Clinical and Genetic Evaluation of Individuals With Undiagnosed Disorders Through the Undiagnosed Diseases Network

• ClinicalTrials.gov Identifier: NCT02450851
• Recruitment Status: Recruiting
• First Posted: May 21, 2015
• Last Update Posted: January 30, 2023
• Sponsor: National Human Genome Research Institute (NHGRI)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )

Tracking Information

• First Submitted Date: May 19, 2015
• First Posted Date: May 21, 2015
• Last Update Posted Date: January 30, 2023
• Actual Study Start Date: September 16, 2015
• Estimated Primary Completion Date: December 31, 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 11, 2021)

• Improve the level of diagnosis and care for patients with undiagnosed diseases through the development of common and site-specific protocols designed by an enlarged community of investigators [ Time Frame: Inpatient stay Day 1-5 and followup ]
  Improve the level of diagnosis and care for patients with undiagnosed diseases through the development of common and site-specific protocols designed by an enlarged community of investigators.
• Facilitate research into the etiology of undiagnosed diseases, by collecting and sharing standardized, high-quality clinical and laboratory data including genotyping, phenotyping, and documentation of environmental exposures [ Time Frame: Inpatient stay Day 1-5 and followup ]
  Facilitate research into the etiology of undiagnosed diseases, by collecting and sharing standardized, high-quality clinical and laboratory data including genotyping, phenotyping, and documentation of environmental exposures.
• Create an integrated and collaborative research community across multiple clinical sites and between laboratory and clinical investigators prepared to investigate the pathophysiology of these new and rare diseases, the impact of the diagnostic p... [ Time Frame: Inpatient stay Day 1-5 and followup ]
  Create an integrated and collaborative research community across multiple clinical sites and between laboratory and clinical investigators prepared to investigate the pathophysiology of these new and rare diseases, the impact of the diagnostic process on patients and families, and share this understanding to identify improved options for optimal patient management.

• Original Primary Outcome Measures (submitted: May 19, 2015): Making a diagnosis [ Time Frame: Admission and ad hoc after that ]
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Clinical and Genetic Evaluation of Individuals With Undiagnosed Disorders Through the Undiagnosed Diseases Network
• Official Title: Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network

Brief Summary

Background:

- Without an explanation for severe and sometimes life-threatening symptoms, patients and their families are left in a state of unknown. The NIH helped create a network of medical research centers, called the Undiagnosed Diseases Network (UDN), to provide care and answers for these individuals.

Objectives:

- To improve diagnosis and care for people with undiagnosed diseases.

Eligibility:

- People with undiagnosed diseases, and their relatives.

Design:

• Participants will travel to one of the UDN medical centers for a 5-day clinical and research visit.

  • As part of the visit, UDN healthcare providers may ask participants to have:

    • Clinically indicated tests and procedures performed including:

      • A physical exam
      • Blood and urine tests
      • A review of health and family history
      • X-rays and body scans
      • Surveys
      • Photographs of the face and body
      • A special diet to see if the body can handle the food without having a reaction, like vomiting
      • Video or voice recordings
      • Other tests and procedures to help reach a diagnosis

    • Research tests and procedures performed including:

      • A skin biopsy. For this, a small piece of skin will be taken.
      • Surveys
      • Other tests and procedures for research that may not be related to a diagnosis or treatment.
• Most participants will be asked to give samples for genetic testing.
• Participants may be contacted after their visit to discuss test results. They may also be contacted in the future for interviews and surveys.
• Relatives of participants may be asked to give samples for genetic testing. They may be asked to have parts of their visit recorded and to have additional tests. They may also be contacted in the future for interviews and surveys.
• Clinical and research information collected will be stored in a database.
• Information and samples collected will be shared with others for research purposes.

• Detailed Description: Without an explanation for severe and sometimes life-threatening symptoms, patients and their families are left in a state of unknown. Many individuals find themselves being passed from physician to physician, undergoing countless and often repetitive tests in the hopes of finding answers and insight about what the future may hold. This long and arduous journey to find a diagnosis does not end for many patients- the Office of Rare Diseases Research (ORDR) notes that 6% of individuals seeking their assistance have an undiagnosed disorder. In 2008, the National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP) was established with the goal of providing care and answers for these individuals with mysterious conditions who have long eluded diagnosis. The NIH UDP is a joint venture of the NIH ORDR, the National Human Genome Research Institute Intramural Research Program (NHGRI-IRP), and the NIH Clinical Research Center (CRC). The goals of the NIH UDP are to: (1) provide answers for patients with undiagnosed diseases; (2) generate new knowledge about disease mechanisms; (3) assess the application of new approaches to phenotyping and the use of genomic technologies; and (4) identify potential therapeutic targets, if possible. Prior to formation of the Undiagnosed Diseases Network (UDN), the UDP had evaluated 3300 medical records, admitted 750 individuals with rare and undiagnosed conditions to the NIH Clinical Center, and identified more than 70 rare disease diagnoses and several new conditions. The success of the NIH UDP prompted the NIH Common Fund to support the establishment of a network of medical research centers, the UDN, for fiscal years 2013-2022. The clinical sites perform extensive phenotyping, genetic analyses, and functional studies of potential disease-causing variants. The testing performed on patients involves medically indicated studies intended to help reach a diagnosis, as well as research investigations that include a skin biopsy, blood draws, and DNA analysis. In addition, the UDN is furthering the goals of the UDP by permitting the sharing of personally identifiable phenotypic and genotypic information within the network. By sharing participant information and encouraging collaboration, the UDN hopes to improve the understanding of rare conditions and advance the diagnostic process and care for individuals with undiagnosed diseases.
• Study Type: Observational
• Study Design: Observational Model: Case-Only; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Individuals with undiagnosed conditions
• Condition: Genetic Disease
• Intervention: Not Provided

Study Groups/Cohorts

Undiagnosed disorders

Patients with rare, undiagnosed disorders.

Publications *

• Deuitch NT, Beckman E, Halley MC, Young JL, Reuter CM, Kohler J, Bernstein JA, Wheeler MT; Undiagnosed Diseases Network; Ormond KE, Tabor HK. "Doctors can read about it, they can know about it, but they've never lived with it": How parents use social media throughout the diagnostic odyssey. J Genet Couns. 2021 Dec;30(6):1707-1718. doi: 10.1002/jgc4.1438. Epub 2021 Jun 6.
• Walley NM, Pena LDM, Hooper SR, Cope H, Jiang YH, McConkie-Rosell A, Sanders C, Schoch K, Spillmann RC, Strong K, McCray AT, Mazur P, Esteves C, LeBlanc K; Undiagnosed Diseases Network; Wise AL, Shashi V. Characteristics of undiagnosed diseases network applicants: implications for referring providers. BMC Health Serv Res. 2018 Aug 22;18(1):652. doi: 10.1186/s12913-018-3458-2.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 8, 2019): 16000
• Original Estimated Enrollment (submitted: May 19, 2015): 8000
• Estimated Study Completion Date: December 31, 2028
• Estimated Primary Completion Date: December 31, 2028 (Final data collection date for primary outcome measure)

Eligibility Criteria

• INCLUSION CRITERIA:

• Ideal applicants to the UDN include individuals with:

  • One or more objective findings pertinent to the phenotype for which a UDN application was submitted.
  • No diagnosis despite evaluation by at least two specialists who assessed the patient for the objective finding(s).
  • Agreement for the storage and sharing of information and biomaterials, in an identified fashion amongst the UDN centers, and in a de-identified fashion to research sites beyond the network.
• Applicants unable to consent can be enrolled.

EXCLUSION CRITERIA:

-Applicants who are unlikely to be accepted include individuals with:

• Reported symptoms with no relevant objective findings.
• A diagnosis explaining objective findings.
• A diagnosis suggested on record review.
• Unwillingness to share data.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: up to 100 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Paul Mazur; (844) 746-4836; paul_mazur@hms.harvard.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02450851
• Other Study ID Numbers: 150130; 15-HG-0130
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )
• Original Responsible Party: Same as current
• Current Study Sponsor: National Human Genome Research Institute (NHGRI)
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: William A Gahl, M.D.; National Human Genome Research Institute (NHGRI)

• PRS Account: National Institutes of Health Clinical Center (CC)
• Verification Date: January 26, 2023