Clincosm LogoSign in Get a demo

CALM: Hemorrhagic Brainstem Cavernous Malformations Treatment With Sirolimus: a Pilot Study

Sponsor
Huashan Hospital (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT06091332
Collaborator
(none)
60
Enrollment
1
Location
3
Arms
25
Anticipated Duration (Months)
2.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study employs a single-center, prospective, randomized controlled, double-blind exploratory research design. To investigate whether Sirolimus can reduce the rebleeding rate of brainstem cavernous malformations within 24 months after the first symptomatic bleeding event.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
60 participants
Allocation:
Randomized
Intervention Model:
Single Group Assignment
Intervention Model Description:
We will recruit subjects from the Neurosurgery Outpatient Department of Huashan Hospital, affiliated with Fudan University.We will recruit subjects from the Neurosurgery Outpatient Department of Huashan Hospital, affiliated with Fudan University.
Masking:
Triple (Participant, Care Provider, Investigator)
Masking Description:
A double-blind design means that throughout the entire study, neither the participating patients nor the investigators are aware of which treatment group the patients are assigned to, in order to minimize potential biases. The blinding level is double-blind, which means that both the patients in the treatment group and those in the control group, as well as the investigators, are unaware of the treatment the patients receive, ensuring objectivity and reliability of the study results.
Primary Purpose:
Treatment
Official Title:
Hemorrhagic Brainstem Cavernous Malformations Treatment With Sirolimus: a Pilot Study
Anticipated Study Start Date :
Dec 1, 2023
Anticipated Primary Completion Date :
Dec 31, 2025
Anticipated Study Completion Date :
Dec 31, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: High-dose sirolimus group

Participants will receive oral sirolimus with a target blood concentration of 10-15ng/ml continuously for 12 months.

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.
Other Names:
  • Rapamune

    		•
    Experimental: Low-dose sirolimus group

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

    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.
    Other Names:
  • Rapamune

    		•
    Placebo Comparator: Placebo control group

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

    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.
    Other Names:
  • Rapamune

    		•

    Outcome Measures

    Primary Outcome Measures

    1. To investigate whether Sirolimus can reduce the rebleeding rate of brainstem cavernous malformations within 24 months after the first symptomatic bleeding event. [24 months]

      Through a randomized controlled exploratory study, we aim to assess whether Sirolimus can reduce the risk of rebleeding by 50% within one year after the first symptomatic bleeding event in patients with brainstem cavernous malformations.

    Secondary Outcome Measures

    1. To explore the effectiveness assessment of Sirolimus in reducing the occurrence of subclinical bleeding in brainstem cavernous malformations. [24 months]

      Brainstem cavernous malformations may manifest as subclinical microbleeds, undetectable by CT scan with no new hemorrhage seen. We will analyze the quantitative susceptibility mapping (QSM) sequence of brainstem cavernous malformations through head MRI to assess whether there is imaging evidence of micro-bleeding.

    2. To explore the treatment dose of Sirolimus and evaluate its side effects in the management of brainstem cavernous malformations. [24 months]

      By dividing the patients into high-dose Sirolimus and low-dose Sirolimus groups, we will assess the therapeutic effects of different doses of Sirolimus in the treatment of brainstem cavernous malformations following bleeding events. This study aims to identify an appropriate treatment dose and evaluate the occurrence of side effects, as well as the safety of Sirolimus in treatment.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Age between 18 and 65 years, any gender.

    2. Patients who experienced their first symptomatic bleeding caused by brainstem cavernous malformation within six months.

    3. Diagnosed with brainstem cavernous malformation through SWI and MR T2 imaging.

    4. Confirmed intracranial or perilesional bleeding by CT scan.

    5. Capable of signing an informed consent form with the understanding and accompaniment of a guardian.

    Exclusion Criteria:

    1. History of cancer.

    2. Pregnancy or lactation.

    3. Hypersensitivity to rapamycin or placebo.

    4. Respiratory failure or severe bleeding requiring life support treatment.

    5. Abnormal liver or kidney function (transaminases greater than 50, creatinine greater than 110), white blood cell/platelet abnormalities (white blood cell count below 3.5 or above 9.5 x 10^9/L, platelet count below 100 or above 300).

    6. History of previous immunosuppressive therapy.

    7. History of bleeding more than 6 months ago.

    8. History of surgical treatment for cavernous malformation.

    9. History of radiation therapy for cerebral cavernous malformation.

    10. History of previous statin medication treatment.

    11. History of previous propranolol treatment.

    12. Presence of intracranial cavernous malformation in a location other than the brainstem.

    13. Patients with concurrent acute active infections (such as severe bacterial, viral, or fungal infections).

    14. Uncontrolled diabetes.

    15. Participation in other clinical trials.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Huashan Hospital, Fudan University Shanghai Shanghai China 200040

    Sponsors and Collaborators

    • Huashan Hospital

    Investigators

    • Principal Investigator: Wei Zhu, Doctor, Huashan Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Wei Zhu, Huashan Hospital, Fudan University, Huashan Hospital
    ClinicalTrials.gov Identifier:
    NCT06091332
    Other Study ID Numbers:
    • 2023-816
    First Posted:
    Oct 19, 2023
    Last Update Posted:
    Oct 19, 2023
    Last Verified:
    Oct 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Wei Zhu, Huashan Hospital, Fudan University, Huashan Hospital
    Cavernous Malformations
    Brainstem
    Rebleeding rate
    Sirolimus
    Additional relevant MeSH terms:
    Congenital Abnormalities
    Sirolimus

    Study Results

    No Results Posted as of Oct 19, 2023