Early Onset Genetic Conditions With Near Complete PenetranceGUARDIANNCT05990179
Genomic Uniformed-Screening Against Rare Disease In All Newborns
A study testing Genome sequencing-based newborn screening in people with Early Onset Genetic Conditions With Near Complete Penetrance, run by Columbia University at 1 site in United States.
Trial summary
The goal of this study is to learn how genomic sequencing technology can be used to effectively expand the conditions screened on newborn screening. Newborn screening ensures equity and allows all babies to have the same chance at the healthiest life. Read more about this study
- Who is it for?
- Ages 1 day to 1 monthHealthy volunteers can take part
- Conditions the study is for
- Early Onset Genetic Conditions With Near Complete Penetrance
- What is being tested?
- Genome sequencing-based newborn screening
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100,000 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Sep 2022to Sep 2029
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 1 month
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Newborns admitted to the well-baby nurseries from the recruiting hospitals
- Newborns born after 33 weeks of gestation
- Newborns whose parents are English, Mandarin, or Spanish speaking
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Columbia University Irving Medical Center/NYP
New York, New York, 10032
Anah Hetzler, 212-305-5508, ak3578@cumc.columbia.edu
Rudolph Leibel, MD
About this study
The goal of this study is to learn how genomic sequencing technology can be used to effectively expand the conditions screened on newborn screening. Newborn screening ensures equity and allows all babies to have the same chance at the healthiest life. Families will be invited to have their newborn baby screened for additional conditions beyond what all babies are screened for as part of the newborn screening public health program. Families can choose to be part of the study or choose not to be part of the study and just have the routine newborn screening test. Families will also be able to choose to learn about their baby's risk for conditions that have effective treatments available but are not on the routine newborn screening panel or also learn about conditions for which there is not currently FDA approved medications but for which medications are under development or for which early intervention services or treatment of seizures may improve the child's outcome. Families will be invited to the study shortly after the baby is born and will learn the decision not to participate, and we will interview a subset of parents who agree to be interviewed. Newborns who screen positive will be referred to appropriate providers for care and will be followed through review of electronic medical records and parental follow up via phone, text, postal mail or email.
Read the detailed description
Newborn screening (NBS) is the process of screening all newborns for select conditions shortly after birth. This process reduces morbidity and mortality by the detection of medically actionable conditions in pre-symptomatic newborns. Approximately 1 in every 180 newborns is diagnosed with a condition through NBS. NBS is a public health service; every infant regardless of health insurance or ability to pay is tested. NBS ensures equity and allows all babies to have the same chance at the healthiest life. Effective NBS requires coordination and collaboration from multiple stakeholders - the parents, the hospital of birth, state department of health lab, the pediatrician, and the specialty referral center.
Conditions included on the NBS must fulfill several criteria: 1) significant clinical benefit for the newborn early in life including treatment administered within the first few years of life, 2) readiness of public health departments to effectively screen for the condition, and 3) feasibility of successful implementation of population screening. In the United States, screening of newborns is under the purview of state public health departments. Each state decides which disorders to screen, and expansions to each state's panel of screened conditions. The federal government also plays a role through the Secretary of Health and Human Services (HHS) Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC). With rapid improvements in screening technology, diagnostic testing, and treatments, conditions not previously screened through NBS are being considered. Expanding NBS through genome-wide sequencing (GS) will be the most flexible and cost-effective way to add to what is currently in use.
- Being tested
- Genome sequencing-based newborn screening
- Keywords
- Newborn screening, Genome sequencing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Genome sequencing-based newborn screeningOther
Dried blood spots collected at birth for routine newborn screening will be used for genome sequencing based screening of a defined set of conditions.
| Study group | Role | What they receive |
|---|---|---|
| Enrolled in the study | Experimental | All newborns enrolled in the study will be evaluated. Receives: Other: Genome sequencing-based newborn screening |
What is being measured
The primary outcome is the main question the study is designed to answer.
Enrollment Rate (percentage)
Enrollment rate will be defined as: number of enrolled newborns / number of newborns approached by the research assistant.
Measured: From study launch to end of enrollment (up to 5 years)
Successful Sequencing Rate (percentage)
Successful sequencing rate will be defined as: number of successful sequencing / number of enrolled newborns.
Measured: Up to 6 months after the end of enrollment
Screen Positive Rate (percentage)
Screen positive rate will be defined as: number of newborns with a positive screening / number of successful sequencing.
Measured: Up to 6 months after the end of enrollment
True Positive Rate (percentage)
True positive rate will be defined as: number of confirmed diagnosis / number of screen positive.
Measured: Up to 6 months after the end of enrollment
Secondary outcomes (1)
Score on Decision Regret Scale
The Decision Regret Scale measures distress or remorse after a health care decision. This 5-items scale ranges from 0 (no regrets - best outcome) to 100 (highest regret - worst outcome). Scores above 1 and below 25 are considered as an indication of mild regret. Scores above 25 are considered as an indication of moderate to severe regret.
Measured: Up to 6 months after the end of enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2023
- Study start6 Sep 2022
- Primary completionSep 2029 (estimated)
- Study completionSep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Early Onset Genetic Conditions With Near Complete PenetranceStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- Illumina, Inc., GeneDx, New York State Department of Health
- Responsible party
- Principal investigator, Rudolph L. Leibel, Columbia University
- Investigators
- Wendy K. Chung, MD, PhD, Principal investigator, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05990179
- Sponsor's protocol ID
- AAAS9161
- Acronym
- GUARDIAN
- Status last verified
- Sep 2026
- First submitted
- 4 Aug 2023
- Last updated
- 21 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD will not be shared with other researchers.
Publications
Ziegler A, Koval-Burt C, Kay DM, Suchy SF, Begtrup A, Langley KG, Hernan R, Amendola LM, Boyd BM, Bradley J, Brandt T, Cohen LL, Coffey AJ, Devaney JM, Dygulska B, Friedman B, Fuleihan RL, Gyimah A, Hahn S, Hofherr S, Hruska KS, Hu Z, Jeanne M, Jin G, Johnson DA, Kavus H, Leibel RL, Lobritto SJ, McGee S, Milner JD, McWalter K, Monaghan KG, Orange JS, Pimentel Soler N, Quevedo Y, Ratner S, Retterer K, Shah A, Shapiro N, Sicko RJ, Silver ES, Strom S, Torene RI, Williams O, Ustach VD, Wynn J, Taft RJ, Kruszka P, Caggana M, Chung WK. Expanded Newborn Screening Using Genome Sequencing for Early Actionable Conditions. JAMA. 2025 Jan 21;333(3):232-240. doi: 10.1001/jama.2024.19662.
PubMed 39446378