This prospective, multicenter, open-label clinical trial is designed to evaluate the safety and efficacy of rapamycin in the treatment of communicating hydrocephalus secondary to intraventricular hemorrhage. Additionally, the underlying pathogenic mechanisms associated with this particular type of hydrocephalus will be investigated in greater depth, and populations that may benefit from rapamycin therapy will be identified.
Communicating hydrocephalus secondary to intraventricular hemorrhage is a serious neurological disorder with the main clinical manifestations of ventricular dilatation, gait disturbance, cognitive dysfunction, and urinary incontinence. At present, the sole treatment option for these patients is cerebrospinal fluid shunting. However, complications resulting from this therapy have necessitated multiple surgeries for some patients, which has a significant impact on their quality of life and financial resources. However, recent studies have identified the PI3K-AKT-mTOR pathway as a key contributor to the sequelae of hemorrhagic hydrocephalus. Furthermore, these studies demonstrated that rapamycin, an inhibitor of the PI3K-AKT-mTOR pathway, inhibited cerebrospinal fluid secretion and ventricular dilation in an animal model of hemorrhagic hydrocephalus sequelae. In light of these findings, we propose a prospective, multicenter, open-label clinical trial to evaluate the efficacy and safety of rapamycin in the treatment of communicating hydrocephalus secondary to intraventricular hemorrhage. The study design was that of a prospective, multicenter, open-label clinical trial. All patients were administered sirolimus (rapamycin) in a dosage of 0.5 mg per capsule. The capsules were provided by the North China Pharmaceutical Company and were stored at room temperature. The treatment course was four weeks, with a dosage of 1.5 mg orally per day. Efficacy and adverse effects were assessed at two weeks, four weeks, the end of treatment, and 12 weeks after the end of treatment, respectively.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
53
All enrolled patients receive treatment with sirolimus (rapamycin)#The prescribed regimen involved a daily oral dosage of 1.5 mg for a duration of four weeks.
Beijing Tiantan Hospital, Capital Medical University
Beijing, Beijing Municipality, China
RECRUITINGThe objective remission rate of rapamycin for 4 weeks in the treatment of communicating hydrocephalus secondary to intraventricular hemorrhage is evaluated using the Idiopathic Normal Pressure Hydrocephalus Grading Scale (IPNHGS).
Disease relief: Improvement of \>1 point on the Idiopathic Normal Pressure Hydrocephalus Grading Scale (iPNHGS) in patients after four weeks of rapamycin treatment compared to pre-treatment. Objective remission rate: The ratio of the number of patients who have achieved disease remission to the total number of patients enrolled in the study.
Time frame: From the commencement of treatment to 4 weeks
Assessment of the incidence and severity of adverse events, serious adverse events, and other safety parameters (e.g., abnormal laboratory results) based on CTCAE V5.0
All events are determined based on CTCAE V5.0
Time frame: From the commencement of treatment to 12 weeks after discontinuation of dosing
The objective remission rate of rapamycin treatment of communicating hydrocephalus secondary to intraventricular hemorrhage is evaluated using the Idiopathic Normal Pressure Hydrocephalus Grading Scale (IPNHGS).
Disease relief: Improvement of \>1 point on the Idiopathic Normal Pressure Hydrocephalus Grading Scale (iPNHGS) in patients after four weeks of rapamycin treatment compared to pre-treatment. Objective remission rate: The ratio of the number of patients who have achieved disease remission to the total number of patients enrolled in the study.
Time frame: From the commencement of treatment to 2 weeks of dosing and 12 weeks after discontinuation of dosing
The objective remission rates of 3 clinical domains is evaluated using the Idiopathic Normal Pressure Hydrocephalus Grading Scale (IPNHGS).
The 3 clinical domains include: gait, urinary incontinence, and cognition. For gait, positive outcome was defined that improvement of \>1 point in the gait section of iNPHGS; for urinary incontinence, a positive outcome was defined that improvement of \>1 point in the urinary section of iNPHGS; For cognition, positive outcome was defined that improvement of \>1 point in the cognition section of iNPHGS
Time frame: From the commencement to 2 weeks of dosing, 4 weeks of dosing and 12 weeks after discontinuation of dosing
Changes in plasma biomarkers
Change in plasma levels of TNF-α, IL-1β, IL-6, IL-10, IL-8 and IL-2R.
Time frame: From the commencement to 2 weeks of dosing, 4 weeks of dosing and 12 weeks after discontinuation of dosing
Change in CSF biomarkers
Change in plasma levels of TNF-α, IL-1β, IL-6, IL-10, IL-8 and IL-2R.
Time frame: From the commencement to 2 weeks of dosing, 4 weeks of dosing and 12 weeks after discontinuation of dosing
Change in Euro-Quality of Life-5 dimension-5L (EQ-5D-5L) descriptive system
Measured using EQ-5D-5L using the descriptive system.
Time frame: From the commencement to 2 weeks of dosing, 4 weeks of dosing and 12 weeks after discontinuation of dosing
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