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Recruiting NCT06091332

Hemorrhagic Brainstem Cavernous Malformations Treatment With Sirolimus: aSingle Centre, Randomized, Placebo-controlled Pilot Trial

Phase II Interventional Cavernous Malformations Intracerebral Hemorrhage Brainstem Stroke

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Sirolimus, Starch flake.
Who it may be relevant to
Registry conditions: Cavernous Malformations, Intracerebral Hemorrhage, Brainstem Stroke. Basic parameters: 18 years — 65 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
China
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

Hemorrhagic Brainstem Cavernous Malformations Treatment With Sirolimus: a Randomized, Placebo-controlled Pilot Trial

Overview

The aim of this pilot phase trial is to assess the safety and tolerability, and estimate the efficacy of sirolimus in reducing the incidence of ICH during high-risk periods for rebleeding, compared to placebo. This pilot trial will inform the design of a future definitive clinical trial on sirolimus treatment for CCM.

Interventions

  • Drug Sirolimus
    Sirolimus is an mTORC1 inhibitor that has received approval from the U.S. Food and Drug Administration (FDA) and has recently been successfully used to treat lymphatic malformations and venous/lymphatic malformations associated with the same PIK3CA GOF mutations.
  • Drug Starch flake
    The placebo is composed of starch material and is formulated at 0.5 grams per tablet.

Primary outcome measures

  • The primary outcome is to explore the safety of sirolimus in the management of BSCMs. [Time frame: 24 months]
Secondary outcome measures (4)
  • We will measure the tolerability of sirolimus in the management of BSCMs. [Time frame: 24 months]
  • We will measure the occurrence of recurrent ICH from the BSCM within 24 months. [Time frame: 24 months]
  • We will measure the efficacy outcomes in MR [Time frame: 24 months]
  • We will measure several the quality of life [Time frame: 24 months]

Eligibility criteria

Inclusion criteria

  • Age 18-65 years, any gender;
  • Patients who have experienced their first symptomatic BSCM ICH within the six months before randomisation;
  • Diagnosed with solitary BSCM through T2, GRE/T2\*, or SWI MR imaging;
  • ICH within or around the BSCM confirmed by CT /MR;
  • Capable of signing an informed consent form with the accompaniment and understanding of a guardian.

Exclusion criteria

  • Cancer history;
  • Pregnancy or lactation;
  • Sirolimus/starch allergy;
  • Modified Rankin Scale (mRS) score 5, respiratory failure or currently severe bleeding requiring life support treatment;
  • Abnormal liver and/or kidney function (transaminase levels greater than 50, creatinine greater than 110), abnormal white blood cell/platelet counts (white blood cell count below 3.5 or above 9.5 x 109/L or exceeding normal values, platelet count below 100 or above 300);
  • History of previous immunosuppressive therapy;
  • History of prior surgical intervention for CCM ;
  • History of prior cranial radiation therapy ;
  • Familial CCM or people with multiple CCM;
  • Patients with concurrent acute active infections (e.g., severe bacterial, viral, or fungal infections);
  • Uncontrolled diabetes mellitus;
  • Currently participating in another clinical trial;
  • Patient unwilling/unable to undergo MRI.
  • Co-administration of drugs affecting CYP3A4 enzymes (ketoconazole, voriconazole, itraconazole, telithromycin, clarithromycin).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Quadruple blind
Primary purpose
Treatment

Study locations

China · 2 centers
  • Huashan Hospital, Fudan University — Shanghai
  • Huashan Hospital, Fudan University — Shanghai

Publications

  • Ren AA, Snellings DA, Su YS, Hong CC, Castro M, Tang AT, Detter MR, Hobson N, Girard R, Romanos S, Lightle R, Moore T, Shenkar R, Benavides C, Beaman MM, Muller-Fielitz H, Chen M, Mericko P, Yang J, Sung DC, Lawton MT, Ruppert JM, Schwaninger M, Korbelin J, Potente M, Awad IA, Marchuk DA, Kahn ML. PIK3CA and CCM mutations fuel cavernomas through a cancer-like mechanism. Nature. 2021 Jun;594(7862): PMID 33910229
  • Flemming KD, Graff-Radford J, Aakre J, Kantarci K, Lanzino G, Brown RD Jr, Mielke MM, Roberts RO, Kremers W, Knopman DS, Petersen RC, Jack CR Jr. Population-Based Prevalence of Cerebral Cavernous Malformations in Older Adults: Mayo Clinic Study of Aging. JAMA Neurol. 2017 Jul 1;74(7):801-805. doi: 10.1001/jamaneurol.2017.0439. PMID 28492932
  • Ren J, Huang Y, Ren Y, Tu T, Qiu B, Ai D, Bi Z, Bai X, Li F, Li JL, Chen XJ, Feng Z, Guo Z, Lei J, Tian A, Cui Z, Lindner V, Adams RH, Wang Y, Zhao F, Korbelin J, Sun W, Wang Y, Zhang H, Hong T, Ge WP. Somatic variants of MAP3K3 are sufficient to cause cerebral and spinal cord cavernous malformations. Brain. 2023 Sep 1;146(9):3634-3647. doi: 10.1093/brain/awad104. PMID 36995941
  • Yan C, Ye Y, Liu N, Zhang D, Du W, Li Y, Li G, Li C, Li J, Ma S, Dai Z, Xiong Z, Wang Y, Men C, Bi R, Duan Q, Xu W, Husilengtu, Cao Y, Du J, Shi C. Metformin limits cerebral cavernous malformation development by targeting KLF4-mediated mitochondrial damage. Biochem Biophys Res Commun. 2025 Sep 1;777:152241. doi: 10.1016/j.bbrc.2025.152241. Epub 2025 Jun 24. PMID 40570636

Identifiers

NCT: NCT06091332 · 2023-816

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗