Communicating HydrocephalusPhase 2SaturnNCT06563817
The Safety and Efficacy of Rapamycin on Communicating Hydrocephalus Secondary to Intraventricular Hemorrhage
A Phase 2 study testing Rapamycin in people with Communicating Hydrocephalus and Cerebral Intraventricular Hemorrhage, run by Beijing Tiantan Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Communicating Hydrocephalus, Cerebral Intraventricular Hemorrhage, Secondary Normal Pressure Hydrocephalus
- What is being tested?
- Rapamycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 1 siteChina
- Study dates
- Aug 2024to Jul 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- Active or uncontrolled chronic infection
- Women who are pregnant or breastfeeding
- Patients who are bedridden or require urinary catheters for extended periods of time.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Beijing Tiantan Hospital, Capital Medical University
Beijing, Beijing Municipality, 100070
Runfa Tian, MD, 15910996812 ext. +86, trftc@126.com
Guoyi Gao, MD, 13801874393 ext. +86, gao3@sina.com
About this study
Official title: A Prospective, Multi-center, Open-label Study to Observe the Efficacy and Safety of Rapamycin in the Treatment of Communicating Hydrocephalus Secondary to Intraventricular Hemorrhage
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.
Read the 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
- Being tested
- Rapamycin
- Keywords
- Communicating Hydrocephalus, Cerebral Intraventricular Hemorrhage, Rapamycin, Secondary Normal Pressure Hydrocephalus, Post Hemorrhagic Hydrocephalus
- Medical subject headings
- Hydrocephalus, Cerebral Intraventricular Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RapamycinDrug
Also called Sirolimus
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Rapamycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
All events are determined based on CTCAE V5.0
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From the commencement to 2 weeks of dosing, 4 weeks of dosing and 12 weeks after discontinuation of dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2024
- Study startAug 2024 (estimated)
- Primary completionMay 2025 (estimated)
- Study completionJul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Communicating HydrocephalusStudies of the same condition, open and under way.
- More trials run by Beijing Tiantan HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 53 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Tiantan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Runfa Tian, MD, Study director, Beijing Tiantan HospitalGuoyi Gao, MD, Study chair, Beijing Tiantan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06563817
- Sponsor's protocol ID
- HX-A-2024025
- Acronym
- Saturn
- Status last verified
- Aug 2024
- First submitted
- 9 Aug 2024
- Last updated
- 21 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36803604
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Multi-center, Open-label Study to Observe the Efficacy and Safety of Rapamycin in the Treatment of Communicating Hydrocephalus Secondary to Intraventricular Hemorrhage
- ClinicalTrials.gov ID
- NCT06563817
- Acronym / sponsor ID
- Saturn / HX-A-2024025
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 53 participants (estimated)
- Lead sponsor
- Beijing Tiantan HospitalUniversity, hospital or other
- Study start
- Aug 2024 (estimated)
- Primary completion
- May 2025 (estimated)
- Study completion
- Jul 2025 (estimated)
- First posted
- 21 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Rapamycin treatment group | Experimental | Drug: RapamycinAll 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RapamycinAlso: SirolimusAll 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. | Drug | Rapamycin treatment group |
Primary outcome
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).
Time frame: From the commencement of treatment to 4 weeks
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.
6 secondary outcomes
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2024.
- Results publication: PubMed 36803604Robert 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.
- Individual participant dataSharing planned: No
Related trials for Communicating Hydrocephalus
Active, not recruiting
The ETCHES I Study (Endovascular Treatment of Communicating Hydrocephalus With an Endovascular Shunt)
Hydrocephalus, Communicating, Hydrocephalus
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Runfa Tian, MD study director
Beijing Tiantan Hospital
Guoyi Gao, MD study chair
Beijing Tiantan Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rapamycin in people with Communicating Hydrocephalus and Cerebral Intraventricular Hemorrhage, run by Beijing Tiantan Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Runfa Tian, MD (15910996812 ext. +86, trftc@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). (time frame: From the commencement of treatment to 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06563817, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2024.