Clinical trial NCT03538639: Vascular Disease Discovery Protocol
Official title: Vascular Disease Discovery Protocol
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Vascular Dysfunction
Genetic Mutations
Genetic Predisposition
Keywords: 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
Natural History
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2018-05-29
Enrollment: 1000
Sex: ALL
Minimum age (years): 2
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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

Brief summary: 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

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.

Eligibility criteria: * 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.

Primary outcomes:
measure: 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...
timeFrame: ongoing
Secondary outcomes:
measure: 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...
timeFrame: ongoing
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Heart, Lung, and Blood Institute (NHLBI)
name: Manfred Boehm, M.D.
role: PRINCIPAL_INVESTIGATOR
References: