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
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 288
- 试验地点
- 1
- 主要终点
- 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).
研究概览
简要总结
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).
研究设计
- 分配方式
- Randomized
- 主要目的
- First and only period
- 盲法
- Single (Analyst)
入排标准
- 年龄范围
- 18 years 至 64 years（18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Patient 18-60 years of age;
- •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 <
- •Patient treated with oral antipsychotics (in mono or polytherapy, with second- or first-generation antipsychotics);
- •Patients with a PSP score >70 at baseline
- •Patient affiliated to health insurance (beneficiary or beneficiary’s family);
- •Patient informed of the results of the preliminary medical examination;
- •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.
- •Informed consent signed by patient (with assistance of his/her curator, if applicable (if subject under curatorship*))
- •Patient with a diagnosis of schizophrenia spectrum disorder (SSD): schizophrenia, schizophreniform, schizoaffective disorder or brief psychotic episode according to DSM-5;
- •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%)
- •Outpatient followed by an ambulatory psychiatrist;
- •Patient with an identified caregiver
排除标准
- •Patient hospitalized in a psychiatric ward;
- •Patient in an exclusion period defined by another research protocol;
- •Patient under guardianship (i.e. French ‘tutelle’);
- •Patient with care under constraint
- •Patients deprived of freedom because of a judicial measure.
- •Inability to give the patient the written consent form (emergency situation)
- •Patient with a recent psychotic episode (during the last 6 months);
- •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);
- •Patient treated with clozapine (in mono or polytherapy – highly resistant patients, specificities of the relapses under clozapine (Luykx et al., 2020));
- •Patient considered by his psychiatrists to be at serious risk of harm to self or others (e.g. previous aggressive or suicidal behaviors);
- •Neurological or severe medical condition other than psychosis;
- •Pregnancy (verified by urinary test at enrollment for women of childbearing age);
- •Current breastfeeding;
- •Patient involved in another Investigational Medicinal Product trial;
结局指标
主要结局
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).
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).
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.
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.
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.
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.
次要结局
- 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.
- 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).
- A relapse will be defined by either as: a) a new hospitalization due to exacerbation of symptoms b) aggressive behavior c) suicidal attempt
- 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
- 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.
- 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.
- 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).
- 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.
- 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.
- Significant relapse and PSP, 3 months after reaching the MinED.
- Mean antipsychotic dosage at study endpoint in each arm (as expressed in eqOlz and in % of D2-R occupancy)
研究者
Pr. Fabrice BERNA
Scientific
Les Hopitaux Universitaires De Strasbourg