The Safety and Efficacy of Rapamycin on Communicating Hydrocephalus Secondary to Intraventricular Hemorrhage

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.

• 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 [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). [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). [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 [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 [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 [Time frame: From the commencement to 2 weeks of dosing, 4 weeks of dosing and 12 weeks after discontinuation of dosing]