RecruitingPhase 2NCT06091332

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

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


Sponsor

Huashan Hospital

Enrollment

75 participants

Start Date

Jan 5, 2024

Study Type

INTERVENTIONAL

Conditions

Summary

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.


Eligibility

Min Age: 18 YearsMax Age: 65 Years

Inclusion Criteria5

  • 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 Criteria14

  • 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).

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Interventions

DRUGSirolimus

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.

DRUGStarch flake

The placebo is composed of starch material and is formulated at 0.5 grams per tablet.


Locations(2)

Huashan Hospital, Fudan University

Shanghai, Shanghai Municipality, China

Huashan Hospital, Fudan University

Shanghai, Shanghai Municipality, China

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NCT06091332


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