iKnow: A Prospective Study to Evaluate the Use of Multi-omics in Multi-System, Early Onset Disorders (iKnow)

Prospective observational study to further understand the value that a multi-omic approach has in individuals with a multi system, early onset disorder that does not have a molecular diagnosis by whole genome sequencing.

Study Overview

• Status: Active, not recruiting
• Conditions: Genetic Disease

Detailed Description

Understand the value and utilization of integrated multi-omics, in multi-system early onset disorders that have failed to yield findings by whole genome sequencing

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Strasburg, Pennsylvania, United States, 17579
      • Clinic for Special Children

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Outpatient setting with eighty percent consisting of prior negative genome cases that have previously received a clinical whole genome sequencing (cWGS) test. Remaining twenty percent will be positive controls who previously have a definitive diagnosis from clinical genetic testing.

Description

Inclusion Criteria:

• Undiagnosed probands must meet all of the following:

  1. Must be able to understand and sign an informed consent and speak, read, and write in their native language (if the subject is a minor, their parent must have these abilities)
  2. Proband between the ages of 12 months and 65 years
  3. Study consent and participation of at least two unaffected family members (biological parents preferred. One biological parent and unaffected sibling allowed)
  4. If applicable, unaffected sibling must be between the ages of 12 months and 65 years
  5. A high prior probability of a multi-system early onset undiagnosed genetic disorder based on an expert medical assessment
  6. Clinical WGS that did not yield a definitive diagnosis
  7. It is preferred but not required that ancestry is from an under-represented population in current clinical genetic and translational research data repositories, especially African American, Asian American and Native American
  8. Must be willing to have blood, urine and fecal samples taken to include participating family members

Diagnosed probands must meet all of the following:

1. Must be able to understand and sign an informed consent and speak, read, and write in their native language (if the subject is a minor, its Parent or Legally Authorized Representative must have these abilities).
2. Proband between the ages of 12 months and 65 years
3. Study consent and participation of at least two unaffected family members (biological parents preferred. One biological parent and unaffected sibling allowed)
4. If applicable, unaffected sibling must be between the ages of 12 months and 65 years
5. Known genetic cause(s) of disease, disorder, or phenotypic defect through prior clinical whole genome sequencing
6. It is preferred but not required that ancestry is from an under-represented population in current clinical genetic and translational research data repositories, especially African American, Asian American and Native American
7. Must be willing to have blood, urine and fecal samples taken to include participating family members

Exclusion Criteria:

• Undiagnosed probands must not meet any:

  1. Known non-genetic cause(s) of disease, disorder, or phenotypic defect
  2. Principal Investigator decides that the study is not in the best interest of the proband

Diagnosed probands must not meet any:

1. Principal Investigator decides that the study is not in the best interest of the proband

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Based on analysis of data from completed clinical utility evaluation surveys following receipt of study results by the PI, assess whether a patient's change of management resulted from the multi-omic results	Understand the value and utilization of integrated multi-omics, in multi-system early onset disorders that have failed to yield findings by whole genome sequencing	120 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of diagnoses yielded by each of the different orthogonally confirmed assay results	Assess the number of new diagnoses yielded by each approach	120 Days
Analyze data from completed clinical utility evaluation surveys; number of patients with change of management and whether the change was due to a diagnosis yielded by multiomic results	Analyze the clinical utility derived from a diagnosis	120 Days
Data utilization of multi-omic dataset for scientific community	Establish a multi-omic reference dataset from resource limited populations that can be used by the scientific community	120 Days

Collaborators and Investigators

• Sponsor: Illumina, Inc.
• Collaborators: Medical College of Wisconsin
• Investigators: Study Director: Ali Crawford, PhD, Illumina, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2021
• Primary Completion (Actual): December 10, 2021
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: September 9, 2021
• First Submitted That Met QC Criteria: September 9, 2021
• First Posted (Actual): September 20, 2021

Study Record Updates

• Last Update Posted (Actual): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 26, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn
• Other Study ID Numbers: ILMN-iKnow

Drug and device information, study documents

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