Combining Hedonic Olfactory and BRAin Stimulations in Treatment-resistant Depression
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- Change in MADRS score before and after intervention to characterized the number of depressed patients who reach remission criteria (MADRS ≤ 10) in each group
研究概览
简要总结
This is a prospective, randomized, double-blind, parallel-group controlled trial. The aim of this research project is to compare the clinical benefits achieved in patients with major depressive disorder (MDD) following two types of intervention: iTBS active alone or iTBS active combined with olfactory stimulations.
详细描述
Major depressive disorder (MDD) is the most widespread psychiatric disorder, affecting 5% of adults according to the World Health Organization. Anhedonia, defined as the loss of the ability to experience pleasure, is one of the key symptoms of depression, possibly due to a dysfunction of the reward system. Intermittent theta-burst stimulation (iTBS) targeting the dorsolateral prefrontal cortex (DLPFC) has been demonstrated as an emerging treatment option for treatment-resistant depression. One explanation is that iTBS could work through modulating the reward system (increasing dopamine release). One way to improve the therapeutic benefits of non-invasive brain stimulation is to combine it with other therapeutic strategies. Interestingly, olfactory training -daily short-term exposure to pleasant odors- improves significantly depressive symptoms in MDD patients. Indeed, the olfactory system and the reward system are closely related through the olfactory tubercle, which is in the ventral striatum and directly connected to the ventral tegmental area.
The general aim of this research project is to test whether a combination of iTBS targeting the left DLPFC with an olfactory training can improve treatment outcome in MDD, compared to iTBS targeting the left DLPFC alone.
The investigators hypothesize that combining iTBS treatment on DLPFC with hedonic olfactory stimulation potentiates the effect of iTBS treatment administered alone on depressive symptoms, especially anhedonia (physical, social or olfactory). Moreover, the investigators also hypothesize that the superiority of the combined approach is underpinned by greater modulation of connectivity activity and strength between brain regions involved in dopaminergic transmission, compared with iTBS alone.
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Patients will be block randomized (1:1) to receive either iTBS active combined with an olfactory stimulation or TBS active alone. Computer generated random numbers will be used to generate the allocation sequence. The allocation sequence will be handled by an independent person from the Administrative Department of the Hospital and will be unavailable to those who enroll and assign patients. Patients will be blind to their treatment assignment. Moreover, the medical doctors who will administer the clinical scales and the researchers that will analyze the data will be blinded to the allocation.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •had a primary diagnosis of single-episode or recurrent non-psychotic major depressive disorder according to Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) criteria;
- •scored 20 or over on the MADRS (Montgomery-Åsberg Depression Rating Scale) (Montgomery and Åsberg, 1979) and scored higher than 2 on the MADRS item 8 anhedonia factor score;
- •a stable antidepressant medication for 4 weeks prior to inclusion; be able to speak and read French;
- •sign a consent form before intervention.
排除标准
- •a pre-existing condition that affects olfaction including congenital anosmia, upper respiratory tract infection, nasal and/or sinus disease, brain injury or nasal surgery; a neurological disease;
- •other comorbid psychiatric disorders or substance abuse (except tobacco);
- •contraindications to TMS (medical devices implanted or metallic foreign body in the head);
- •pregnant or lactating mothers (controlled by urine pregnancy tests);
- •measure of protection or guardianship of justice.
结局指标
主要结局
Change in MADRS score before and after intervention to characterized the number of depressed patients who reach remission criteria (MADRS ≤ 10) in each group
时间窗: 4 times : before the Intervention (J0), immediately following the end of the Intervention (J15), 1 (M1) and 3 months (M3) after the end of the Intervention.
MADRS is a clinician-rated scale designed to measure depression severity and detect changes due to intervention. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition. Remission is defined as a Montgomery and Asberg Depression Rating Scale (MADRS) score less than or equal to 10 at the end of 50 sessions of iTBS
次要结局
- Group differences in functional connectivity changes in the targeted brain network(2 times : before the Intervention (J0), immediately following the end of the Intervention (J15))
- Group differences in Beck Depressive Inventory (BDI) score changes(4 times : before the Intervention (J0), immediately following the end of the Intervention (J15), 1 (M1) and 3 months (M3) after the end of the Intervention.)
- Group differences in European Test of Olfactory Capabilities (ETOC) score changes(2 times : Before the Intervention (J0), immediately following the end of the Intervention (J15))
- Group differences in the Chapman Social Anhedonia Scale (SAS)(4 times : before the Intervention (J0), immediately following the end of the Intervention (J15), 1 (M1) and 3 months (M3) after the end of the Intervention.)
- Group differences in conditioned motor evoked potential (MEP) peak-to-peak amplitude changes(2 times : before the Intervention (J0), immediately following the end of the Intervention (J15))
- Group differences in the Childhood Trauma Questionnaire (CTQ) score changes(1 time : Before the Intervention (J0))
- Group differences in Montgomery-Asberg Depression Rating Scale (MADRS) score changes(4 times : Before the Intervention (J0), immediately following the end of the Intervention (J15), 1 (M1) and 3 months (M3) after the end of the Intervention.)
- the Chapman Physical Anhedonia Scale (PAS) score changes(4 times : before the Intervention (J0), immediately following the end of the Intervention (J15), 1 (M1) and 3 months (M3) after the end of the Intervention.)