Voice-Based Biomarkers: a Novel Approach to Monitoring and Predicting Schizophrenia Relapses

NCT ID: NCT06613334

Last Updated: 2024-11-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-04
• Study Completion Date: 2026-10-04

Brief Summary

Schizophrenia is a serious psychiatric illness affecting approximately 25 million people worldwide. Patients with schizophrenia experience hallucinations, auditory illusions, disordered thinking, movement disorders, cognitive impairment and social isolation. Treatments with antipsychotics have proven effective in improving their living conditions, but poor compliance results in relapses and rehospitalizations for the majority of patients, which often results in a worsening of residual symptoms. The prevention of these relapses is a major issue in the care of these patients and frequent monitoring is necessary. The use of a simple, rapid and inexpensive tool to monitor symptoms and treatment effect in schizophrenia could improve the effectiveness of the treatment of these patients and prevent relapses. Speech is a good candidate as a biomarker in the monitoring of patients with schizophrenia. Schizophrenia is accompanied by speech disorders including poor speech, variations in tone or intensity or even difficulties in organizing speech.

Detailed Description

Schizophrenia is a highly complex disease of unknown origin. It is characterized by a heterogeneous etiology and variable clinical manifestations. Numerous studies have investigated genetic, biochemical or neurodevelopmental factors of the pathology, without providing a definitive answer. The environmental factor is also analyzed, especially urban density and pollution. Finally, the immune pathway, in particular neuroinflammation, has been studied. Certain parasites, such as Toxoplasma, may be involved in the development of schizophrenia in combination with genetic factors. All these studies tend to show that the parasite/gene/environment association would influence the development of schizophrenia, but the origins remain unclear and a more complete knowledge of the pathophysiology is needed to improve diagnosis and patient management through new therapeutic targets.

More than 80% of patients with schizophrenia have language abnormalities. These abnormalities are manifested in syntax, semantics and phonology. The most common include monotonous intonation, poverty of speech, increased pauses, lack of spontaneity, and disruption of speech coherence. As speech is an important factor in social interaction, patients have great difficulty in maintaining their social relationships.

A major problem in schizophrenia is the discontinuation or misuse of antipsychotic treatment, which leads to relapse and additional hospital costs. According to a 2013 study, 50% of patients discontinue treatment after six months, often leading to decompensations.To avoid relapses, clinicans can either administer hetero-questionnaire to monitor the patients' symptoms or monitor treatment adherence.

To monitor symptoms, clinicians have at their disposal various standardized questionnaires such as the PAANS. However, those tests are time-intensive.

To monitor treatment adherence, clinicians can use blood drug concentrations as an evidence of compliance, although this method is invasive, and requires costly administration coordination between healthcare profesionnals and patients. There are also several standardized tests to monitor adherence, such as the clinician-administered BARS questionnaire and the self-administered BEMIB. These measures have often been criticized due to factors such as recall bias and poor self-perception, which limit the accuracy of patient reports and overestimate adherence.

It is therefore essential to develop new tools to objectively measure evolution of symptoms and treatment effects to detect onset of relapses, without increasing the burden on patients' daily lives.

Speech voice markers stand out because they have characteristics that make it easy to use in clinical practice and can be easily integrated into patients' daily lives. Advances in signal processing and machine learning algorithms now make it possible to measure the different components of speech: phonatory skills, articulation, the different linguistic levels (semantics, syntax, morphology, pragmatics) as well as the specific disfluencies of spontaneous speech.

These different speech markers have been validated in different neurological and psychiatric pathologies: in particular, Parkinson's disease, Huntington's disease, depression, suicidal risk, and schizophrenia. These markers of speech in psychiatry are now generalizing across languages and are also being taken into patients' homes to measure changes in patient states.

Distinctive voice characteristics have been a feature of schizophrenia since it was first defined. They are often associated with negative symptoms, such as the inability to show emotion, and with observed social impairments. It has been quantitatively observed that people with schizophrenia have poorer speech, more pauses, distinctive tones, and differences in voice intensity.

Studies have shown antipsychotics also affect language, since patients are dopamine-deficient, and blockade of these receptors by antipsychotics would exacerbate language impairments. In addition, blockade of the striatal dopamine receptor leads to extrapyramidal side effects, causing tremors, muscle rigidity, and tics that interfere with the joint movements required for speech.

Therefore, voice and language are very good candidates as biomarkers in monitoring both symptoms and treatment effects in schizophrenia to detect onsets of relapses.

The aim of this study is to determine whether voice biomarkers can be used to objectively monitor symptoms and treatment effects in schizophrenia in order to detect onset of relapses.

Conditions

Schizophrenia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Schizophrenic patients treated with a primary treatment

Study's interventions:

• 4 blood tests (inclusion visit, at follow-up visits at 2 and 4 months after inclusion, at the end-of-study visit at 6 months after inclusion) to measure the blood concentration of antipsychotic treatment (risperidone or paliperidone)
• completion of self-questionnaires and voice interviews of the application developed by CALLYOPE

Group Type: EXPERIMENTAL

Blood test: measurement of plasma antipsychotic concentration

Intervention Type: BIOLOGICAL

Four blood tests are prospectively realized per patient during the study to measure the plasma concentration of antipsychotics (primary treatment: risperidone/paliperidone, olanzapine or aripiprazole). These blood samples are taken at the inclusion visit, at the follow-up visits 2 and 4 months after the inclusion visit, then at the end-of-study visit 6 months after the inclusion visit.

Voice interviews and questionnaires carried out via the CALLYOPE application

Intervention Type: OTHER

Voice interviews carried out via the Callyope application: they consist of a series of tests, divided into two parts: Structured tasks (same content for each participant) and Semi-structured tasks (content varies for each participant).

The simultaneous analysis of several speech tasks allows us to break down the different stages of speech production and the important factors that influence its achievement.

In addition, patients will complete self-questionnaires via the application. Finally, lifestyle habits (sleep duration and number of steps) will be recorded via the application.

These different tests will be carried out on the application at the inclusion visit (M0), then every month (M1, M2, M3, M4, M5) until the end of study visit (M6).

Interventions

Blood test: measurement of plasma antipsychotic concentration

Four blood tests are prospectively realized per patient during the study to measure the plasma concentration of antipsychotics (primary treatment: risperidone/paliperidone, olanzapine or aripiprazole). These blood samples are taken at the inclusion visit, at the follow-up visits 2 and 4 months after the inclusion visit, then at the end-of-study visit 6 months after the inclusion visit.

Intervention Type: BIOLOGICAL

Voice interviews and questionnaires carried out via the CALLYOPE application

Voice interviews carried out via the Callyope application: they consist of a series of tests, divided into two parts: Structured tasks (same content for each participant) and Semi-structured tasks (content varies for each participant).

The simultaneous analysis of several speech tasks allows us to break down the different stages of speech production and the important factors that influence its achievement.

In addition, patients will complete self-questionnaires via the application. Finally, lifestyle habits (sleep duration and number of steps) will be recorded via the application.

These different tests will be carried out on the application at the inclusion visit (M0), then every month (M1, M2, M3, M4, M5) until the end of study visit (M6).

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Affiliated to a social security or other social protection scheme
• Diagnosed with schizophrenia according to the DSM-5 (code F20)
• Stable state without duration criteria
• Main treatment with risperidone or paliperidone, aripiprazole, olanzapine in oral or long-acting injectable form
• Complementary treatment with an antipsychotic for anxiolytic or sedative purposes: chlorpromazine, loxapine or cyamemazine
• Able to speak and read French
• Able to perform speech evaluations
• Able to answer questionnaires on smartphone
• May be under curatorship or guardianship
• Agreeing to participate in the study and with informed consent signed by the subject, as well as by the legal representative in the case of a person under curatorship or guardianship

Exclusion Criteria

• Suffering from a pathology that impairs French
• Suffering from a neurological pathology: multiple sclerosis, Parkinson's disease, Huntington's disease or neurodegenerative disease
• Treatment with lithium salts
• Anti-epileptic treatment
• Participant in another study involving medication

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier St Anne

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pierre De Maricourt, Dr

Role: PRINCIPAL_INVESTIGATOR

GHU Paris Psychiatry & Neurosciences

Locations

Groupe Hospitalo-Universitaire Paris Psychiatrie et Neurosciences, Paris

Paris, Paris, France

Site Status: RECRUITING

Groupe Hospitalo-Universitaire Paris Psychiatrie & Neurosciences

Paris, , France

Site Status: NOT_YET_RECRUITING

Countries

France

Central Contacts

Pierre De Maricourt, Dr

Role: CONTACT

P.DEMARICOURT@ghu-paris.fr

(0)1 45 65 86 91 ext. +(33)

Philippe Domenech, Pr

Role: CONTACT

philippe.domenech@ghu-paris.fr

(0)1 49 81 22 01 ext. +(33)

Facility Contacts

Pierre De Maricourt, Dr

Role: primary

P.DEMARICOURT@ghu-paris.fr

+33145658941

Pierre De Maricourt, Dr

Role: primary

P.DEMARICOURT@ghu-paris.fr

01 45 65 86 91 ext. +33

Other Identifiers

D23-P038

Identifier Type: -

Identifier Source: org_study_id