Dimethyl Fumarate Treatment for Intracranial Unruptured Aneurysms.
Study Details
Study Description
Brief Summary
This study was designed to identify whether there is a measurable reduction in inflammation in walls of intracranial aneurysms with oral dimethyl fumarate.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed 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).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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) |
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 Comparator: Placebo placebo with the same appearance (color, taste, size, shape) |
Drug: Placebo
placebo with the same appearance (color, taste, size, shape), 30 patients for this arm.
|
Outcome Measures
Primary Outcome Measures
- Change of aneurysm wall inflammation as measured by HR-VW-MRI. [6 months]
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.
Secondary Outcome Measures
- Change of aneurysmal morphology parameter [6 months]
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.
- Change of inflammatory markers in patients [6 months]
Changes in CRP, TNF-α, IL-1β and IL-6 in patients with unruptured IAs from before treatment to the 6 months follow-up. The CRP, TNF-α, IL-1β and IL-6 levels will be measured at before treatment and at 6 months follow-up.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male or female aged ≥18 years.
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Unruptured IA of ≥3mm identified on imaging (CT, MRI or digital subtraction angiography).
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Aneurysm wall enhancement identified by HR-VWI before treatment.
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Ability to understand the objective of the trial with provision of written informed consent.
Exclusion Criteria:
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MRI contraindications (metallic implant, contrast allergy, claustrophobia, etc).
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Planned treatment of the aneurysm within 12 months.
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Current treatment with drugs that might have an anti-inflammatory effect (aspirin, statins, immunosuppressive drugs, etc.).
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Severely impaired liver or renal function.
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Retreatment of recurrent aneurysm.
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Pregnant or lactating women.
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Malignant diseases (liver disease, kidney disease, congestive heart failure, malignant tumours, etc.).
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Poor compliance.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Neurosurgical Institute & Beijing Tiantan Hospital | Beijing | Beijing | China | 100070 |
Sponsors and Collaborators
- Beijing Tiantan Hospital
- Beijing Neurosurgical Institute
- Beijing Chao Yang Hospital
- Henan Provincial People's Hospital
Investigators
- Study Director: Yisen Zhang, MD, Beijing Neurosurgical Institute & Beijing Tiantan Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BTHDMF