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

NCT06563817 | Recruiting Phase 2 DMC

• 1 other identifier: HX-A-2024025
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• The 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.

  From the commencement of treatment to 4 weeks

Secondary Outcomes (6)

• 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

  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).

  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).

  From the commencement to 2 weeks of dosing, 4 weeks of dosing and 12 weeks after discontinuation of dosing

• Changes in plasma biomarkers

  From the commencement to 2 weeks of dosing, 4 weeks of dosing and 12 weeks after discontinuation of dosing

• Change in CSF biomarkers

  From the commencement to 2 weeks of dosing, 4 weeks of dosing and 12 weeks after discontinuation of dosing

Other Outcomes (1)

• Screening of potential beneficiary population

  From the commencement of treatment to 4 weeks

Study Arms (1)

Rapamycin treatment group

EXPERIMENTAL

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.

Drug: Rapamycin

Interventions

Rapamycin 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.

Also known as: Sirolimus

Rapamycin treatment group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Age ≥ 18 years and ≤ 70 years
• Signed informed consent form

You may not qualify if:

• Participation in another medical trial
• Have other disease that may affect the patient's symptoms (including gait disturbance, cognitive impairment, urinary incontinence)
• Allergy to the investigational drug
• Reduced liver function (increased INR or alanine transaminase concentrations in plasma elevated more than 1.5 times reference values)
• Reduced kidney function with GFR \< 50
• Concomitant treatment with strong CYP3A4/5 inducers or inhibitors, such as diltiazem, ketoconazole, or rifampicin.
• Active or uncontrolled chronic infection
• Women who are pregnant or breastfeeding
• Patients who are bedridden or require urinary catheters for extended periods of time.

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead

Study Sites (1)

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100070, China

RECRUITING

Related Publications (1)

• 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.

  PMID: 36803604 RESULT

MeSH Terms

Conditions

Hydrocephalus; Cerebral Intraventricular Hemorrhage

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Hemorrhage; Intracranial Hemorrhages; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Runfa Tian, MD

  Beijing Tiantan Hospital

  STUDY DIRECTOR

• Guoyi Gao, MD

  Beijing Tiantan Hospital

  STUDY CHAIR

Central Study Contacts

Runfa Tian, MD

CONTACT

15910996812; trftc@126.com

Guoyi Gao, MD

CONTACT

13801874393; gao3@sina.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 9, 2024
• First Posted: August 21, 2024
• Study Start: August 1, 2024
• Primary Completion: May 1, 2025
• Study Completion: July 1, 2025
• Last Updated: August 21, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)