A prospective, randomized, and controlled study comparing two treatment strategies (Dose REduction of Antipsychotics vs. Maintenance treatment) in patients with schizophrenia spectrum disorder after Stratification based on patients’ psychotic PHENotype: a personalized medicine approach

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Les Hopitaux Universitaires De Strasbourg

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Decision date (initial)

2025-05-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

National clinical research hospital program 2021 (PHRC 2021) · Strasbourg University Hospitals

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Dose response

To assess whether an interaction exists between treatment strategy (Dose Reduction (DR) vs. Maintenance Treatment (MT)) and psychotic phenotype (Cycloid Psychosis (CP) vs. non-Cycloid Psychosis), with the hypothesis that the benefit of DR strategy compared to MT in terms of functional remission is larger in the CP than in the non-CP arm (according to both personalized and precision medicine claims).

Secondary objectives 12

1. To confirm a higher rate of functional remission (FR) in the CP-DR than in the CP-MT arm (related to treatment strategy)
2. To confirm a lower rate of FR in the non-CP-DR than in the non-CP-MT arm (related to treatment strategy)
3. To confirm a higher rate of FR in CP than in non-CP (related to characteristics of the phenotype)
4. To evaluate the relapse rate in all arms
5. To evaluate the rate of “successful DR” in CP and non-CP patients as defined by (Tani et al., 2020) o a compliance to the DR schema and to the steps defined in the protocol o AND an absence of a significant relapse (i.e. a new hospitalization, aggressive behavior, suicidal attempt) o AND a reduction of antipsychotic side-effects OR an improvement of subjective well-being, quality of life OR an improvement of social functioning (PSP total score) from baseline
6. To evaluate the therapeutic efficacy index and adherence to treatment in both DR and MT arms
7. To confirm the reduction of side effects with DR relative to MT (cognition, negative symptoms, extrapyramidal side effects, metabolic syndrome, well-being under antipsychotics…)
8. To evaluate the level of social and global functioning (physical activity, leisure,…), and subjective well-being in all arms
9. To evaluate whether the expected arm differences reported above will be (as expected) larger in patients with a history of psychotic episodes vs. patients with a first episode of psychosis (FE-SSD)
10. To identify the individual minimal effective dose (i-MinED) of antipsychotics for CP and non-CP phenotypes in our sample
11. To confirm that the first step of the reduction (i.e. DM), is safe (no significant relapse) and desirable (reduction of side effects, improved functioning) whatever the phenotypes
12. To compare the mean dosage of antipsychotics in all arms and confirm that the dose is lower in the DR than in the MT arms.

Conditions and MedDRA coding

Patient with a diagnosis of schizophrenia spectrum disorder (SSD): schizophrenia, schizophreniform, schizoaffective disorder or brief psychotic episode according to DSM-5

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Patient 18-60 years of age;
2. Patient affiliated to health insurance (beneficiary or beneficiary’s family);
3. Patient informed of the results of the preliminary medical examination;
4. Patient able to understand the aims and risks of the research (assisted by his/her curator, if applicable (if subject under curatorship*))*Subjects under limited guardianship (i.e. French “curatelle”) can participate to the study.
5. Informed consent signed by patient (with assistance of his/her curator, if applicable (if subject under curatorship*))
6. Patient with a diagnosis of schizophrenia spectrum disorder (SSD): schizophrenia, schizophreniform, schizoaffective disorder or brief psychotic episode according to DSM-5;
7. Patient with: a) Either a cycloid psychosis (CP) phenotype according to By-CP (score >=80%; Lozère, 2024) b) Or another (non-CP) psychotic phenotype; (By-CP score < 80%)
8. Outpatient followed by an ambulatory psychiatrist;
9. Patient with an identified caregiver
10. Patient clinically stabilized, for at least 6 months, as defined by a) low intensity of positive symptoms, i.e. PANSS P1, P2 and P3 items < 4.
11. Patient treated with oral antipsychotics (in mono or polytherapy, with second- or first-generation antipsychotics);
12. Patients with a PSP score >70 at baseline

Exclusion criteria 14

1. Patient hospitalized in a psychiatric ward;
2. Patient with a recent psychotic episode (during the last 6 months);
3. Patient treated with long-acting injection of antipsychotics (due to feasibility constraints and to the fact that these treatments remain essentially proposed to non-compliant patients with high risk of acute cessation and loss to follow-up);
4. Patient treated with clozapine (in mono or polytherapy – highly resistant patients, specificities of the relapses under clozapine (Luykx et al., 2020));
5. Patient considered by his psychiatrists to be at serious risk of harm to self or others (e.g. previous aggressive or suicidal behaviors);
6. Neurological or severe medical condition other than psychosis;
7. Pregnancy (verified by urinary test at enrollment for women of childbearing age);
8. Current breastfeeding;
9. Patient involved in another Investigational Medicinal Product trial;
10. Patient in an exclusion period defined by another research protocol;
11. Patient under guardianship (i.e. French ‘tutelle’);
12. Patient with care under constraint
13. Patients deprived of freedom because of a judicial measure.
14. Inability to give the patient the written consent form (emergency situation)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Percentage of patients with functional remission as defined by a PSP (Personal and Social Performance Scale, Nasrallah et al. 2008) score >70 at 24 months follow-up (study endpoint).
2. The PSP will be assessed at different times of the study, both by the treating psychiatrist of the patients (i.e. who is not blind to patients’ treatment arm) and by the Dreams-Phen evaluation team (who will be blind to patients’ treatment arm). The primary endpoint will rely ONLY on the PSP scores at 24 months assessed by the Dreams-Phen evaluation team.
3. This evaluation will be performed during a webmeeting with the patient and his/her caregiver and will be based on the patient’s functioning during the month preceding the evaluation.

Secondary endpoints 11

1. Functional remission as defined by a PSP (Personal and Social Performance Scale, Nasrallah et al., 2008) score >70 at 24 months follow-up (study endpoint) and as assessed by the Dreams-Phen evaluation team.
2. Clinical symptoms will be assessed with the short form of the PANSS (PANSS-6) and will be used by the treating psychiatrists as well as the Dreams-Phen evaluation team at some assessment points for time purposes. Illness severity will be assessed with the Clinical Global Impression (CGI).
3. A relapse will be defined by either as: a) a new hospitalization due to exacerbation of symptoms b) aggressive behavior c) suicidal attempt
4. At the end of the study, a structured interview (inspired by that used in the Radar study; Moncrieff et al. 2019) will be conducted with the patients and his/her caregivers and sent to the treating psychiatrist, in order to confirm the presence or absence of any relapse during the period of the study
5. Therapeutic efficacy index will be assessed with the CGI-difference and adherence to treatment with the MARS (Thompson et al., 2000) from the patient side and the BARS (Byerly et al., 2008) from the psychiatrist side. In addition, drug monitoring will be proposed, in order to check adherence to treatment and to ensure patients’ compliance to the treatment arm.
6. Treatment side-effects will be assessed using the Abnormal Involuntary Movement Scale (AIMS), and Simpson & Angus Scale (SAS), and using the body mass index and biological measures to assess metabolic syndrome. Cognitive functioning will be assessed with subjective scales SSTICS and cognitive tests completed online using Millisecond softwares. Subjective well-being under antipsychotics will be assessed by means of the SWN-SF.
7. Global and social functioning will be assessed using the GAF, the PSP total score and the EPHP (rated by the caregivers). Quality of life will be assessed using the S-QoL and the EQ-5D-5L (EuroQoL-5D) and the recovery process by means of the Questionnaire about the Process of Recovery (QPR).
8. The influence of specific patient characteristics on our primary outcome will be assessed, in particular, the level of interaction between treatment intervention and phenotype and: a) the history of psychotic episodes (i.e. patients with first or multiple psychotic episode(s)) b) the presence/absence of current substance abuse disorder (this will not represent an exclusion criteria); similar to Radar and Hamlett studies.
9. Practically, if a patient presents with a transient increase of psychotic symptoms during a step X of the DR schema, we will estimate that the individual minimal effective dose (i-MinED) is that corresponding to the dose given during the previous step (X-1) in the DR protocol.
10. Significant relapse and PSP, 3 months after reaching the MinED.
11. Mean antipsychotic dosage at study endpoint in each arm (as expressed in eqOlz and in % of D2-R occupancy)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 14

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Les Hopitaux Universitaires De Strasbourg

Sponsor organisation

Les Hopitaux Universitaires De Strasbourg

Address

1 Place De L Hopital, Cs 80426 Cs 80426

City

Strasbourg Cedex

Postcode

67091

Country

France

Scientific contact point

Organisation

Les Hopitaux Universitaires De Strasbourg

Contact name

Pr. Fabrice BERNA

Public contact point

Organisation

Les Hopitaux Universitaires De Strasbourg

Contact name

Mrs. Sarah HUSTACHE

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 48 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications