Targeting Inflammation in Depression Using Minocycline: a Patient Stratification Approach Using Peripheral Inflammatory Biomarkers, PET and MRI
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Changes from baseline in the peripheral inflammatory status assessed by the measurement of CRP levels and inflammatory markers (i.e. IL-1, IL-6, IL-17 and TNF-alpha)
研究概览
简要总结
The study aims to evaluate or to assess:
- An improvement in the peripheral inflammatory levels in depressed patients after 8 weeks of treatment with Minocycline in addition to their current antidepressant treatment;
- Any improvements in depressive symptoms after 8 weeks of treatment with Minocycline given as adjuvant to the current antidepressant treatment;
- Changes in the inflammatory status in the brain (in terms of microglia activation with 11C PK PET) after 8 weeks of treatment with Minocycline in addition to the current patient's treatment;
- Possible structural and functional brain changes evaluated by MRI after 8 weeks of treatment with Minocycline given as adjuvant to the current patient's treatment;
- Whether changes in MRI, in microglia activation, and peripheral inflammation correlate with the improvement in depressive symptoms.
In order to achieve these, a total of 60 patients, male and female, aged 25-45, who have not responded to their pharmacological treatment and who have medium-high levels of inflammation (with CRP> 2 mg/L) will be included in the study.
Enrolled patients will receive, in addition to their current antidepressant treatment, Minocycline (200 mg/day as total dosage) for 8 weeks.
Patients will be subjected to blood collection and clinical evaluations at baseline and after 8 weeks of treatment with Minocycline.
A subgroup of patients will be subjected to MRI and 11C PK PET assessment at baseline and after 8 weeks of treatment with Minocycline.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 25 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Being male or female depressed patients (aged 25-45);
- •Having a current DSM-V diagnosis of non-psychotic major depressive disorder confirmed by SCID;
- •Being non-responder to a current SSRI for at least 8 weeks, and historically to one other SSRI;
- •Being in stable antidepressant therapy for at least 8 weeks;
- •Being tolerant to the current SSRI;
- •Accepting Minocycline treatment;
- •Having CPR level> 2 mg/L;
- •Having signed and dated an informed consent to participate in the study;
- •Having no contraindications to receive treatment with Minocycline;
- •Having no contraindications to undergo the 11C-PK PET scan.
排除标准
- •Having active suicidal ideation;
- •Having a primary diagnosis of bipolar disorder, obsessive-compulsive disorder, eating disorder, PTSD;
- •Having a history of substance/alcohol abuse;
- •Having received tetracycline therapy within the previous 2 months;
- •Having a history of sensitivity to this class of drugs;
- •Having acute infections or an autoimmune or inflammatory disorder;
- •Having CRP>20 mg/L, as indicates acute infection or other major pathology;
- •Being sensitive to Minocycline;
- •Having a history of severe allergy or hypersensitivity to drugs;
- •Being hypersensitive to the active substance, to other tetracyclines or to any of the excipients;
- •Having severe renal failure;
- •Having hepatic dysfunction;
- •Being pregnant and in lactation;
- •(for MRI) Having pacemakers, electromechanical devices, ferromagnetic vascular clips, cochlear implants, stapedial prostheses, ferromagnetic foreign bodies, sickle cell anemia;
- •EXCLUSION CRITERIA (FOR ONLY THOSE PATIENTS WHO WILL PERFORM 11C PK PET)
- •Having undergone imaging or treatment procedures using radiopharmaceuticals 7 days prior to the imaging session of this study;
- •Being unable to complete the 11C PK PET session, according to the clinician;
- •Being in current or previous (last two months) treatment with neuroactive drugs (benzodiazepines, barbiturates, picrotoxin and muscimol);
- •Being women of childbearing potential who are not surgically sterile and who do not guarantee to abstain from sexual activity for the 24 hours following the administration of 11C PK PET.
研究组 & 干预措施
Minocycline
All subjects will receive Minocycline over 8 weeks in addition to their current antidepressant treatment.
干预措施: Minocycline (Drug)
结局指标
主要结局
Changes from baseline in the peripheral inflammatory status assessed by the measurement of CRP levels and inflammatory markers (i.e. IL-1, IL-6, IL-17 and TNF-alpha)
时间窗: Changes from baseline to week 8
To evaluate an improvement in the peripheral inflammatory status in depressed patients after 8 weeks of treatment with Minocycline in addition to their current pharmacological treatment.
次要结局
- Changes from baseline of the associations among brain structure observed with MRI, activation of microglia by PET, peripheral inflammatory markers and depression assessment scales(Changes from baseline to week 8)
- Change from baseline in depressive symptoms assessed by HAM-D17(Changes from baseline to week 8)
- Structural and functional brain changes by MRI(Changes from baseline to week 8)
- Changes from baseline in central inflammatory levels by PET and by assessing differences in PK11195 binding(Changes from baseline to week 8)
研究者
Annamaria Cattaneo
PhD, Lab head of Biological Psichiatry Unit
IRCCS Centro San Giovanni di Dio Fatebenefratelli