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

NCT ID: NCT06563817

Last Updated: 2024-08-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-31
• Study Completion Date: 2025-07-31

Brief Summary

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.

Detailed Description

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.

Conditions

Communicating Hydrocephalus; Cerebral Intraventricular Hemorrhage; Secondary Normal Pressure Hydrocephalus; Post Hemorrhagic Hydrocephalus

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rapamycin treatment group

All enrolled patients receive treatment with sirolimus (rapamycin), administered in capsule form at a dosage of 0.5 mg per capsule. The capsules, provided by North China Pharmaceutical under the trade name Yixinke, were stored at room temperature. The prescribed regimen involved a daily oral dosage of 1.5 mg for a duration of four weeks.

Sirolimus (rapamycin) bioavailability can be affected by food, based on preliminary results of prior drug use. To maintain consistent blood drug concentrations, sirolimus should be taken with or without food on a constant basis. Grapefruit juice slows CYP3A4-mediated metabolism of sirolimus and potentially enhances P-gp-mediated retrograde transport of sirolimus from the small intestinal epithelium to the intestinal lumen. Therefore, it should not be consumed concurrently with sirolimus.

Group Type: EXPERIMENTAL

Rapamycin

Intervention Type: DRUG

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.

Interventions

Rapamycin

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.

Intervention Type: DRUG

Other Intervention Names

Sirolimus

Eligibility Criteria

Inclusion Criteria

1. Patients with ventricular dilatation due to intraventricular hemorrhage who clinically present with any one or more of new gait disturbances, cognitive deficits, and urinary incontinence after remission of intraventricular hemorrhage symptoms, and whose brain imaging shows an Evans index (EI) of ≥0.3

2. Age ≥ 18 years and ≤ 70 years

3. Signed informed consent form

Exclusion Criteria

1. Participation in another medical trial

2. Have other disease that may affect the patient's symptoms (including gait disturbance, cognitive impairment, urinary incontinence)

3. Allergy to the investigational drug

4. Reduced liver function (increased INR or alanine transaminase concentrations in plasma elevated more than 1.5 times reference values)

5. Reduced kidney function with GFR < 50

6. Concomitant treatment with strong CYP3A4/5 inducers or inhibitors, such as diltiazem, ketoconazole, or rifampicin.

7. Active or uncontrolled chronic infection

8. Women who are pregnant or breastfeeding

9. Patients who are bedridden or require urinary catheters for extended periods of time.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Tiantan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Runfa Tian, MD

Role: STUDY_DIRECTOR

Beijing Tiantan Hospital

Guoyi Gao, MD

Role: STUDY_CHAIR

Beijing Tiantan Hospital

Locations

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Runfa Tian, MD

Role: CONTACT

trftc@126.com

15910996812 ext. +86

Guoyi Gao, MD

Role: CONTACT

gao3@sina.com

13801874393 ext. +86

Facility Contacts

Runfa Tian, MD

Role: primary

trftc@126.com

15910996812 ext. +86

Guoyi Gao, MD

Role: backup

gao3@sina.com

13801874393 ext. +86

References

Robert SM, Reeves BC, Kiziltug E, Duy PQ, Karimy JK, Mansuri MS, Marlier A, Allington G, Greenberg ABW, DeSpenza T Jr, Singh AK, Zeng X, Mekbib KY, Kundishora AJ, Nelson-Williams C, Hao LT, Zhang J, Lam TT, Wilson R, Butler WE, Diluna ML, Feinberg P, Schafer DP, Movahedi K, Tannenbaum A, Koundal S, Chen X, Benveniste H, Limbrick DD Jr, Schiff SJ, Carter BS, Gunel M, Simard JM, Lifton RP, Alper SL, Delpire E, Kahle KT. The choroid plexus links innate immunity to CSF dysregulation in hydrocephalus. Cell. 2023 Feb 16;186(4):764-785.e21. doi: 10.1016/j.cell.2023.01.017.

Reference Type: RESULT

PMID: 36803604 (View on PubMed)

Other Identifiers

HX-A-2024025

Identifier Type: -

Identifier Source: org_study_id