Observational Study to Investigate the Effect of White Matter Tract Distortion and Neurodegenerative Biomarkers on Shunt-responsiveness in Idiopathic Normal Pressure Hydrocephalus (iNPH)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- White Matter Pathway Diffusion Metrics
研究概览
简要总结
Idiopathic Normal Pressure Hydrocephalus (iNPH) is a progressive condition of the elderly that results in severe disability. iNPH can dramatically respond to Cerebral spinal fluid(CSF)-shunting where excess ventricular fluid is diverted from the brain. Not all patients with iNPH respond to CSF-shunting however. The reasons for this are uncertain.
Aim 1: To understand if specific nerve pathways (white matter tracts) that are near ventricles are damaged in patients that respond to shunting as opposed to those that do not.
Aim 2: Can we explain shunt non-responsiveness by screening for dementia like illnesses (neurodegeneration) using a large array of methods.
Aim 3: To understand whether wearable activity and bed sleep monitors are palatable in a NPH population and to understand if these metrics relate to quality of life.
Aim 4: To see whether self-administered digital cognitive assessments can measure improvements pre and post surgery.
详细描述
This single-centre observational cohort study will follow 50 patients diagnosed with symptomatic Normal Pressure Hydrocephalus (NPH) (idiopathic or late presenting congenital hydrocephalus and not secondary hydrocephalus) through their clinical journey, from initial assessment to post-CSF shunt surgery or a time when surgery is decided against. Separate groups of 50 asymptomatic individuals with chronic hydrocephalus and non-hydrocephalus individuals will act as controls.
Participants will undergo comprehensive clinical assessments including gait, cognitive and urinary evaluations, quality of life measures, serum and CSF degenerative biomarker analysis, diffusion-weighted Magnetic Resonance Imaging (MRI) and optional brain and skin biopsies. Data collection will focus on capturing changes in clinical presentation and imaging findings before and after shunting. REDCap will be utilised as the primary tool for data storage.
Primary outcome measures assess pre and post-shunting imaging changes in shunt-responders and non-responders. Shunt response will be defined as 10% improvement in gait speed. Secondary outcomes evaluate the relationship between biomarkers and clinical outcomes. Longitudinal data will help identify factors distinguishing responders from non-responders, with descriptive and inferential statistics used.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adult patients >60
- •With gait apraxia
- •With or without cognitive impairment
- •Urinary dysfunction
- •Communicating Hydrocephalus
排除标准
- •Asymptomatic hydrocephalus
- •High pressure-hydrocephalus
- •Serious head injury within 5 years of presentation or a clear secondary cause (e.g. brain infection)
- •History of childhood gait disturbance
- •Clear alternative explanation for symptoms (e.g. Parkinson's disease with limb rigidity, peripheral neuropathy with sensory ataxia, cervical myelopathy).
- •Too frail for shunt surgery
- •Medically unstable (e.g. active angina, respiratory disease, recurrent delirium, active epilepsy).
- •Unable to tolerate MRI brain imaging
- •Unable to have a lumbar puncture
- •Unable to attend the hospital for study visits
- •Group 2 (asymptomatic and non-hydrocepahlus dementia and healthy controls):
- •Inclusion Criteria (Any of the following):
- •Healthy Carers
- •Members of the Public
- •Staff of Imperial College/ICHT
- •Non-NPH Dementias (including Alzheimer's disease or vascular dementia)
- •Asymptomatic Hydrocephalus
- •Exclusion Criteria:
- •Unable to attend the hospital for study visits
结局指标
主要结局
White Matter Pathway Diffusion Metrics
时间窗: Perioperative
Change from baseline in diffusion tensor imaging (DTI) metrics of white matter pathways (e.g. FA, AD, RD) before and after shunt surgery. The following tracts will be studied: corpus collosum, internal capsule, corona radiata and anterior thalamic radiation.
次要结局
- Neurodegenerative Biomarkers and CSF-shunt responsiveness(Perioperative)
- Serum Neurodegenerative Biomarkers(From enrolment, at periprocedural and up to 27 weeks)
- Sleep Monitoring(From enrolment and through study completion, an average of 1 year)
- Activity Monitoring(From enrolment and through study completion, an average of 1 year)
- Tinetti Performance Oriented Mobility Assessment Score (balance)(From enrolment, at periprocedural and up to 27 weeks)
- Tinetti Performance Oriented Mobility Assessment Score (Gait)(From enrolment, at periprocedural and up to 27 weeks)
- Addenbrooke's Cognitive Examination ||| (ACE-|||)(From enrolment, at periprocedural and up to 27 weeks.)
- International Consultation on Incontinence Questionnaire for Urinary Incontinence Short Form (ICIQ UI SF)(From enrolment, at periprocedural and up to 27 weeks.)
- International Consultation on Incontinence Questionnaire for Bowels (ICIQ-B)(From enrolment, at periprocedural and up to 27 weeks.)
- International Consultation of Incontinence Questionnaire for Sexual Function(From enrolment, at periprocedural and up to 27 weeks.)
- International Consultation of Incontinence Questionnaire for Quality of Life(From enrolment, at periprocedural and up to 27 weeks.)
- Overactive Bladder Symptoms (OAB)(From enrolment, at periprocedural, and up to 27 weeks.)
- Kubo scale(From enrolment, at periprocedural and up to 27 weeks.)
- Patient Health Questionnaire-9 (PHQ-9)(From enrolment, at periprocedural and up to 27 weeks.)
- Sintonen 15D(From enrolment, at periprocedural and up to 27 weeks.)
- PSP QoL(From enrolment, at periprocedural and up to 27 weeks.)
- Generalised Anxiety Disorder-7 (GAD-7)(From enrolment, at periprocedural and up to 27 weeks.)
- Rockwood Clinical Frailty Scale Score(From enrolment, at periprocedural and up to 27 weeks.)
- Cognitron Cognitive Assessment Platform(From enrolment, at periprocedural and up to 27 weeks.)
- PKMAS Gait Analysis Software(From enrolment, at periprocedural and up to 27 weeks.)