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

Fudan University

Status and phase: Enrolling; Phase 2

Conditions: Brainstem Stroke; Cavernous Malformations; Intracerebral Hemorrhage

Treatments: Drug: Starch flake; Drug: Sirolimus

Study type: Interventional

Funder types: Other

Identifiers

NCT06091332

2023-816

Details and patient eligibility

About

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.

Enrollment: 75 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

1. Cancer history;
2. Pregnancy or lactation;
3. Sirolimus/starch allergy;
4. Modified Rankin Scale (mRS) score 5, respiratory failure or currently severe bleeding requiring life support treatment;
5. 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);
6. History of previous immunosuppressive therapy;
7. History of prior surgical intervention for CCM ;
8. History of prior cranial radiation therapy ;
9. Familial CCM or people with multiple CCM;
10. Patients with concurrent acute active infections (e.g., severe bacterial, viral, or fungal infections);
11. Uncontrolled diabetes mellitus;
12. Currently participating in another clinical trial;
13. Patient unwilling/unable to undergo MRI.
14. Co-administration of drugs affecting CYP3A4 enzymes (ketoconazole, voriconazole, itraconazole, telithromycin, clarithromycin).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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75 participants in 3 patient groups, including a placebo group

High-dose sirolimus group

Experimental group

Description:

Participants will receive oral sirolimus with a target blood concentration of 9-15ng/ml continuously for 12 months.

Treatment:

Drug: Sirolimus

Low-dose sirolimus group

Experimental group

Description:

Participants will receive oral sirolimus with a target blood concentration of 3-7ng/ml continuously for 12 months

Treatment:

Drug: Sirolimus

Placebo control group

Placebo Comparator group

Description:

Participants will receive oral placebo(starch formulation) for 12 months.

Treatment:

Drug: Starch flake