First-episode PsychosisPEPAMARKERNCT05384392
Biomarkers Predictive of Thymic Evolution and Therapeutic Response at 2 Years in Patients With a First Psychotic Episode
A study testing Recorded interview, Clinical scales and Blood sample in people with First-episode Psychosis, run by University Hospital, Brest at 5 sites in France.
Trial summary
Psychosis is a severe, common, and disabling psychological disorder. An epidemiological study conducted in England reported an incidence of 34 new cases per 100,000 person-years, with a peak between 16 and 19 years of age. Read more about this study
- Who is it for?
- Ages 15 to 30 years
- Conditions the study is for
- First-episode Psychosis
- What is being tested?
- Recorded interview, Clinical scales and Blood sample
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 217 participants
- Where
- 5 sitesFrance
- Study dates
- 27 Mar 2025to Mar 2030
- Phase
- Interventional
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 15 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patient with a first episode of psychosis,
- Aged between 15 and 30 years,
- Able to consent and having signed a consent form (parental consent for minors).
Who cannot join
- Introduction or increase of antipsychotic and/or antidepressant and/or thymoregulatory treatment in the last month,
- Mother tongue other than French,
- Psychotic episode due to an organic disorder,
- Psychotic episode induced by the use or withdrawal of toxic substances with severe dependence ,
- Intellectual deficit,
- Chronic inflammatory disease,
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- Immunomodulatory treatment,
- Contraindication to MRI,
- Pregnant or breastfeeding woman,
- Patient under court protection, guardianship, curatorship or deprived of liberty.
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
France5 sites, 5 recruiting
- Recruiting
Dr Efflam BREGEON
Angers, 49033
Efflam BREGEON, Dr, 02 41 80 75 88, efflam.bregeon@ch-cesame-angers.fr
Bénédicte GOHIER, Dr
- Recruiting
Dr Florian STEPHAN
Brest, 29609
Florian STEPHAN, florian.stephan@chu-brest.fr
Christophe LEMEY, christophe.lemey@chu-brest.fr
- Not yet recruiting
Dr Anne SAUVAGET
Nantes, 44093
Anne SAUVAGET, Dr, anne.sauvaget@chu-nantes.fr
Anne SAUVAGET
- Recruiting
Dr Dominique DRAPIER
Rennes, 35703
DRAPIER Dominique, Dr, d.drapier@ch-guillaumeregnier.fr
Dominique DRAPIER, Dr
- Recruiting
Dr Vincent CAMUS
Tours, 37044
CAMUS Vincent, Pr, vincent.camus@univ-tours.fr
Vincent CAMUS
About this study
Psychosis is a severe, common, and disabling psychological disorder. An epidemiological study conducted in England reported an incidence of 34 new cases per 100,000 person-years, with a peak between 16 and 19 years of age. Following a first psychotic episode, two clinical evolutions are possible: thymic psychosis (17%) and non thymic psychosis (83%). The first includes bipolar disorders with a psychotic component and major depressive disorders with a psychotic component; the second, other psychotic disorders, mainly schizophrenia. One of the major difficulties encountered is the frequent impossibility of specifying the type of psychosis at the beginning of the psychotic episode. However, these disorders require different therapies, particularly medication. This leads to a delay in diagnosis with a high risk of relapse.
The semiological study of these diseases being carried out within the framework of interviews, it seems interesting to be able to record these and to obtain a quantitative and objective measurement through the study of language. The use of machine learning has made it possible to distinguish patients with schizophrenia from those with bipolar disorder by graphical analysis of language in a more efficient way than with clinical scales.Moreover, it is possible to identify linguistic markers: thus, an alteration of syntactic structures and prosody would be more present in non-thymic than in thymic psychoses.
Read more
Paraclinical markers are also emerging. In particular, the link between inflammation and mental disorders.For example, an increase in IL-8 has been found only in thymic psychoses.
In this context, it seems essential to be able to distinguish these disorders as early as possible through the combined use of clinical and paraclinical markers, and to be able to better understand their pathophysiology.
- Conditions
- First-episode Psychosis
- Being tested
- Recorded interview, Clinical scales, Blood sample
- Keywords
- Bipolar Disorder, Schizophrenia
- Medical subject headings
- Bipolar Disorder, Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recorded interviewOther
A recorded clinical interview, transcribed verbatim and blinded analyzed
Clinical scalesOther
Answering to clinical scales : PANSS (Positive and Negative Syndrome Scale); BPRS (Brief Psychiatric Rating Scale); CDSS (Calgary Depression Scale for Schizophrenia); MADRS (Montgomery-Åsberg Depression Rating Scale); Altman; YMRS (Young Mania Rating Scale); GAF (Global Assessment of Functioning); SF-36 (36-Item Short Form Survey); CGI-S (Clinical Global Impression Scale) et CGI-I (CGI-Improvement)
Blood sampleBiological
Blood collection of inflammatory markers (IL-1, sIL-2R, IL-4, IL-6, IL-8 and TNF levels) and 2 EDTA tubes and 2 dry tubes for biological collection (plasma bank and serum bank). This blood sample will be taken during routine sampling.
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | All patients included in the study will be required to complete the examinations specified in the protocol. Receives: Other: Recorded interview; Other: Clinical scales; Biological: Blood sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of thymic evolution
The primary endpoint is the thymic evolution (yes or no) of the initial psychotic episode The prosodic linguistic markers (fundamental frequency and latency) will be measured at Day 0 during a routine clinical interview and wil enable to build a predictive model to predict the thymic evolution at 2 years in patients with a first psychotic episode. This is main objective of study.
The assessment will be measured the answer yes or no, at 2 years, at question, is the psychotic episode a thymic disorder?".
Measured: Day 0, Year 2
Secondary outcomes (12)
Evaluation of thymic evolution according syntactic linguistic markers
The thymic evolution will be evaluated according syntactic linguistic markers at Day 0 during a clinical interview.
Syntactic complexity is assessed using lexical density (%), lexical diversity (%), and the average number of words per clause. The use of the singular first-person pronoun "je" and speech disfluencies are also foregrounded in our project.
Measured: Day 0
Evaluation of thymic evolution according semantic linguistic markers
The thymic evolution will be evaluated according semantic linguistic markers at Day 0 during a clinical interview.
Semantic marker is grounded in a method for measuring semantic coherence called "latent semantic analysis (LSA)". LSA entails computing the cosine similarity between two vectors in each comparison of documents, i.e. between two sentences or between two turn-takings. Semantic coherence is consequently expressed by a value between -1 and 1.
Measured: Day 0
Inflammatory markers
Assessment according inflammatory markers (IL-1, sIL-2R, IL-4, IL-6, IL-8 and TNF levels) at T0 during the initial biological work-up. The unit of measure is pg/mL for the inflammatory markers.
Measured: Day 0
Evaluation of thymic evolution according PANSS
The thymic evolution will be evaluated according Positive and Negative Syndrome Scale (PANSS). The Positive and Negative Syndrome Scale (PANSS) is an established psychiatric rating system that is an operationalized, drug-sensitive instrument that offers balanced representation of positive and negative symptoms and estimates their relationship to one another and to global (or general) psychopathology. The scale has 30 items to explore and is scored from 1 (absence) to 7 (extreme).
Measured: Day 0, Year 1, Year 2
Evaluation of thymic evolution according BPRS
The Brief Psychiatric Rating Scale (BPRS) is a tool clinicians or researchers use to measure psychiatric symptoms such as anxiety, depression, and psychoses.
Persons having or suspected of having schizophrenia or other psychotic disorder manifest the disorder in multiple ways. The BPRS assesses the level of 18 symptom constructs such as hostility, suspiciousness, hallucination, and grandiosity. It is particularly useful in gauging the efficacy of treatment in patients who have moderate to severe psychoses.
It is based on the clinician's interview with the patient. The rater enters a number for each symptom construct that ranges from 1 (not present) to 7 (extremely severe).
Measured: Day 0, Year 1, Year 2
Evaluation of thymic evolution according CDSS
This scale is designed to assess depression in people with schizophrenia. The questionnaire consists of 9 items (depressed mood, hopelessness, self-deprecation, guilt-themed reference thoughts, pathological guilt, morning depression, early arousal, suicidal ideation, and observed depression) covering the last 2 weeks.
4-point Likert-type scale ranging from 0= "absent" to 3= "severe" for each items. More higher score = More severe symptoms.
Measured: Day 0, Year 1, Year 2
Evaluation of thymic evolution according MADRS
The Montgomery-Åsberg Depression Rating Scale (MADRS) is a scale used to assess the severity of depression in patients with mood disorders. It is also frequently used to measure changes brought about by treatment of depression.
It assesses the severity of symptoms in a wide range of areas such as mood, sleep and appetite, physical and psychological fatigue and suicidal ideation.
The scale has 10 items rated from 0 to 6 (> 34 points: the patient is considered to be in severe depression).
Measured: Day 0, Year 1, Year 2
Evaluation of thymic evolution according Altman
The Altman Self-Rating Scale is a short 5-item self-report questionnaire that can be useful in assessing the presence and severity of manic or hypomanic symptoms.
Each of these points has five statements that correspond to scores of 0 to 4; 0 being unchanged from "normal" or baseline, to 4 being clearly manic thoughts or behavior. The subject is asked to choose one statement from each of the five domains that best describes how they have felt over the past week.
Scores above 5 indicate mania or hypomania, with the severity of symptoms increasing with higher scores.
Because this scale is consistent with diagnostic criteria, it can be used effectively as a screening and diagnostic tool despite its brevity.
Measured: Day 0, Year 1, Year 2
Evaluation of thymic evolution according YMRS
The Young Mania Rating Scale (YMRS) is one of the most frequently utilized rating scales to assess manic symptoms. The scale has 11 items and is based on the patient's subjective report of his or her clinical condition over the previous 48 hours.
The YMRS total score ranges from 0 to 60 where higher scores indicate more severe mania.
Measured: Day 0, Year 1, Year 2
Evaluation of thymic evolution according GAF
The Global Assessment of Functioning, or GAF, scale is used to rate how serious a mental illness may be. It measures how much a person's symptoms affect their day-to-day life on a scale of 0 (minimum value) to 100 (maximum value). It's designed to help mental health providers understand how well the person can do everyday activities. The higher subject score, the better subject is able to handle daily activities.
Measured: Day 0, Year 1, Year 2
Evaluation of thymic evolution according SF-36
SF-36 is a set of generic, coherent, and easily administered quality-of-life measures. These measures rely upon patient self-reporting and are now widely utilized for routine monitoring and assessment of care outcomes in adult patients.
The SF-36, as described in the name, is a 36-item patient-reported questionnaire that covers eight health domains: physical functioning (10 items), bodily pain (2 items), role limitations due to physical health problems (4 items), role limitations due to personal or emotional problems (4 items), emotional well-being (5 items), social functioning (2 items), energy/fatigue (4 items), and general health perceptions (5 items). Scores for each domain range from 0 to 100, with a higher score defining a more favorable health state.
Measured: Day 0, Year 1, Year 2
Evaluation of thymic evolution according CGI
Amongst the most widely used of extant brief assessment tools in psychiatry, the CGI is a scale that measures illness severity (CGIS) and global improvement or change (CGIC). The illness severity and improvement sections of the instrument are used frequently in both clinical and research settings. This scale asks that the clinician rate the patient relative to their past experience with other patients with the same diagnosis, with or without collateral information. The CGI has proved to be a robust measure of efficacy in many clinical drug trials, and is asy and quick to administer, provided that the clinician knows the patient well.
The CGI is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill patients). CGI-C scores range from 1 (very much improved) through to 7 (very much worse). Each component of the CGI is rated separately; the instrument does not yield a global score.
Measured: Day 0, Year 1, Year 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2022
- Study start27 Mar 2025
- Primary completionMar 2027 (estimated)
- Study completionMar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for First-episode PsychosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 217 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Brest
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05384392
- Sponsor's protocol ID
- 29BRC21.0196
- Acronym
- PEPAMARKER
- Status last verified
- Jun 2026
- First submitted
- 28 Apr 2022
- Last updated
- 11 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All collected data that underlie results in a publication
Publications
Terrisse R, Lemey C, Kim-Dufor DH, Miglianico L, Stephan F. PEPAMARKER: a multicenter cohort study protocol on predictive biomarkers of affective vs. non-affective trajectories in first-episode psychosis. Front Psychiatry. 2026 Jan 14;16:1702187. doi: 10.3389/fpsyt.2025.1702187. eCollection 2025.
PubMed 41614097