Stratifying Psychoses for Personalized REpetitive TMS in Persistent NEgative Symptoms Alleviation
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 160
- 主要终点
- Decrement in positive and negative syndrome scale - negative sub-score (ΔPANSS-N).
研究概览
简要总结
In its 2012's release guideline on therapy for schizophrenia, the EMA joined the FDA to acknowledge primary and persistent negative symptoms (PNS) as an unmet need in the treatment of schizophrenia. Functional brain imaging studies showed a correlation between NS and reduced perfusion in the left dorsolateral prefrontal cortex (L-DLPFC). Pre-frontal activation (PFA) using repetitive transcranial magnetic stimulation (rTMS) significantly improve PNS (meta-analyses: effect size SMD = 0.55, ΔPANSS-N = -2.5). Yet schizophrenia is likely to gather many different natural entities of distinct pathophysiological mechanisms. Pursuing a one-size-fits-all approach will not adapt to this diversity and might account for inconsistencies in the results.
Progressive periodic catatonia (PPC) is a rare psychotic phenotype (0.1 - 0.5 ‰) which has been shown to be longitudinally stable (30-years follow-up) and consistent within families (about 1 third of first-degree relatives are affected). The core of this phenotype is a disintegration of psychomotor processes which progresses with each relapse, resulting in a "deficit state", i.e., PNS, responsible for most social and occupational disabilities. The investigators and others reported PPC to come with hyper-perfusions in premotor cortices compared to controls or non-PPC chronic psychoses (nPPC). These hyper-perfusions discriminate PPC from nPPC or depressive patients (Sensitivity = 82%; Specificity = 95%). Last, in independent proof-of-principle studies the investigators and others have shown that premotor inhibition (PMI) using rTMS significantly improved PNS in PPC and that the most dramatic improvements followed personalized accelerated rTMS protocols (5 days of rTMS; CGI-improvement = 2 which is equivalent to ΔPANSS-N = -10; lasting > 1 month - vs virtually no change for PFA). The efficacy index was very good (no side effects).
the investigators hypothesize that: (1) in PPC, add-on personalized premotor inhibition (PMI) is more effective in reducing PNS than L-DLPFC activation (PFA); (2) patient stratification is relevant as personalized PMI will not be as effective in the nPPC group (even expected to be less effective than PFA).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Informants (caregivers)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18-70 years of age; affiliated to health insurance; superior or equal to B2 level of linguistic competency in French.
- •Suffering from schizophrenia spectrum disorder (SSD) in residual state with persistent negative symptoms (PNS): (1) SSD: ICD-11 codes beginning with 6A2 + primary catatonia (codes beginning with 6A4) + simple schizophrenia as defined in ICD-10 (F20.6); (2) PNS: persistence (≥6 months - based on patient ± informant's interview) of ≥2 negative symptoms (PANSS-N1, N2, N3, N4, N6 ≥4) with functional impact.
- •Half of subjects having PPC, the other half suffering from another phenotype or nPPC (neuropsychiatric procedure or probabilistic, i.e. Bayes-PPC).
- •Under a stable medication regimen for >6 weeks,
- •Subjects who have received the protocol information and signed informed consent.
排除标准
- •- Contraindications for MRI or rTMS.
- •Motor deficit at neurological examination.
- •Secondary negative symptoms: (1) withdrawal secondary to severe anxiety (especially due to positive symptoms), (2) depression, (3) maintenance on high dose antipsychotics, (4) extra-pyramidal or (5) sedation side-effects, (6) treatment non-compliance, (7) current substance abuse (except nicotine and caffeine), (8) unsubstituted past opioid addiction, (9) poor health or social condition.
- •Under antiepileptic drugs (except lamotrigine and long-term use of benzodiazepines).
- •Pregnancy; severe medical condition; care under constraint.
结局指标
主要结局
Decrement in positive and negative syndrome scale - negative sub-score (ΔPANSS-N).
时间窗: Pre-rTMS and end-of-trial (before - week 4, and 6 weeks after rTMS - week12).
Positive and negative syndrome scale - negative sub-score ΔPANSS-N = ΔN1 + ΔN2 + ΔN3 + ΔN4 + ΔN6 PMI personalized rTMS superiority claim in PPC: ANOVA within-between 2 factors interaction (two-way comparison): * The within factor is "pre-rTMS/end-of-study", i.e., PNS change between the 2 repeated measures: PANSS-N before and at 1.5-months after rTMS. * The between factor is "treatment arm": PMI vs PFA. Precision medicine claim (phenotype-dependent response): 3-way ANOVA (interaction between the 2 between and 1 within factors): * The within factor is "pre/end", i.e., PNS change between the 2 repeated measures: PANSS-N before and at 1.5-months after rTMS. * The first between factor is "treatment arm": PMI vs PFA. * The second between factor is "phenotype": PPC vs nPPC.
次要结局
未报告次要终点