Dimethyl Fumarate Treatment for Intracranial Unruptured Aneurysms.

Study Overview
=================
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).

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

Conditions
-----------------
Intracranial Aneurysm, Aneurysm, Brain, Inflammation Vascular

Intervention / Treatment
-----------------
* Drug: Dimethyl fumarate
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female aged ≥18 years. Unruptured IA of ≥3mm identified on imaging (CT, MRI or digital subtraction angiography). Aneurysm wall enhancement identified by HR-VWI before treatment. Ability to understand the objective of the trial with provision of written informed consent. Exclusion Criteria: MRI contraindications (metallic implant, contrast allergy, claustrophobia, etc). Planned treatment of the aneurysm within 12 months. Current treatment with drugs that might have an anti-inflammatory effect (aspirin, statins, immunosuppressive drugs, etc.). Severely impaired liver or renal function. Retreatment of recurrent aneurysm. Pregnant or lactating women. Malignant diseases (liver disease, kidney disease, congestive heart failure, malignant tumours, etc.). Poor compliance.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dimethyl fumarate<br>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<br>* 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.<br>|
| Placebo Comparator: Placebo<br>placebo with the same appearance (color, taste, size, shape) | Drug: Placebo<br>* placebo with the same appearance (color, taste, size, shape), 30 patients for this arm.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Change of inflammatory markers in patients | 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. | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Dimethyl Fumarate, High resolution magnetic resonance