Dimethyl Fumarate Treatment for Intracranial Unruptured Aneurysms.

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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Intracranial Aneurysm; Aneurysm, Brain; Inflammation Vascular
• Intervention / Treatment: Drug: Dimethyl fumarate; Drug: Placebo

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 Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yisen Zhang, MD; Phone Number: +86-15001232615; Email: zhang-yisen@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100070
      • Beijing Neurosurgical Institute & Beijing Tiantan Hospital
      • Contact: Yisen Zhang, MD; Phone Number: +86-15001232615; Email: zhang-yisen@163.com
      • Contact: Jiliang Huang; Phone Number: +86-18829793414; Email: linkgo@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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.

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

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Collaborators: Beijing Chao Yang Hospital; Henan Provincial People's Hospital; Beijing Neurosurgical Institute
• Investigators: Study Director: Yisen Zhang, MD, Beijing Neurosurgical Institute & Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 31, 2023
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: July 16, 2023
• First Submitted That Met QC Criteria: July 16, 2023
• First Posted (Actual): July 25, 2023

Study Record Updates

• Last Update Posted (Actual): July 25, 2023
• Last Update Submitted That Met QC Criteria: July 16, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Dimethyl Fumarate; High resolution magnetic resonance
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Arterial Diseases; Inflammation; Aneurysm; Intracranial Aneurysm; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Dimethyl Fumarate
• Other Study ID Numbers: BTHDMF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data are available on reasonable request.
• IPD Sharing Time Frame: starting 6 months after publication
• IPD Sharing Access Criteria: Data are available on reasonable request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes