Cerebrovascular Reactivity to Nitrous Oxyde in Resistant Depression: the PROTOBRAIN Pilote Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Brain Tissue Pulsatility (BTP) as measured with Ultrasound TPI
研究概览
简要总结
Recent evidence suggest that Nitrous Oxyde (N2O) could exhibit antidepressant effect in treatment-resistant depression (TRD). However, the pathophysiology of this effect remains unclear and could include glutamatergic activity but also cerebrovascular effects and changes in brain connectivity. The goal of our study is to characterize brain reactivity to N2O in TRD patients, as assessed with Ultrasound Tissue Pulsatility Imaging (TPI) and Magnetic Resonance Imaging (MRI) (including Arterial Spin Labeling - ASL - for brain perfusion and Blood-Oxygen-Level Dependent - BOLD - for brain connectivity and pulsatility).
Ultrasound and MRI Neuroimaging will be measured before, during and after a single one-hour exposure of a 50%N20/50%O2 mixture, in depressed individuals (n=20) and healthy volunteers (n=10). We make the hypothesis that brain reactivity will be lower in depressed individuals nonresponders to N2O compared to responders and healthy controls. This study would provide further characterisation of the pathophysiology of the antidepressant response to N2O, as well as providing potential biomakers (Ultrasound and MRI) for treatment response to N2O in TRD.
详细描述
Neuroimaging examinations will include:
- Ultrasound Tissue Pulsatility Imaging for assessment of Brain Tissue Pulsatility (BTP) which reflects reactivity in brain movements and mechanical brain properties
- MRI with structural and functional assessments, namely brain volumes, white matter lesions, ASL for brain perfusion and BOLD for resting-state connectivity and brain pulsatility
MRI will be performed before and after a single one-hour exposure of 50%N2O/50%O2 mixture. Ultrasound will be performed before, after and also during gas exposure. Changes in these neuroimaging parameters will constitute the primary assessment of the study. Psychometric and safety assessements will complete the neuroimaging outcomes.
Follow-up will includes 1) a baseline visit for baseline MRI and Psychometric assessements, 2) a second visit for gas exposure and neuroimaging assessements, 3) a third and fourth visits for psychometric and safety assessements, respectively 24 hours and one week after gas exposure.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 25 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Inclusion criteria common to all participants
- •Female between 25 and 50 years of age
- •A person who can undergo N2O diffusion via a facial mask.
- •A person who has signed an informed consent.
- •Person affiliated with a social security scheme.
- •Inclusion Criteria for Depressive Patients
- •Major Depressive Episode according to DSM-5 criteria, confirmed by the MINI - International Neuropsychiatric Interview.
- •Patients with an MADRS score greater than 20 (Montgomery
- •Asberg Depression Rating Scale).
- •Patients resistant to at least one well-conducted antidepressant treatment, as documented by the MGH-ATRQ scale.
- •Absence of: bipolar disorder, schizophrenic disorder, neurodegenerative disease, schizophrenic disorder, neurodegenerative disease, addiction to one or more toxics documented by the MINI.
- •Inclusion criteria for healthy voluntary controls
- •Absence of: bipolar disorder, schizophrenic disorder, neurodegenerative disease, schizophrenic disorder, neurodegenerative disease, addiction to one or more toxics documented by the MINI, current or past.
排除标准
- •Unstable somatic pathology (including unstable neurological or cardiological pathologies at risk of interfering with N2O diffusion)
- •Presence of active and significant psychotic symptoms, at investigator's discretion
- •Contraindications to mixture 50%N2O/ 50%O2: intracranial hypertension, altered state of consciousness, head trauma, pneumothorax, emphysema bubbles, abdominal gaseous distension, administration of less than 3 months of ophthalmic gas (SF6, C3F8,C2F6) used in eye surgery, known and unsubstituted deficiency in vitamin B12 or folic acid, recent and unexplained neurological abnormalities.
- •Contraindications to MRI, including claustrophobia.
- •Female who is pregnant or breastfeeding or able to procreate without an effective contraceptive method
- •Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, purpose or consequences of the study (including major under legal protection).
- •A person participating in a drug clinical trial or during a period of exclusion from any clinical study due to previous involvement.
研究组 & 干预措施
healthy voluntary controls
A single Non-blinded One-hour administration of 50% Nitrous oxyde (N2O) 50%oxygen (O2) Gas Mixture
干预措施: Nitrous Oxide-Oxygen (Drug)
healthy voluntary controls
A single Non-blinded One-hour administration of 50% Nitrous oxyde (N2O) 50%oxygen (O2) Gas Mixture
干预措施: Tissue Pulsatility Imaging - TPI (Device)
healthy voluntary controls
A single Non-blinded One-hour administration of 50% Nitrous oxyde (N2O) 50%oxygen (O2) Gas Mixture
干预措施: Magnetic Resonance Imaging - MRI (Device)
Depressive Patients
A single Non-blinded One-hour administration of 50% Nitrous oxyde (N2O) 50%oxygen (O2) Gas Mixture
干预措施: Nitrous Oxide-Oxygen (Drug)
Depressive Patients
A single Non-blinded One-hour administration of 50% Nitrous oxyde (N2O) 50%oxygen (O2) Gas Mixture
干预措施: Tissue Pulsatility Imaging - TPI (Device)
Depressive Patients
A single Non-blinded One-hour administration of 50% Nitrous oxyde (N2O) 50%oxygen (O2) Gas Mixture
干预措施: Magnetic Resonance Imaging - MRI (Device)
结局指标
主要结局
Brain Tissue Pulsatility (BTP) as measured with Ultrasound TPI
时间窗: 3 months after LVLS
BTP will be measured before, during and after N2O exposure
次要结局
- STAI-Y-A - State-Trait Anxiety Inventory(6 months after LVLS)
- YMRS - Young Mania Rating Scale(6 months after LVLS)
- BPRS - Brief Psychiatric Rating Scale(6 months after LVLS)
- White Matter Lesions (MRI)(6 months after LVLS)
- Resting-State Connectivity (BOLD-MRI)(6 months after LVLS)
- Brain Pulsatility (BOLD-MRI)(6 months after LVLS)
- CGI - Clinical Global Impressions(6 months after LVLS)
- Brain Volumes (MRI)(6 months after LVLS)
- Brain Perfusion in Arterial Spin Labelling (ASL-MRI)(6 months after LVLS)
- Hamilton scale for depression, 17-items(6 months after LVLS)
- POMS - Profile of Mood State(6 months after LVLS)
- QIDS-SR - Quick Inventory of depressive Symptomatology Self Report(6 months after LVLS)
- subjective VAE- Visual Analog Evaluation(6 months after LVLS)
- SSI - Scale for Suicidal Ideation(6 months after LVLS)
- CADSS - Clinician administered dissociative States(6 months after LVLS)