Post-hemorrhagic Hydrocephalus (PHH)Phase 1/2VENTURE-PHHNCT07662174
Ventricular mTOR Inhibition to Prevent Hydrocephalus After Brain Hemorrhage
A Phase 1/2 study testing Sirolimus (Rapamune®) in people with Post-hemorrhagic Hydrocephalus (PHH), run by Massachusetts General Hospital at 1 site in United States.
Trial summary
Hydrocephalus is a serious condition in which fluid builds up inside the brain, often requiring lifelong surgical placement of a shunt to drain excess cerebrospinal fluid (CSF). One of the most common causes of hydrocephalus is bleeding into the brain's fluid spaces after aneurysm rupture, prematurity, or infection. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Post-hemorrhagic Hydrocephalus (PHH)
- What is being tested?
- Sirolimus (Rapamune®)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2027to 31 Dec 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years
- Diagnosis of aneurysmal subarachnoid hemorrhage (aSAH)
- Hunt Hess grade IV to V
- Radiographic evidence of intraventricular hemorrhage (IVH)
- Clinically indicated EVD placement as part of standard neurocritical care
- Ability to enroll during the acute post-hemorrhagic inflammatory period, ideally within 24 hours of EVD placement
Who cannot join
- Pre-existing ventriculoperitoneal shunt dependence
- Severe baseline immunosuppression
- Uncontrolled systemic infection unrelated to hemorrhage
- Pregnancy
- Anticipated withdrawal of life-sustaining therapy within 24 hours
- Inability to safely receive investigational ventricular therapy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Massachusetts General Hospital Lunder 4 OR for adult surgeries
Boston, Massachusetts, 02114
Carla Fortes, BA, 16175489679, CFORTES@MGH.HARVARD.EDU
Kristopher Kahle, MD, PhD
About this study
Official title: VENTURE-PHH: Ventricular mTOR Inhibition to Prevent Hydrocephalus After Brain Hemorrhage
Hydrocephalus is a serious condition in which fluid builds up inside the brain, often requiring lifelong surgical placement of a shunt to drain excess cerebrospinal fluid (CSF). One of the most common causes of hydrocephalus is bleeding into the brain's fluid spaces after aneurysm rupture, prematurity, or infection. Currently, no medication exists to prevent hydrocephalus from developing after these injuries. The investigators' recent research suggests that hydrocephalus may result not only from blocked fluid pathways but also from harmful inflammation within the brain's ventricular system. The investigators discovered that inflammation activates the choroid plexus, the tissue that produces CSF, causing excessive CSF production and inflammatory injury to the ventricular lining and surrounding brain tissue. The investigators also identified inflammatory biomarkers and extracellular vesicles in human CSF that may enable real-time monitoring of these disease processes.
In this project, the investigators will perform a first-in-human pilot study testing whether targeted "intraventricular mTOR inhibition" can reduce ventricular inflammation and prevent hydrocephalus after severe brain hemorrhage. The medication will be delivered via temporary ventricular drains already in place as part of routine clinical care. The investigators will study safety, inflammation, CSF production, brain imaging changes, and whether patients ultimately require permanent shunts. Although this initial study focuses on adults with hemorrhage-related hydrocephalus, our long-term goal is to develop non-surgical therapies that could help children with hydrocephalus caused by prematurity or infection, especially in regions where access to neurosurgical care and shunt surgery is limited.
Read the detailed description
Hydrocephalus remains one of the most common neurosurgical disorders worldwide and is currently treated primarily with surgical diversion of CSF using implanted shunts. Although lifesaving, shunts frequently fail, require repeated surgeries, and do not directly address the underlying biological injury occurring within the brain and ventricular system. Many patients continue to experience lifelong neurological complications despite surgical treatment. This project has the potential to shift hydrocephalus treatment from surgical management toward mechanism-guided prevention. By targeting ventricular inflammation early after hemorrhage, the investigators aim to prevent the biological processes that drive excessive CSF accumulation, ventricular remodeling, ependymal injury, and chronic inflammatory scarring. Successful completion of this work could establish the first pharmacologic strategy designed to prevent hydrocephalus rather than simply treat its consequences after it develops.
The impact of this approach could extend far beyond adult hemorrhage-related hydrocephalus. Similar inflammatory mechanisms are believed to contribute to hydrocephalus caused by prematurity, infection, and traumatic brain injury. In particular, post-infectious and neonatal hydrocephalus remain major causes of childhood disability and death in many low-resource regions where access to shunt surgery and specialized neurosurgical care is limited. A scalable medical therapy capable of reducing hydrocephalus progression could therefore have a substantial global health impact. In addition, this project establishes a new translational framework for studying the ventricular neuroimmune microenvironment through real-time analyses of CSF biomarkers and extracellular vesicles. These tools may ultimately enable personalized monitoring and targeted treatment approaches for multiple forms of hydrocephalus and related neuroinflammatory disorders.
- Conditions
- Post-hemorrhagic Hydrocephalus (PHH)
- Being tested
- Sirolimus (Rapamune®)
- Keywords
- hydrocephalus, brain hemorrhage, mTOR Inhibition
- Medical subject headings
- Hydrocephalus, Intracranial Hemorrhages
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sirolimus (Rapamune®)Drug
Also called Rapamycin
Ventricular delivery
| Study group | Role | What they receive |
|---|---|---|
| Ventricular mTOR Inhibition to Prevent Hydrocephalus After Brain Hemorrhage | Experimental | The investigators will conduct a prospective, single-center, phase Ib/IIa, biomarker-rich translational pilot study evaluating intraventricular mTOR inhibition in adults with severe aneurysmal subarachnoid hemorrhage (aSAH) who require external ventricular drain (EVD) placement as part of routine neurocritical care management. The central objective of the study is to determine whether early modulation of ventricular immune-secretory signaling is feasible, biologically active, and capable of altering inflammatory CSF physiology and ventricular remodeling following hemorrhage. Receives: Drug: Sirolimus (Rapamune®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
CSF rapamycin concentration
The concentration of rapamycin will be measured in serial CSF samples collected longitudinally through EVDs.
Measured: Baseline, 7 days, and 14 days after rapamycin treatment.
Secondary outcomes (4)
Change in Evans Index
Longitudinal change in the Evans index measured on serial brain MRI to assess ventricular enlargement and progression toward hydrocephalus.
Measured: Baseline, 7 days, and 14 days after rapamycin treatment.
Change in Frontal-Occipital Horn Ratio (FOHR)
Longitudinal change in the frontal-occipital horn ratio measured on serial brain MRI as a marker of ventricular size.
Measured: Baseline, 7 days, and 14 days after rapamycin treatment.
Change in Third Ventricular Width
Longitudinal change in third ventricular width measured on serial brain MRI to evaluate ventricular remodeling.
Measured: Baseline, 7 days, and 14 days after rapamycin treatment.
Change in Ventricular Volume
Change in total ventricular volume quantified by MRI-based volumetric segmentation, when imaging quality permits, to explore treatment effects on ventricular remodeling.
Measured: Baseline, 7 days, and 14 days after rapamycin treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2026
- Study start1 Jan 2027 (estimated)
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Post-hemorrhagic Hydrocephalus (PHH)Studies of the same condition, open and under way.
- More trials run by Massachusetts General 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- The investigators will conduct a prospective, single-center, phase Ib/IIa, biomarker-rich translational pilot study evaluating intraventricular mTOR inhibition in adults with severe aneurysmal subarachnoid hemorrhage (aSAH) who require external ventricular drain (EVD) placement as part of routine neurocritical care management. The investigators anticipate enrollment of approximately 10-15 adults with Hunt-Hess grade IV-V aneurysmal SAH over the 12-month study period.
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kristopher Kahle, Massachusetts General Hospital
- Investigators
- Kristopher Kahle, MD, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07662174
- Sponsor's protocol ID
- 2026P001357
- Acronym
- VENTURE-PHH
- Status last verified
- Jun 2026
- First submitted
- 29 May 2026
- Last updated
- 25 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: The investigators have no plan to share IPD with other researchers.
Publications
Ziai WC, Parry-Jones AR, Thompson CB, Sansing LH, Mullen MT, Murthy SB, Mould A, Nekoovaght-Tak S, Hanley DF. Early Inflammatory Cytokine Expression in Cerebrospinal Fluid of Patients with Spontaneous Intraventricular Hemorrhage. Biomolecules. 2021 Jul 30;11(8):1123. doi: 10.3390/biom11081123.
PubMed 34439789Mahalati K, Kahan BD. Clinical pharmacokinetics of sirolimus. Clin Pharmacokinet. 2001;40(8):573-85. doi: 10.2165/00003088-200140080-00002.
PubMed 11523724Foerster P, Daclin M, Asm S, Faucourt M, Boletta A, Genovesio A, Spassky N. mTORC1 signaling and primary cilia are required for brain ventricle morphogenesis. Development. 2017 Jan 15;144(2):201-210. doi: 10.1242/dev.138271. Epub 2016 Dec 19.
PubMed 27993979Kuo LT, Huang AP. The Pathogenesis of Hydrocephalus Following Aneurysmal Subarachnoid Hemorrhage. Int J Mol Sci. 2021 May 10;22(9):5050. doi: 10.3390/ijms22095050.
PubMed 34068783Holste KG, Xia F, Ye F, Keep RF, Xi G. Mechanisms of neuroinflammation in hydrocephalus after intraventricular hemorrhage: a review. Fluids Barriers CNS. 2022 Apr 1;19(1):28. doi: 10.1186/s12987-022-00324-0.
PubMed 35365172Lolansen SD, Rostgaard N, Barbuskaite D, Capion T, Olsen MH, Norager NH, Vilhardt F, Andreassen SN, Toft-Bertelsen TL, Ye F, Juhler M, Keep RF, MacAulay N. Posthemorrhagic hydrocephalus associates with elevated inflammation and CSF hypersecretion via activation of choroidal transporters. Fluids Barriers CNS. 2022 Aug 10;19(1):62. doi: 10.1186/s12987-022-00360-w.
PubMed 35948938Sadegh C, Xu H, Sutin J, Fatou B, Gupta S, Pragana A, Taylor M, Kalugin PN, Zawadzki ME, Alturkistani O, Shipley FB, Dani N, Fame RM, Wurie Z, Talati P, Schleicher RL, Klein EM, Zhang Y, Holtzman MJ, Moore CI, Lin PY, Patel AB, Warf BC, Kimberly WT, Steen H, Andermann ML, Lehtinen MK. Choroid plexus-targeted NKCC1 overexpression to treat post-hemorrhagic hydrocephalus. Neuron. 2023 May 17;111(10):1591-1608.e4. doi: 10.1016/j.neuron.2023.02.020. Epub 2023 Mar 8.
PubMed 36893755Strahle J, Garton HJ, Maher CO, Muraszko KM, Keep RF, Xi G. Mechanisms of hydrocephalus after neonatal and adult intraventricular hemorrhage. Transl Stroke Res. 2012 Jul;3(Suppl 1):25-38. doi: 10.1007/s12975-012-0182-9.
PubMed 23976902Zhang J, Bhuiyan MIH, Zhang T, Karimy JK, Wu Z, Fiesler VM, Zhang J, Huang H, Hasan MN, Skrzypiec AE, Mucha M, Duran D, Huang W, Pawlak R, Foley LM, Hitchens TK, Minnigh MB, Poloyac SM, Alper SL, Molyneaux BJ, Trevelyan AJ, Kahle KT, Sun D, Deng X. Modulation of brain cation-Cl- cotransport via the SPAK kinase inhibitor ZT-1a. Nat Commun. 2020 Jan 7;11(1):78. doi: 10.1038/s41467-019-13851-6.
PubMed 31911626Mukumbya B, Adeleye AO, Siddig AHE, Mbilinyi RH, Woo J, Agwu C, Min Htike WY, Mustapha MJ, Dada OE, Ramos S, Adereti C, Ssembatya JM, Petitt Z, Still MEH, Blackwood ER, von Isenburg M, Haglund MM, Ukachukwu AK. Outcomes of ventriculoperitoneal shunt surgery for hydrocephalus in children in low- and middle-income countries: a systematic review. J Neurosurg Pediatr. 2025 Aug 15;36(5):570-581. doi: 10.3171/2025.4.PEDS24598. Print 2025 Nov 1.
PubMed 40815859Vinchon M, Rekate H, Kulkarni AV. Pediatric hydrocephalus outcomes: a review. Fluids Barriers CNS. 2012 Aug 27;9(1):18. doi: 10.1186/2045-8118-9-18.
PubMed 22925451Karimy JK, Reeves BC, Damisah E, Duy PQ, Antwi P, David W, Wang K, Schiff SJ, Limbrick DD Jr, Alper SL, Warf BC, Nedergaard M, Simard JM, Kahle KT. Inflammation in acquired hydrocephalus: pathogenic mechanisms and therapeutic targets. Nat Rev Neurol. 2020 May;16(5):285-296. doi: 10.1038/s41582-020-0321-y. Epub 2020 Mar 9.
PubMed 32152460Kahle KT, Klinge PM, Koschnitzky JE, Kulkarni AV, MacAulay N, Robinson S, Schiff SJ, Strahle JM. Paediatric hydrocephalus. Nat Rev Dis Primers. 2024 May 16;10(1):35. doi: 10.1038/s41572-024-00519-9.
PubMed 38755194Karimy JK, Zhang J, Kurland DB, Theriault BC, Duran D, Stokum JA, Furey CG, Zhou X, Mansuri MS, Montejo J, Vera A, DiLuna ML, Delpire E, Alper SL, Gunel M, Gerzanich V, Medzhitov R, Simard JM, Kahle KT. Inflammation-dependent cerebrospinal fluid hypersecretion by the choroid plexus epithelium in posthemorrhagic hydrocephalus. Nat Med. 2017 Aug;23(8):997-1003. doi: 10.1038/nm.4361. Epub 2017 Jul 10.
PubMed 28692063Robert 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 25 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- VENTURE-PHH: Ventricular mTOR Inhibition to Prevent Hydrocephalus After Brain Hemorrhage
- ClinicalTrials.gov ID
- NCT07662174
- Acronym / sponsor ID
- VENTURE-PHH / 2026P001357
- Conditions
- Post-hemorrhagic Hydrocephalus (PHH)
- Keywords
- hydrocephalus, brain hemorrhage, mTOR Inhibition
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 1 Jan 2027 (estimated)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 23 Jun 2026 (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.
Hydrocephalus is a serious condition in which fluid builds up inside the brain, often requiring lifelong surgical placement of a shunt to drain excess cerebrospinal fluid (CSF). One of the most common causes of hydrocephalus is bleeding into the brain's fluid spaces after aneurysm rupture, prematurity, or infection. Currently, no medication exists to prevent hydrocephalus from developing after these injuries. The investigators' recent research suggests that hydrocephalus may result not only from blocked fluid pathways but also from harmful inflammation within the brain's ventricular system. The investigators discovered that inflammation activates the choroid plexus, the tissue that produces CSF, causing excessive CSF production and inflammatory injury to the ventricular lining and surrounding brain tissue. The investigators also identified inflammatory biomarkers and extracellular vesicles in human CSF that may enable real-time monitoring of these disease processes.
In this project, the investigators will perform a first-in-human pilot study testing whether targeted "intraventricular mTOR inhibition" can reduce ventricular inflammation and prevent hydrocephalus after severe brain hemorrhage. The medication will be delivered via temporary ventricular drains already in place as part of routine clinical care. The investigators will study safety, inflammation, CSF production, brain imaging changes, and whether patients ultimately require permanent shunts. Although this initial study focuses on adults with hemorrhage-related hydrocephalus, our long-term goal is to develop non-surgical therapies that could help children with hydrocephalus caused by prematurity or infection, especially in regions where access to neurosurgical care and shunt surgery is limited.
Detailed description
Hydrocephalus remains one of the most common neurosurgical disorders worldwide and is currently treated primarily with surgical diversion of CSF using implanted shunts. Although lifesaving, shunts frequently fail, require repeated surgeries, and do not directly address the underlying biological injury occurring within the brain and ventricular system. Many patients continue to experience lifelong neurological complications despite surgical treatment. This project has the potential to shift hydrocephalus treatment from surgical management toward mechanism-guided prevention. By targeting ventricular inflammation early after hemorrhage, the investigators aim to prevent the biological processes that drive excessive CSF accumulation, ventricular remodeling, ependymal injury, and chronic inflammatory scarring. Successful completion of this work could establish the first pharmacologic strategy designed to prevent hydrocephalus rather than simply treat its consequences after it develops.
The impact of this approach could extend far beyond adult hemorrhage-related hydrocephalus. Similar inflammatory mechanisms are believed to contribute to hydrocephalus caused by prematurity, infection, and traumatic brain injury. In particular, post-infectious and neonatal hydrocephalus remain major causes of childhood disability and death in many low-resource regions where access to shunt surgery and specialized neurosurgical care is limited. A scalable medical therapy capable of reducing hydrocephalus progression could therefore have a substantial global health impact. In addition, this project establishes a new translational framework for studying the ventricular neuroimmune microenvironment through real-time analyses of CSF biomarkers and extracellular vesicles. These tools may ultimately enable personalized monitoring and targeted treatment approaches for multiple forms of hydrocephalus and related neuroinflammatory disorders.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The investigators will conduct a prospective, single-center, phase Ib/IIa, biomarker-rich translational pilot study evaluating intraventricular mTOR inhibition in adults with severe aneurysmal subarachnoid hemorrhage (aSAH) who require external ventricular drain (EVD) placement as part of routine neurocritical care management. The investigators anticipate enrollment of approximately 10-15 adults with Hunt-Hess grade IV-V aneurysmal SAH over the 12-month study period.
| Arm | Type | Receives |
|---|---|---|
| Ventricular mTOR Inhibition to Prevent Hydrocephalus After Brain Hemorrhage | Experimental | Drug: Sirolimus (Rapamune®)The investigators will conduct a prospective, single-center, phase Ib/IIa, biomarker-rich translational pilot study evaluating intraventricular mTOR inhibition in adults with severe aneurysmal subarachnoid hemorrhage (aSAH) who require external ventricular drain (EVD) placement as part of routine neurocritical care management. The central objective of the study is to determine whether early modulation of ventricular immune-secretory signaling is feasible, biologically active, and capable of altering inflammatory CSF physiology and ventricular remodeling following hemorrhage. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age ≥18 years
- Diagnosis of aneurysmal subarachnoid hemorrhage (aSAH)
- Hunt Hess grade IV to V
- Radiographic evidence of intraventricular hemorrhage (IVH)
- Clinically indicated EVD placement as part of standard neurocritical care
Key exclusion criteria (6 listed)
- Pre-existing ventriculoperitoneal shunt dependence
- Severe baseline immunosuppression
- Uncontrolled systemic infection unrelated to hemorrhage
- Pregnancy
- Anticipated withdrawal of life-sustaining therapy within 24 hours
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 |
|---|---|---|
| Sirolimus (Rapamune®)Also: RapamycinVentricular delivery | Drug | Ventricular mTOR Inhibition to Prevent Hydrocephalus After Brain Hemorrhage |
Primary outcome
CSF rapamycin concentration
Time frame: Baseline, 7 days, and 14 days after rapamycin treatment.
The concentration of rapamycin will be measured in serial CSF samples collected longitudinally through EVDs.
4 secondary outcomes
Change in Evans Index
Time frame: Baseline, 7 days, and 14 days after rapamycin treatment.
Change in Frontal-Occipital Horn Ratio (FOHR)
Time frame: Baseline, 7 days, and 14 days after rapamycin treatment.
Change in Third Ventricular Width
Time frame: Baseline, 7 days, and 14 days after rapamycin treatment.
Change in Ventricular Volume
Time frame: Baseline, 7 days, and 14 days after rapamycin treatment.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2026.
- Background: PubMed 34439789Ziai WC, Parry-Jones AR, Thompson CB, Sansing LH, Mullen MT, Murthy SB, Mould A, Nekoovaght-Tak S, Hanley DF. Early Inflammatory Cytokine Expression in Cerebrospinal Fluid of Patients with Spontaneous Intraventricular Hemorrhage. Biomolecules. 2021 Jul 30;11(8):1123. doi: 10.3390/biom11081123.
- Background: PubMed 11523724Mahalati K, Kahan BD. Clinical pharmacokinetics of sirolimus. Clin Pharmacokinet. 2001;40(8):573-85. doi: 10.2165/00003088-200140080-00002.
- Background: PubMed 27993979Foerster P, Daclin M, Asm S, Faucourt M, Boletta A, Genovesio A, Spassky N. mTORC1 signaling and primary cilia are required for brain ventricle morphogenesis. Development. 2017 Jan 15;144(2):201-210. doi: 10.1242/dev.138271. Epub 2016 Dec 19.
- Background: PubMed 34068783Kuo LT, Huang AP. The Pathogenesis of Hydrocephalus Following Aneurysmal Subarachnoid Hemorrhage. Int J Mol Sci. 2021 May 10;22(9):5050. doi: 10.3390/ijms22095050.
- Background: PubMed 35365172Holste KG, Xia F, Ye F, Keep RF, Xi G. Mechanisms of neuroinflammation in hydrocephalus after intraventricular hemorrhage: a review. Fluids Barriers CNS. 2022 Apr 1;19(1):28. doi: 10.1186/s12987-022-00324-0.
- Background: PubMed 35948938Lolansen SD, Rostgaard N, Barbuskaite D, Capion T, Olsen MH, Norager NH, Vilhardt F, Andreassen SN, Toft-Bertelsen TL, Ye F, Juhler M, Keep RF, MacAulay N. Posthemorrhagic hydrocephalus associates with elevated inflammation and CSF hypersecretion via activation of choroidal transporters. Fluids Barriers CNS. 2022 Aug 10;19(1):62. doi: 10.1186/s12987-022-00360-w.
- Background: PubMed 36893755Sadegh C, Xu H, Sutin J, Fatou B, Gupta S, Pragana A, Taylor M, Kalugin PN, Zawadzki ME, Alturkistani O, Shipley FB, Dani N, Fame RM, Wurie Z, Talati P, Schleicher RL, Klein EM, Zhang Y, Holtzman MJ, Moore CI, Lin PY, Patel AB, Warf BC, Kimberly WT, Steen H, Andermann ML, Lehtinen MK. Choroid plexus-targeted NKCC1 overexpression to treat post-hemorrhagic hydrocephalus. Neuron. 2023 May 17;111(10):1591-1608.e4. doi: 10.1016/j.neuron.2023.02.020. Epub 2023 Mar 8.
- Background: PubMed 23976902Strahle J, Garton HJ, Maher CO, Muraszko KM, Keep RF, Xi G. Mechanisms of hydrocephalus after neonatal and adult intraventricular hemorrhage. Transl Stroke Res. 2012 Jul;3(Suppl 1):25-38. doi: 10.1007/s12975-012-0182-9.
- Background: PubMed 31911626Zhang J, Bhuiyan MIH, Zhang T, Karimy JK, Wu Z, Fiesler VM, Zhang J, Huang H, Hasan MN, Skrzypiec AE, Mucha M, Duran D, Huang W, Pawlak R, Foley LM, Hitchens TK, Minnigh MB, Poloyac SM, Alper SL, Molyneaux BJ, Trevelyan AJ, Kahle KT, Sun D, Deng X. Modulation of brain cation-Cl- cotransport via the SPAK kinase inhibitor ZT-1a. Nat Commun. 2020 Jan 7;11(1):78. doi: 10.1038/s41467-019-13851-6.
- Background: PubMed 40815859Mukumbya B, Adeleye AO, Siddig AHE, Mbilinyi RH, Woo J, Agwu C, Min Htike WY, Mustapha MJ, Dada OE, Ramos S, Adereti C, Ssembatya JM, Petitt Z, Still MEH, Blackwood ER, von Isenburg M, Haglund MM, Ukachukwu AK. Outcomes of ventriculoperitoneal shunt surgery for hydrocephalus in children in low- and middle-income countries: a systematic review. J Neurosurg Pediatr. 2025 Aug 15;36(5):570-581. doi: 10.3171/2025.4.PEDS24598. Print 2025 Nov 1.
- Background: PubMed 22925451Vinchon M, Rekate H, Kulkarni AV. Pediatric hydrocephalus outcomes: a review. Fluids Barriers CNS. 2012 Aug 27;9(1):18. doi: 10.1186/2045-8118-9-18.
- Background: PubMed 32152460Karimy JK, Reeves BC, Damisah E, Duy PQ, Antwi P, David W, Wang K, Schiff SJ, Limbrick DD Jr, Alper SL, Warf BC, Nedergaard M, Simard JM, Kahle KT. Inflammation in acquired hydrocephalus: pathogenic mechanisms and therapeutic targets. Nat Rev Neurol. 2020 May;16(5):285-296. doi: 10.1038/s41582-020-0321-y. Epub 2020 Mar 9.
- Individual participant dataSharing planned: No. The investigators have no plan to share IPD with other researchers.
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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.
Kristopher Kahle, MD, PhD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Sirolimus (Rapamune®) in people with Post-hemorrhagic Hydrocephalus (PHH), run by Massachusetts General Hospital at 1 site in United States.
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 6 inclusion and 6 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: opening soon, as of the sponsor's last update on 25 Jun 2026. 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 United States. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kristopher Kahle, M.D., Ph.D. (14143057506, kahle.kristopher@mgh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CSF rapamycin concentration (time frame: Baseline, 7 days, and 14 days after rapamycin treatment.). 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 NCT07662174, which also lists 15 linked publications.
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 25 Jun 2026.