Acetazolamide for Treating NPH in Shunt-candidates Patients

只有注册用户可以翻译文章

登陆注册

链接已保存到剪贴板

状态招聘中

赞助商

Rabin Medical Center

临床试验: NCT03779594

BioSeek: nct03779594

关键词

抽象

Normal pressure hydrocephalus (NPH) consists of a triad of gait disturbance, cognitive deterioration, and urinary incontinence and is characterized by enlarged cerebral ventricles. Current treatment recommendations are based on surgical diversion of Cerebrospinal fluid (CSF), by a ventriculoperitoneal shunt. When patients are appropriately selected, shunting for NPH has a sustained effect in one-half to two-thirds of patients with a reasonable complication rate. However, evidence regarding the efficacy of shunt surgery consists largely of observational studies with relatively short-term follow-up.

With regards to the adverse effects of shunting, even though decreased substantially in recent years, shunt complications are still common. Recent studies report ten to twenty-two percent of serious adverse effects following shunt surgery, mainly subdural hematoma (SDH) requiring surgery, infection, and cerebral infarction or hemorrhage. Most complication occur in the first year after the procedure. Many others suffer from adverse events that considered non-serious, such as postural headache and asymptomatic SDH.

Since shunt complications are common and potentially severe, there is a need for a better way to identify those patients that will likely benefit from shunting, and find alternative treatments for those unwilling or unable to withstand surgery.

Acetazolamide has been shown to reduce the production of CSF in clinical cases of raised intracranial pressure. It is considered the drug of choice for the treatment of idiopathic intracranial hypertension (pseudotumor cerebri). Intuitively, acetazolamide can be effective for the treatment of NPH by reducing the volume of CSF in the brain, and serve as a medical alternative to shunting. Few case reports and small series demonstrated improvement in MRI abnormalities in NPH-patients after administrating the medication.

This open-label study will examine the feasibility and effectiveness of acetazolamide in NPH-diagnosed patients who are shunt-candidates. Patients will be treated from time of diagnosis, and gait and cognition will be evaluated after 2-6 weeks. This trial would possibly pave the way to a larger randomized placebo-controlled trials, and perhaps offer a medical alternative to surgery for elderly patients and for patients for which operation is contraindicated.

日期

最后验证:	11/30/2018
首次提交:	12/09/2018
提交的预估入学人数:	12/16/2018
首次发布:	12/18/2018
上次提交的更新:	12/16/2018
最近更新发布:	12/18/2018
实际学习开始日期:	11/30/2018
预计主要完成日期:	11/30/2019
预计完成日期:	11/30/2019

状况或疾病

Normal Pressure Hydrocephalus

干预/治疗

Drug: treatment group

相

相 2

手臂组

臂	干预/治疗
Experimental: treatment group patients who met the inclusion criteria will be allocated to the treatment group, and will receive acetazolamide from time of diagnosis until shunt surgery (2-6 weeks).	Drug: treatment group Patients will be assign and treated by acetazolamide from time of allocation until surgery (2-6 weeks after treatment initiation). The maximal dose of acetazolamide will be the same dose used to treat glaucoma, considering similarity of patients' characteristics, such as age and polypharmacy. We will start at a low dose of 250 mg once a day, and increase it slowly to a maximal dose of 500 mg twice a day. Dose will be individualized according to side-effects and tolerability. Renal and liver function tests will be performed before initiation of treatment, and will be examined again two weeks after treatment had begun.

臂

干预/治疗

Experimental: treatment group

patients who met the inclusion criteria will be allocated to the treatment group, and will receive acetazolamide from time of diagnosis until shunt surgery (2-6 weeks).

Drug: treatment group

Patients will be assign and treated by acetazolamide from time of allocation until surgery (2-6 weeks after treatment initiation). The maximal dose of acetazolamide will be the same dose used to treat glaucoma, considering similarity of patients' characteristics, such as age and polypharmacy. We will start at a low dose of 250 mg once a day, and increase it slowly to a maximal dose of 500 mg twice a day. Dose will be individualized according to side-effects and tolerability. Renal and liver function tests will be performed before initiation of treatment, and will be examined again two weeks after treatment had begun.

资格标准

有资格学习的年龄	50 Years 至 50 Years
有资格学习的性别	All
接受健康志愿者	是
标准	Inclusion Criteria: Included will be subjects with a probable diagnosis of NPH. The diagnosis will be based primarily on presence of gait impairment plus at least one other impairment in urinary symptoms, cognition impairment or both. 1. Are 50 years old or older. 2. Patients who meet the criteria for NPH based on: - A typical personal history. - A typical brain imaging on head CT or MRI. - Normal lumbar puncture findings excluding other conditions. - Exclusion of other more likely diagnosis. 3. Patients who underwent large-volume spinal tap and subsequently improved clinically by at least 10% in gait function or cognition. Exclusion Criteria: - Cirrhosis or marked liver disease or dysfunction. - Severe renal disease or dysfunction. - Acidosis. - Hypersensitivity to acetazolamide, sulfonamides, or any component of the formulation. - Decreased sodium and/or potassium levels. - Adrenocortical insufficiency. - Patients with cognitive impairment who will not be able to give informed consent.

结果

主要结果指标

1. Change from Baseline Gait [Baseline, week 4]

Change from Baseline gait will be evaluated by the neurosurgery department's physiotherapist, using the timed-up-and-go (TUG) test (measured in seconds, higher values represent a worse outcome). Patients will be evaluated at baseline (before treatment is started) and again before surgery (4 weeks later).

2. Change from Baseline Balance [Baseline, week 4]

Change from Baseline balance will be evaluated by the neurosurgery department's physiotherapist, using the TINETTI balance assessment score. (0-28 scale, higher values represent a better outcome). Patients will be evaluated at baseline (before treatment is started) and again before surgery (4 weeks later).

次要成果指标

1. Change from Baseline concentration function [Baseline, week 4]

concentration function will be evaluated by the neurosurgery department's neuropsychologist using the color trial test (seconds, higher values represent a worse outcome). Patients will be evaluated at baseline (before treatment is started) and again before surgery (4 weeks later).

2. Change from Baseline visuospatial function [Baseline, week 4]

visuospatial function will be evaluated by the neurosurgery department's neuropsychologist using the clock drawing test (0-10 scale, higher values represent a better outcome). Patients will be evaluated at baseline (before treatment is started) and again before surgery (4 weeks later).

3. Change from Baseline verbal fluency [Baseline, week 4]

verbal fluency will be evaluated by the neurosurgery department's neuropsychologist using the verbal fluency test (Controlled Oral Word Association Test, number of words in one minute, higher values represent a better outcome). Patients will be evaluated at baseline (before treatment is started) and again before surgery (4 weeks later).

其他成果措施

1. adverse effects [week 2-6]

All adverse effects that may be attributed to the treatment will be recorded

Acetazolamide for Treating NPH in Shunt-candidates Patients

关键词

headache

hematoma

hemorrhage

infarction

atrophy

cerebral infarction

hydrocephalus

pseudotumor cerebri

urinary incontinence

抽象

日期

状况或疾病

干预/治疗

相

手臂组

资格标准

结果

科学支持的最完整的草药数据库