital, Rouen; University Hospital, Montpellier; University Hospital, Bordeaux; University Hospital, Clermont-Ferrand; University Hospital, Caen; University Hospital, Toulouse; Nantes University Hospital; Centre Hospitalier St Anne; Centre Hospitalier Henri Laborit; Centre hospitalier de Ville-Evrard, France; Hôpital Louis Mourier; Centre Hospitalier de Cadillac

Publications and helpful links

General Publications

• Moulier V, Krir MW, Dalmont M; SURECT Group; Guillin O, Rotharmel M. A prospective multicenter assessor-blinded randomized controlled study to compare the efficacy of short versus long protocols of electroconvulsive therapy as an augmentation strategy to clozapine in patients with ultra-resistant schizophrenia (SURECT study). Trials. 2021 Apr 15;22(1):284. doi: 10.1186/s13063-021-05227-3.

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2018
• Primary Completion (Anticipated): October 4, 2023
• Study Completion (Anticipated): October 4, 2023

Study Registration Dates

• First Submitted: April 11, 2018
• First Submitted That Met QC Criteria: May 18, 2018
• First Posted (Actual): May 31, 2018

Study Record Updates

• Last Update Posted (Actual): September 16, 2020
• Last Update Submitted That Met QC Criteria: September 15, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: 2017-A02657-46

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No