Aneurysm, Brain, Inflammation Vascular, Intracranial Aneurysm
Conditions
Keywords
Dimethyl Fumarate, High resolution magnetic resonance
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.
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).
Interventions
DRUGDimethyl 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.
DRUGPlacebo
placebo with the same appearance (color, taste, size, shape), 30 patients for this arm.
Sponsors
Beijing Tiantan Hospital
Beijing Neurosurgical Institute
Beijing Chao Yang Hospital
Henan Provincial People's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The patients with intracranial aneurysms will be numbered and randomly divided into two groups, 30 patients in each group, and seal them. Through blind method, one group will be given 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). The other group took placebo with the same appearance (color, taste, size, shape) as the test drug.
Intervention model description
A total of 60 patients will be enrolled in this study. Randomly divide the patients into experimental group and placebo group according to 1:1 ratio.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 6 months. 3. Current treatment with drugs that might have an anti-inflammatory effect (aspirin, statins, immunosuppressive drugs, angiotensin converting enzyme, 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 with treatment or follow--up (patients who refuse to take medication as prescribed, patients who decline imaging follow--up or blood test, etc).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of aneurysm wall inflammation as measured by HR-VW-MRI. | 6 months | At the end of 6 months, the changes of Wall enhancement index (WEI) and wall enhancement volume rate (WEVR) on HR-VW-MRI will be quantitatively compared between the DMF group and placebo group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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-Iβ, IL-2R, IL-6, IL-8 and IL-10 in patients with unruptured IAs from before treatment to the 6 months follow-up. The inflammatory markers levels will be measured at before treatment and at 6 months follow-up. |
Countries
China
Contacts
STUDY_DIRECTORYisen Zhang, MD
Beijing Neurosurgical Institute & Beijing Tiantan Hospital
Outcome results
None listed