Dimethyl Fumarate Treatment for Intracranial Unruptured Aneurysms.

Intracranial Aneurysm Clinical Trial

Official title:

Dimethyl Fumarate Treatment for Intracranial Unruptured Aneurysms: a Double Blind Randomized Controlled Trail

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05959759
• Other study ID #: BTHDMF
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: July 31, 2023
• Est. completion date: June 1, 2024

Study information

• Verified date: July 2023
• Source: Beijing Tiantan Hospital
• Contact: Yisen Zhang, MD
• Phone: +86-15001232615
• Email: zhang-yisen[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study was designed to identify whether there is a measurable reduction in inflammation in walls of intracranial aneurysms with oral dimethyl fumarate.

Description:

Intracranial aneurysm (IA) is a common cerebrovascular disease and the main cause of nontraumatic subarachnoid hemorrhage. Once ruptured, it will cause a high mortality rate, and nearly half of the survivors will also have disabilities. After comparing surgical risk and rupture risk, a significant proportion of patients with intracranial aneurysms choose conservative observation.

Previous studies suggest that inflammation of aneurysmal wall is a high-risk factor of rupture. Dimethyl fumarate (DMF) acts as an anti-inflammatory agent by activating nuclear factor erythroid 2-related factor 2(Nrf2) and other pathways. Animal experiments found dimethyl fumarate reduces the formation and rupture of intracranial aneurysms.

MRI High-resolution vessel wall imaging (HR-VWI) has become a valuable method to assess the Wall of unruptured intracranial aneurysms. Using HR-VWI, it may be possible to detect smaller or more subtle areas of signal enhancement and change, which may give a more precise understanding of the pathology.

In this study, DMF was evaluated for its ability to reduce inflammation of the aneurysm wall measured with High-resolution Vessel Wall Imaging (HR-VWI).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: June 1, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or female aged =18 years.

2. Unruptured IA of =3mm identified on imaging (CT, MRI or digital subtraction angiography).

3. Aneurysm wall enhancement identified by HR-VWI before treatment.

4. Ability to understand the objective of the trial with provision of written informed consent.

Exclusion Criteria:

1. MRI contraindications (metallic implant, contrast allergy, claustrophobia, etc).

2. Planned treatment of the aneurysm within 12 months.

3. Current treatment with drugs that might have an anti-inflammatory effect (aspirin, statins, immunosuppressive drugs, etc.).

4. Severely impaired liver or renal function.

5. Retreatment of recurrent aneurysm.

6. Pregnant or lactating women.

7. Malignant diseases (liver disease, kidney disease, congestive heart failure, malignant tumours, etc.).

8. Poor compliance.

Related Conditions & MeSH terms

• Aneurysm
• Aneurysm, Brain
• Inflammation
• Inflammation Vascular
• Intracranial Aneurysm

Intervention

Drug:
• Dimethyl fumarate
dimethyl fumarate enteric capsule (the initial dose is 120 mg twice a day, and after 7 days, the dose will be increased to the maintenance dose of 240 mg twice a day, for 6 months), 30 patients for this arm.
• Placebo
placebo with the same appearance (color, taste, size, shape), 30 patients for this arm.

Locations

Country	Name	City	State
China	Beijing Neurosurgical Institute & Beijing Tiantan Hospital	Beijing	Beijing

Sponsors (4)

Lead Sponsor	Collaborator
Beijing Tiantan Hospital	Beijing Chao Yang Hospital, Beijing Neurosurgical Institute, Henan Provincial People's Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of aneurysm wall inflammation as measured by HR-VW-MRI.	Change of aneurysm wall enhancement index of at least 20% on HR-VM-MRI at the end of 6 months of dimethyl fumarate treatment, compared to no treatment.	6 months
Secondary	Change of aneurysmal morphology parameter	The proportion of morphological growth of aneurysms from before treatment to the 6 months follow-up. An increase = 1mm in any diameter or the appearance of a daughter sac will be defined as growth in aneurysmal morphology.	6 months
Secondary	Change of inflammatory markers in patients	Changes in CRP, TNF-a, IL-1ß and IL-6 in patients with unruptured IAs from before treatment to the 6 months follow-up. The CRP, TNF-a, IL-1ß and IL-6 levels will be measured at before treatment and at 6 months follow-up.	6 months