Family-Based Moyamoya Susceptibility and Early Detection (FAMES)

The FAME Study: A Family-Based Cohort Study on Moyamoya Disease Susceptibility and Early Screening

This single-center, prospective, family-based observational cohort study aims to investigate susceptibility to moyamoya disease (MMD) and to develop strategies for early screening in individuals at increased familial risk. The study will enroll three groups: patients with MMD, their first-degree relatives, and healthy controls without a family history of MMD.

The rationale for this study is that MMD has an important genetic component, but genetic susceptibility alone does not fully explain disease onset. Current diagnosis often relies on angiographic evaluation after symptoms have already appeared. This study seeks to identify earlier, less invasive biological and imaging markers that may help detect individuals at high risk before overt clinical disease develops.

At baseline, participants will undergo collection of demographic and clinical data, vascular risk factors, neurological assessments, routine laboratory testing, and 5T high-resolution magnetic resonance imaging. Biospecimens including blood, urine, stool, saliva, and nasal swabs will be collected for multi-omics and biomarker analyses; surgically obtained tissue specimens may also be collected from patients undergoing clinically indicated surgery.

Participants in the patient and first-degree relative groups will be followed annually for 3 years, primarily by telephone or online questionnaire, with optional repeat 5T MRI during follow-up. The primary objective is to identify baseline biological and imaging features associated with incident MMD in first-degree relatives and to establish an interpretable early-screening framework for high-risk populations.

Study Overview

• Status: Recruiting
• Conditions: Moyamoya Disease
• Intervention / Treatment: Diagnostic test: 5T High-Resolution MRI

Detailed Description

Moyamoya disease (MMD) is a chronic, progressive cerebrovascular disorder characterized by progressive stenosis or occlusion of the terminal internal carotid arteries and their major branches, accompanied by the development of abnormal collateral vessels. Although genetic susceptibility plays an important role in MMD, incomplete penetrance suggests that non-genetic factors, including immune, inflammatory, metabolic, microbial, and environmental influences, may also contribute to disease onset and progression. Earlier identification of high-risk individuals remains challenging because definitive diagnosis is often made only after clinical symptoms appear.

This study is an investigator-initiated, single-center, prospective, non-randomized, non-interventional observational cohort study conducted at Beijing Hospital. A total of 700 participants are planned for enrollment, including 400 patients with MMD, 200 first-degree relatives of patients with MMD, and 100 healthy controls without a family history of MMD. The overall study duration is 5 years, and the expected participation time for each participant is approximately 3 years.

The main objective is to identify early biological and imaging markers of MMD and to evaluate susceptibility in individuals with familial risk. By comparing patients, unaffected first-degree relatives, and healthy controls at baseline, and by prospectively following the relative group, the study aims to determine which baseline features are associated with future disease development and to define risk factors that may support early screening strategies. The study also seeks to generate a multimodal panel of candidate markers and to build an interpretable early warning framework for high-risk populations.

At baseline, the study will collect demographic data, family history, medical history, medication use, vascular risk factors, smoking and alcohol exposure, neurological status, physiological measures, and lifestyle information. All groups will undergo routine laboratory testing and 5T high-resolution MRI at enrollment. Biospecimens will include blood, urine, stool, saliva, and nasal swabs for analyses such as inflammatory markers, metabolomics, and microbiome profiling. For patients who undergo clinically indicated surgery, operative tissue specimens may also be collected without adding surgical risk.

Follow-up will be performed once yearly for 3 years, mainly by telephone or online questionnaire, in the patient and first-degree relative groups. Participants who are willing may return for optional repeat 5T MRI. Follow-up assessments will include new diagnosis of MMD or suspected cerebrovascular events in the relative group, disease progression in the patient group, functional outcome by modified Rankin Scale, changes in symptoms and daily activity, medication changes, and control of major risk factors. If new MMD or stroke-related events are suspected, relevant medical records and imaging data will be collected for outcome adjudication.

The primary outcomes are: (1) incident MMD during follow-up in first-degree relatives, confirmed by clinical diagnosis and imaging findings; and (2) disease progression and prognosis in patients with MMD, including recurrent stroke or transient ischemic attack, rehospitalization, repeat surgery or intervention, and functional outcome. Secondary outcomes include imaging progression, cardiovascular or cerebrovascular death and all-cause mortality, and post-stroke disability defined as modified Rankin Scale score greater than 3.

The analytical strategy will include baseline cross-sectional comparisons across the three groups and longitudinal analysis of first-degree relatives according to whether MMD develops during follow-up. Candidate biomarkers and imaging features associated with future disease onset will be evaluated and integrated into prediction models using regression-based and/or machine-learning approaches, with assessment of discrimination, calibration, and potential clinical utility for early screening.

• Study Type: Observational
• Enrollment (Estimated): 700

Contacts and Locations

• Study Contact: Name: Dong Zhang, MD; Phone Number: +86-13801121292; Email: zhangdong0660@aliyun.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100730
      • Recruiting
      • Beijing Hospital
      • Contact: Dong Zhang, MD; Phone Number: +86-13801121292; Email: zhangdong0660@aliyun.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

This is a single-center, family-based prospective observational cohort study conducted at Beijing Hospital. The study plans to enroll 700 participants, including 400 patients with moyamoya disease, 200 first-degree relatives of patients with moyamoya disease, and 100 healthy controls without a family history of moyamoya disease. The study population is designed to compare patients, unaffected first-degree relatives at familial risk, and healthy controls in order to identify early biological and imaging markers, evaluate disease susceptibility, and develop early screening strategies for high-risk populations.

Description

Inclusion Criteria:

• Participants must belong to 1 of the following 3 cohorts:

Moyamoya disease cohort: diagnosed with primary moyamoya disease according to standard diagnostic criteria, with progressive stenosis or occlusion at the terminal internal carotid arteries and/or their major branches and typical collateral vessels on DSA, CTA, or MRA; newly diagnosed and previously diagnosed cases are both eligible; no age or sex restriction.

First-degree relative cohort: first-degree blood relatives of patients with moyamoya disease, including parents, children, and siblings; no age or sex restriction; no clinical diagnosis of moyamoya disease and no history of stroke or other cerebrovascular events at enrollment; baseline MRI does not show definite moyamoya disease, although mild changes are allowed.

Healthy control cohort: no family history of moyamoya disease; no personal history of cerebrovascular disease; no major abnormalities on physical examination or baseline screening; age and sex distribution matched as closely as possible to the moyamoya disease cohort.

Exclusion Criteria:

• Major systemic or central nervous system diseases that may interfere with study results or substantially affect survival or adherence, such as advanced malignant tumors, active tuberculosis or other serious infections, active systemic lupus erythematosus, or severe hepatic or renal dysfunction.

Atypical cerebrovascular lesions on baseline imaging, such as widespread atherosclerotic stenosis or congenital vascular malformations.

Inability to complete examinations or follow-up, including MRI contraindications such as non-compatible metal implants or severe claustrophobia, expected difficulty completing follow-up because of long-term relocation, poor communication access, poor adherence, or other situations judged by the investigators to make participation inappropriate.

Pregnant women.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Moyamoya Disease Patients; Participants with moyamoya disease diagnosed according to standard imaging criteria, including newly diagnosed or previously diagnosed cases. Typical findings may be identified on DSA, CTA, or MRA. This observational cohort will undergo baseline clinical assessment, routine laboratory testing, 5T high-resolution MRI, and biospecimen collection. Planned enrollment: 400.	Diagnostic test: 5T High-Resolution MRI; 5T high-resolution MRI will be performed in all cohorts at baseline enrollment. During follow-up, repeat 5T MRI may be performed optionally in participants who are willing to return for imaging reassessment.
First-Degree Relatives of Patients With Moyamoya Disease; First-degree blood relatives of patients with moyamoya disease, including parents, children, and siblings, without a clinical diagnosis of moyamoya disease or prior cerebrovascular events at enrollment. Baseline MRI must not show definite moyamoya disease, although mild changes may be allowed. Participants will undergo baseline assessment and annual follow-up for 3 years to identify incident moyamoya disease and early risk markers. Planned enrollment: 200.	Diagnostic test: 5T High-Resolution MRI; 5T high-resolution MRI will be performed in all cohorts at baseline enrollment. During follow-up, repeat 5T MRI may be performed optionally in participants who are willing to return for imaging reassessment.
Healthy Controls; Healthy participants without a family history of moyamoya disease and without a personal history of cerebrovascular disease. Participants should have no major abnormalities on baseline screening, and age and sex distribution will be matched as closely as possible to the moyamoya disease group. This observational cohort will undergo baseline clinical assessment, routine laboratory testing, 5T high-resolution MRI, and biospecimen collection. Planned enrollment: 100.	Diagnostic test: 5T High-Resolution MRI; 5T high-resolution MRI will be performed in all cohorts at baseline enrollment. During follow-up, repeat 5T MRI may be performed optionally in participants who are willing to return for imaging reassessment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incident Moyamoya Disease in First-Degree Relatives	Incident moyamoya disease occurring during follow-up in first-degree relatives of patients with moyamoya disease, confirmed by clinical diagnosis and imaging findings, including computed tomography angiography (CTA), magnetic resonance angiography (MRA), or digital subtraction angiography (DSA).	From enrollment through 3 years of follow-up
Recurrent Stroke or Transient Ischemic Attack in Participants With Moyamoya Disease	Occurrence of recurrent stroke or transient ischemic attack during follow-up in participants with moyamoya disease, confirmed by clinical evaluation and imaging findings when applicable.	From enrollment through 3 years of follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rehospitalization in Participants With Moyamoya Disease	Any rehospitalization related to moyamoya disease or its complications during follow-up in participants with moyamoya disease.	From enrollment through 3 years of follow-up
Repeat Surgery or Intervention in Participants With Moyamoya Disease	Any repeat surgical revascularization or other disease-related intervention during follow-up in participants with moyamoya disease.	From enrollment through 3 years of follow-up
Functional Outcome Assessed by Modified Rankin Scale	Functional outcome assessed using the Modified Rankin Scale, a 7-point scale ranging from 0 to 6, where 0 indicates no symptoms and 6 indicates death; higher scores indicate worse functional outcome.	At 3 years after enrollment

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2024
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2030

Study Registration Dates

• First Submitted: March 28, 2026
• First Submitted That Met QC Criteria: April 1, 2026
• First Posted (Actual): April 8, 2026

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Biomarkers; Multi-omics; Moyamoya Disease; Early Screening; Family-Based Cohort; High-Resolution MRI
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arterial Occlusive Diseases; Intracranial Arterial Diseases; Carotid Artery Diseases; Cerebral Arterial Diseases; Moyamoya Disease
• Other Study ID Numbers: 2026BJYYEC-KY030-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Individual participant data sharing is currently undecided. The study involves longitudinal clinical, imaging, biospecimen, and multi-omics data from patients with moyamoya disease, first-degree relatives, and healthy controls. Any future sharing of de-identified individual participant data will depend on institutional policy, ethics committee approval, participant consent, data privacy protection, and the development of an appropriate data access mechanism.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No