Vascular Disease Discovery Protocol

Background:

Some genetic diseases put increase the risk of heart and blood diseases, which are the number one cause of death and disability in the U.S. Researchers want to study diseases of the heart and/or blood vessels. They want to collect data and specimens from affected people, their family members, and healthy people.

Objective:

To study diseases of the heart and/or blood vessels.

Eligibility:

People age 2 and older who may have genetic disease affecting the heart and/or blood vessels Their relatives

Healthy volunteers

Design:

Participants will be screened with a medical history, physical exams, and imaging tests. Participants may have a few visits or visits for 2 weeks or more. This will depend on their age and disease status. Visits may include:

Photographs of the face and body

Heart tests

Samples taken of blood, urine, saliva, skin, and/or tissue

Scans. For some, a dye may be injected into a vein.

A six-minute walk test

Lung tests. For some, participants will blow into a tube. For others, they will breathe in a gas from a mask, have a small injection, then have a scan.

Stress tests while walking on a treadmill or riding a stationary bike

Ultrasound of veins and arteries

Devices outside the body testing the stiffness and function of arteries

Eye exam and eye tests. For some, a dye may be injected in a vein.

Blood pressure tests

Measurements of blood flow under the skin and in the arms and fingernail blood vessels

Devices outside the body testing flexibility of the blood vessels and skin, and skin temperature

Study Overview

• Status: Recruiting
• Conditions: Genetic Predisposition; Vascular Dysfunction; Genetic Mutations

Detailed Description

The NIH provides a unique opportunity for research scientists to participate in the bench-to-bedside process, which is essential for the full implementation of translational medicine programs. The study of rare monogenetic and undiagnosed diseases is a complex bedside-to-bench-to-bedside endeavor. Recent studies show that rare genetic variants are more likely than common variants to have deleterious effects on protein structure, function, and/or expression, possibly leading to clinically relevant events. Studies of large patient populations offer the opportunity to identify rare genetic variants underlying human disease and will have impactful implications for human health. We propose to characterize the etiology and natural history of rare and orphan diseases with vascular phenotypes. We will also study rare genetic modifiers and identify novel disease mechanisms contributing to common vascular diseases. Subsequent disease-related protocols may be developed based on findings from subjects enrolled in this protocol for further intensive natural history studies and potential innovative therapeutic studies. In addition to its role in investigating individuals who are of interest to the Translational Vascular Medicine Branch (TVMB) of the NHLBI, this protocol can provide a possible avenue for admitting subjects from other NIH programs, such as the NIH Undiagnosed Diseases Program, the Center for Human Immunology Trans-institute program or other NIH protocols where subjects exhibit vascular phenotypes.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Manfred Boehm, M.D.; Phone Number: (301) 435-7211; Email: boehmm@nhlbi.nih.gov
• Study Contact Backup: Name: William R Whalen, C.R.N.P.; Phone Number: (301) 402-9841; Email: william.whalen@nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: NIH Clinical Center Office of Patient Recruitment (OPR); Phone Number: TTY dial 711 800-411-1222; Email: ccopr@nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 100 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

We expect to enroll an unlimited number of subjects. The study population will be divided into groups that reflect both the potential studies that may be performed in distinct groups and the risk to benefit analysis for these groups. The appendices at the end of the protocol describe possible procedures and risk profiles for all the study subjects. Vulnerable populations, including pregnant women, children and cognitively impaired persons, may participate in this study. The groups include: 1.Adult index cases (affected) and relatives (affected and unaffected) 2.Child index cases (affected) and child relatives (affected and unaffected) 3.Healthy adult volunteers

Description

• INCLUSION CRITERIA:
• All subjects must be between the ages of 2-100 years old.
• Affected pregnant women if they have been referred with a known or suspected pathology or if they become pregnant while on study.
• Unaffected related pregnant women (including spouses/partners) for cord blood and tissue collection (surgical waste) only at the time of delivery.

EXCLUSION CRITERIA:

• Healthy volunteers unable to give informed consent
• Healthy volunteers who decline to have blood drawn and/or tissue studies or who do not consent to have samples stored for future research.
• Cognitively impaired individuals who are not affected.
• Cognitively impaired individuals not related to affected subjects.
• Unaffected unrelated pregnant women.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
1; Adult index cases (affected) and relatives (affected and unaffected)
2; Child index cases (affected) and child relatives (affected and unaffected)
3; Healthy adult volunteers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rapid initiation of new, disease-specific investigations to enable the collection of data and biospecimens on affected subjects, their family members and healthy controls, and to assist in the generation of diagnoses and further the understandin...	Understanding of disease pathophysiology in subjects with uncommon vascular disease presentation.	ongoing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
to improve diagnosis, identify biomarkers, develop outcome measures, create centers of expertise and provide the foundation for therapy development. Clinically indicated procedures may yield data that can be used to support or guide research obj...	to improve diagnosis, identify biomarkers, develop outcome measures, create centers of expertise and provide the foundation for therapy development. Clinically indicated procedures may yield data that can be used to support or guide research objectives.	ongoing

Collaborators and Investigators

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Manfred Boehm, M.D., National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2018
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): May 15, 2037

Study Registration Dates

• First Submitted: May 25, 2018
• First Submitted That Met QC Criteria: May 25, 2018
• First Posted (Actual): May 29, 2018

Study Record Updates

• Last Update Posted (Actual): August 21, 2026
• Last Update Submitted That Met QC Criteria: August 20, 2026
• Last Verified: August 19, 2026

More Information

Terms related to this study

• Keywords: Natural History; Etiology of Rare and Orphan Diseases with Vascular Phenotype; Natural History of Rare and Orphan Diseases with Vascular Phenotype; Pathophysiology of Uncommon Vascular Diseases; Undiagnosed Diseases; Rare Human Diseases with Vascular Features
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Disease Susceptibility; Pathological Conditions, Signs and Symptoms; Undiagnosed Diseases; Genetic Predisposition to Disease
• Other Study ID Numbers: 180108; 18-H-0108

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: It is not yet known

Drug and device information, study documents

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