Evaluation of the Efficacy of Transcranial Magnetic Stimulation on Resistant Auditory Hallucinations in Schizophrenia (HRRENAT)

Treatment of Resistant Auditory Hallucinations in Schizophrenia by Repetitive Transcranial Magnetic Stimulation. Naturalistic Study

This open naturalistic study aims to evaluate the efficacy of rTMS in routine practice on auditory resistant hallucinations (AHR) of patients with schizophrenia. To this end, two stimulation methods will be offered to patients: the rTMS stimulation method and the cTBS stimulation method.We principally use the AHRS scale to evaluate the effectiveness of rTMS on RAH in patients with schizophrenia. Our main hypothesis is that rTMS used under naturalistic conditions, in addition to antipsychotics, would allow a relative improvement of resistant auditory hallucinations assessed by the AHRS scale between baseline and end of treatment in patients with schizophrenia.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia; Transcranial Magnetic Stimulation; Hallucinations, Verbal Auditory
• Intervention / Treatment: Other: The rTMS method; Other: The cTBS method

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Youcef Bencherif; Phone Number: +33 1 43 09 32 32; Email: urcve1@gmail.com
• Study Contact Backup: Name: Rusheentira Thavaseelan; Phone Number: +33 1 43 09 32 32; Email: urcve1@gmail.com

Study Locations

• France
  • Neuilly-sur-Marne, France, 93330
    • Recruiting
    • Etablissement public de santé de Ville-Evrard
    • Contact: Youcef Bencherif; Phone Number: +33 1 43 09 32 32; Email: urcve1@gmail.com
    • Contact: Rusheentira Thavaseelan; Phone Number: +33 1 43 09 32 32; Email: urcve1@gmail.com
    • Sub-Investigator: Noomane BOUAZIZ, Dr.
    • Principal Investigator: Dominique JANUEL, Pr.
    • Sub-Investigator: René BENADHIRA, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient over 18 years of age
• Patient diagnosed with schizophrenia according to DSM-V criteria (Diagnostic and Statistical Manual of Mental Disorder V5, 2013)
• Presence of auditory hallucinations: Resistant auditory hallucinations: resistance to treatment with 2 different well-conducted antipsychotics.
• Patient agreeing to participate in the study and having signed an informed consent
• Patient with French language skills
• Affiliation to a social security system
• Women of childbearing age must be on contraception and have a negative pregnancy test (βHCG)

Exclusion Criteria:

• Have a contraindication to MST: intracranial foreign body, unstabilized epilepsy, cochlear implant
• Presence of an unstabilized medical condition
• Pregnant woman (Women of childbearing age without effective contraception)
• Current or less than one month old engagement in another research protocol
• A person who is subject to a safeguard of justice measure
• An adult under curatorship
• Minor patients with mental health problems
• Pregnant or breastfeeding women
• A person in a social fragility (Persons deprived of liberty by a judicial or administrative decision, hospitalized persons)
• Persons incapable or unable to give consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: The rTMS method; The treatment lasts 2 weeks with 20 rTMS sessions at a rate of 2 sessions per day. Each session lasts 20 minutes with a one hour break between sessions. The application of rTMS will be done on the left temporo-parietal junction.	Other: The rTMS method; The patient receives treatment under naturalistic conditions in routine practice.
Other: The cTBS method; The treatment lasts 15 days with 45 sessions of cTBS at a rate of 3 sessions per day. The session lasts 40 seconds and consists of 3 pulses at 50Hz repeated every 200 milliseconds (5Hz) to reach a total of 600 pulses, with a 15 minute break between sessions. The application of cTBS will be performed on the left temporo-parietal junction.	Other: The cTBS method; The patient receives the treatment under naturalistic conditions in routine practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The evolution will be evaluated mainly with the AHRS (Auditory Hallucinations Rating Scale)	Refer to the definition of AHRS above (in Primary Outcome Measure)	Baseline and at the end of the treatment, also at 1 month and 3 months after the end of the treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate: a response is defined as a decrease greater than or equal to 30% of total AHRS score from baseline to end of treatment.	Refer to the definition of AHRS above	Baseline and at the end of the treatment
Rate of patients with an end-of-treatment score < 3 on the Positive And Negative Syndrome Scale (PANSS) "Hallucinatory Behavior" item	The PANSS is a 30 items scale rated from 1 (absent) to 7 (extreme), that assesses psychopathological symptoms observed in patients with psychotic states, particularly schizophrenia.	Baseline and at the end of the treatment
Cognitive symptoms: Montreal Cognitive Assessment (MOCA), Stroop	The MoCA scale is the most sensitive rapid assessment test and provides the broadest evaluation of cognitive functions (attention, concentration, executive functions, memory, language, visualconstructive abilities, abstraction, calculation, orientation). It tends to replace the MMSE in clinical practice. A score < 26 (25 if cultural level < 3 = primary diploma = CEP) is considered abnormal. The Stroop scale evaluates the capacity for attention and inhibition; thus, it allows to measure the level of interference generated by the automatisms in the accomplishment of a task. The result of the test allows us to see if the person is correctly inhibiting the response (values greater than 0, positive) or if there are significant interference problems (if it is a negative value).	Baseline and 1 month after the end of treatment
Addictive attitudes: number of cigarettes/d (tobacco), The Cannabis Abuse Screening Test (CAST), Marijuana Craving Questionnaire (MCQ)	The CAST is a 6-item scale for identifying problematic cannabis use. Each of these items describes use behaviors or problems encountered with cannabis use. The CAST score determines the patient's level of dependence. A score of 1 or less means low risk. A score of 2 means moderate risk. A score of 3 or higher means high risk. The MCQ self-report scale is a questionnaire on marijuana craving. It consists of four constructs or factors that characterize cannabis craving: compulsivity, emotionality, expectancy and determination. A separate score is calculated for each factor. The MCQ can be used to measure cue-induced craving in a research setting or natural craving in cannabis-dependent individuals presenting for treatment.	Baseline and at the end of the treatment
Mood: Calgary Depression Scale for Schizophrenia (CDSS)	The CDSS, is designed to assess depression in people with schizophrenia. It takes into account negative symptomatology and possible extrapyramidal effects of neuroleptics. The questionnaire consists of 9 items covering the last 2 weeks. Each item is evaluated on a 4 points Likert scale ranging from : "Absent" (0) to "Severe" (3). The total score is obtained by adding the items and gives a score out of 27.	Baseline and the end of the treatment
Quality of life: The Subjective Quality of Life Scale (S-QoL)	The SQoL questionnaire is a self-administered quality of life scale that assesses quality of life in people with schizophrenia from the patient's perspective. The questionnaire has 18 items, each item is rated on a 4 points Likert scale ranging from: "Much less" to "More than desired". Scores range from 0 to 100; higher scores represent better quality of life.	Baseline and end of treatment, also at 1 month and 3 months after the end of the treatment
Clinical Global Impressions (CGI) Scale	Clinical Global Impression (CGI) scales are measures of symptom severity, response to treatment, and treatment effectiveness in treatment studies of patients with mental disorders.	Baseline and end of treatment, also at 1 month and 3 months after the end of the treatment

Collaborators and Investigators

• Sponsor: Dominique JANUEL
• Investigators: Study Director: Dominique JANUEL, Clinical research unit, EPS Ville Evrard; Principal Investigator: Noomane BOUAZIZ, Clinical research unit, EPS Ville Evrard

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2022
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: July 24, 2024
• First Submitted That Met QC Criteria: September 12, 2024
• First Posted (Estimated): September 19, 2024

Study Record Updates

• Last Update Posted (Estimated): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 12, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: schizophrenia; Transcranial magnetic stimulation; TMS; TBS; hallucinations; Theta burst stimulation; resistant auditory hallucinations; a improvement; real-life conditions
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Schizophrenia Spectrum and Other Psychotic Disorders; Perceptual Disorders; Schizophrenia; Hallucinations
• Other Study ID Numbers: 2021-A02698-33

Drug and device information, study documents

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