Acetazolamide for Treating NPH in Shunt-candidates Patients: an Open Label Feasibility Trial
试验速览
- 阶段
- 2 期
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Change from Baseline Gait
研究概览
简要总结
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.
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
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •Are 50 years old or older.
- •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.
- •Patients who underwent large-volume spinal tap and subsequently improved clinically by at least 10% in gait function or cognition.
排除标准
- •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.
研究组 & 干预措施
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).
干预措施: Acetazolamide (Drug)
结局指标
主要结局
Change from Baseline Gait
时间窗: 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).
Change from Baseline Balance
时间窗: 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).
次要结局
- Change from Baseline verbal fluency(Baseline, week 4)
- Change from Baseline concentration function(Baseline, week 4)
- Change from Baseline visuospatial function(Baseline, week 4)