Treatment of brainstem cavernous malformations with sirolimus

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

This study is testing if the drug sirolimus can help people who have had bleeding in the brain due to brainstem cavernous malformations by reducing the chances of more bleeding.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 75 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Huashan Hospital (Academic / other)
• Drugs / interventions: radiation
• Locations: 2 sites (Shanghai, Shanghai Municipality and 1 other locations)
• Trial ID: NCT06091332 on ClinicalTrials.gov

What this trial studies

This pilot trial aims to evaluate the safety and tolerability of sirolimus in patients who have experienced their first symptomatic intracerebral hemorrhage due to brainstem cavernous malformations. Participants will be randomly assigned to receive either sirolimus or a placebo, with the goal of assessing the drug's efficacy in reducing the incidence of rebleeding during high-risk periods. The findings from this trial will help inform the design of a larger definitive clinical trial in the future.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-65 who have had a recent symptomatic intracerebral hemorrhage due to solitary brainstem cavernous malformations.

Not a fit: Patients with a history of cancer, severe bleeding requiring life support, or significant organ dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the risk of rebleeding in patients with brainstem cavernous malformations.

How similar studies have performed: While this approach is novel in the context of treating brainstem cavernous malformations, similar studies using sirolimus for other conditions have shown promising results.

Eligibility criteria

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).

Where this trial is running

Shanghai, Shanghai Municipality and 1 other locations

• Huashan Hospital, Fudan University — Shanghai, Shanghai Municipality, China (Active_not_recruiting)
• Huashan Hospital, Fudan University — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Wei Zhu, Doctor — Huashan Hospital
• Study coordinator: Zongze Li, Doctor

Conditions Cavernous Malformations; Intracerebral Hemorrhage; Brainstem Stroke; Brainstem; Rebleeding rate; Sirolimus