Evaluating the Antidepressant Efficacy of Transcranial Magnetic Stimulation (TMS) in Patients With Inflammatory Bowel Disease (IBD) and Effects on IBD-related Symptoms.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Change in depressive and anxiety symptoms with active iTBS-rTMS as compared to sham treatment group
研究概览
简要总结
Transcranial magnetic stimulation (rTMS) has demonstrated diagnostic and therapeutic potential for a number of conditions and is an approved treatment for depression. Inflammatory Bowel Disease (IBD) has a significant impact on mental health, and comorbid maladaptive behaviors and pain are highly prevalent in patients with IBD and are often under-treated.
The investigators predict TMS will improve comorbid maladaptive behavior (heightened interoceptive awareness, sleep, fatigue, catastrophizing, anxiety and depression), reduce pain and improve quality of life in persons with inflammatory bowel disease (IBD). Further, TMS benefits will be associated with changes in gut microbiome as measured by stool, blood and urine samples and normalization of IBD-associated changes in brain structure and/or function as measured by magnetic resonance imaging (MRI).
详细描述
Background and rationale:
Comorbid maladaptive behaviors and pain are highly prevalent in patients with IBD and are often under-treated. These comorbidities lack effective therapies and thus complicate medical management, adversely impact patient outcome and health, and increase the resource burden on the healthcare system. Development of effective treatment delivery is therefore vital. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive form of brain stimulation in which an electric pulse generator placed at the scalp produces a rapidly changing magnetic field at biologically relevant frequencies to induce a stimulating electrical current at targeted sites in the brain. rTMS has demonstrated diagnostic and therapeutic potential for a number of conditions, including Alzheimer's disease, autism, bipolar disorder, epilepsy, chronic pain, major depressive disorder, Parkinson's disease, post-traumatic stress disorder (PTSD), schizophrenia (negative symptoms), obsessive-compulsive disorder (OCD), and for the cessation of smoking. To date, however, rTMS has not been used to treat the mental health issues and symptoms observed in persons with IBD. The investigators will develop rTMS interventions for IBD to target comorbid maladaptive behaviors and pain using evidence-based knowledge of TMS effectiveness for other chronic medical conditions.
Research Question:
Compared to sham, does twice daily intermittent theta-burst stimulation rTMS delivered to the left dorsolateral prefrontal cortex for two weeks (20 sessions) improve comorbid maladaptive behavior (heightened interoceptive awareness, sleep, fatigue, catastrophizing, anxiety and depression), reduce pain and improve quality of life in persons with inflammatory bowel disease (IBD)? Further, will TMS benefits be associated with changes in gut microbiome and normalization of IBD-associated changes in brain structure and/or function as measured by magnetic resonance imaging (MRI)?
Methods:
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)
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
- •confirmed diagnosis of IBD, demonstrated to be in endoscopic remission (Mayo Endoscopic Subscore [for UC] 0 or 1, or Simple Endoscopic Score for CD ≤4) or biomarker remission (fecal calprotectin <250 ug/g) within 6 months of randomization
- •≥8 on the Hospital Anxiety and Depression Scale
- •on stable IBD-related and psychotropic medications for the four weeks preceding randomization
排除标准
- •severely active IBD (Mayo score > 9, HBI > 16)
- •require systemic corticosteroids
- •initiated biologic treatment within the preceding three months
- •suicidal ideation
- •psychosis
- •having failed ECT
- •previous rTMS treatment (for blinding integrity)
- •contraindications for MRI
- •Use of benzodiazepines or GABA agonists
结局指标
主要结局
Change in depressive and anxiety symptoms with active iTBS-rTMS as compared to sham treatment group
时间窗: Measured at baseline, halfway through rTMS treatment (week 1), end of rTMS treatment (week 2) and 4 weeks post treatment (week 6)
Hospital Anxiety and Depression Scale (HADS) will be used to assess anxiety and depression. The HADS questionnaire has seven items each for depression and anxiety subscales. Scoring for each item ranges from zero to three, with three denoting highest anxiety or depression level. A total subscale score of \>8 points out of a possible 21 denotes considerable symptoms of anxiety or depression.
次要结局
- Change in IBD symptoms with active iTBS rTMS compared to sham rTMS(Measured at baseline, halfway through rTMS treatment (week 1), end of rTMS treatment (week 2) and 4 weeks post treatment (week 6))
- Change in self reported physical, mental and social health and well-being in persons with IBD with active iTBS rTMS compared to sham rTMS(Measured at baseline, halfway through rTMS treatment (week 1), end of rTMS treatment (week 2) and 4 weeks post treatment (week 6))
- Stool samples- Individual microbial analysis(Stool will be collected at baseline, at the conclusion of the 2 week double-blind phase, and at 4 weeks post treatment (week 6))
- Magnetic Resonance (MR) spectroscopy(Subjects will undergo MRI at 0 (baseline) and at the completion of the blinded phase (week 2))
- Change in self reported anxiety symptoms in persons with IBD with active iTBS rTMS compared to sham rTMS(Measured at baseline, halfway through rTMS treatment (week 1), end of rTMS treatment (week 2) and 4 weeks post treatment (week 6))
- Change in self reported symptoms of gastrointestinal pain in persons with IBD with active iTBS rTMS compared to sham rTMS(Measured at baseline, halfway through rTMS treatment (week 1), end of rTMS treatment (week 2) and 4 weeks post treatment (week 6))
- Change in quality of sleep with active iTBS rTMS compared to sham rTMS in persons with IBD.(Measured at baseline, halfway through rTMS treatment (week 1), end of rTMS treatment (week 2) and 4 weeks post treatment (week 6))
- Change in self reported fatigue in persons with IBD with active iTBS rTMS compared to sham rTMS(Measured at baseline, halfway through rTMS treatment (week 1), end of rTMS treatment (week 2) and 4 weeks post treatment (week 6))
- Magnetic Resonance Imaging (MRI)- White matter imaging(Subjects will undergo MRI at 0 (baseline) and at the completion of the blinded phase (week 2))
- Change in depressive symptoms as measured by Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to week-2 (post rTMS treatment) with iTBS-rTMS as compared to sham treatment group(Measured at baseline, halfway through rTMS treatment (week 1), end of rTMS treatment (week 2) and 4 weeks post treatment (week 6))
- Change in mood from baseline to week 2 (post rTMS treatment) with iTBS-rTMS as compared to sham treatment group(Measured at baseline, halfway through rTMS treatment (week 1), end of rTMS treatment (week 2) and 4 weeks post treatment (week 6))
- Change in self reported depressive symptoms in persons with IBD with active iTBS rTMS compared to sham rTMS as measured by the Patient Health Questionaire.(Measured at baseline, halfway through rTMS treatment (week 1), end of rTMS treatment (week 2) and 4 weeks post treatment (week 6))
- Change in interoceptive awareness with active iTBS rTMS compared to sham rTMS in persons with IBD.(Measured at baseline, halfway through rTMS treatment (week 1), end of rTMS treatment (week 2) and 4 weeks post treatment (week 6))
- Change in cognitive function with active iTBS rTMS compared to sham rTMS in persons with IBD.(tests will also be administered at baseline and at the conclusion of the 2 week double-blind phase, and at 4 weeks post treatment (week 6))
- Functional Magnetic Resonance Imaging (fMRI)(Subjects will undergo MRI at 0 (baseline) and at the completion of the blinded phase (week 2))
- Magnetic Resonance Imaging (MRI)- Volumetric imaging.(Subjects will undergo MRI at 0 (baseline) and at the completion of the blinded phase (week 2))
- Change in quality of life in persons with IBD with active iTBS rTMS compared to sham rTMS(Measured at baseline, halfway through rTMS treatment (week 1), end of rTMS treatment (week 2) and 4 weeks post treatment (week 6))
- Change in self reported depressive symptoms in persons with IBD with active iTBS rTMS compared to sham rTMS as measured by the Quick Inventory of Depressive Symptomatology(Measured at baseline, halfway through rTMS treatment (week 1), end of rTMS treatment (week 2) and 4 weeks post treatment (week 6))
- Stool samples- Microbial community measurements(Stool will be collected at baseline, at the conclusion of the 2 week double-blind phase, and at 4 weeks post treatment (week 6))
- Magnetic Resonance Imaging (MRI)- Inflammation imaging.(Subjects will undergo MRI at 0 (baseline) and at the completion of the blinded phase (week 2))
- Change in catastrophizing thoughts and feelings in persons with IBD with active iTBS rTMS compared to sham rTMS(Measured at baseline, halfway through rTMS treatment (week 1), end of rTMS treatment (week 2) and 4 weeks post treatment (week 6))
- 16S and ITS2 rRNA gene sequencing.(Stool, urine, and blood samples will be collected at baseline, at the conclusion of the 2 week double-blind phase, and at 4 weeks post treatment (week 6))
- Implicit Suicidal Thoughts(tests will also be administered at baseline, at the conclusion of the 2 week double-blind phase, and at 4 weeks post treatment (week 6))