Clinical Trial: Identification of Novel Circadian Biomarkers

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Identification of Novel Circadian Biomarkers

Brief Summary: Circadian clocks are not only found in discrete areas of the brain, but are found in virtually every organ in our bodies, including the heart, lungs and immune system. Disruptions in circadian clocks, or chronopathology, may underlie various forms of cardiovascular, pulmonary, and metabolic disorders. Over the past two decades, molecular geneticists have "cracked" the clock to reveal its core biochemical mechanisms evident in organisms from fruit flies to humans. These mechanistic insights have led to the discovery of links between clock function and an ever-expanding array of prevalent diseases, including heart, lung, metabolic and sleep disorders. Yet the prevalence of circadian disruption in these patient populations is unclear because current tests are not easily applied in clinical settings or have yet to be developed. Here the investigators exploit our newfound understanding of clock mechanisms and the development of new genomic technologies to identify novel complements of clock-regulated genes ("signatures") that will reveal the state of the internal biological clock. This approach will allow us to take a genomic snapshot of clock status from a single blood draw, substantially easing the diagnosis of these individuals with evidence of circadian disruption or misalignment, i.e., chronopathology.

Detailed Summary:

Circadian clocks are not only found in discrete areas of the brain, but are found in virtually every organ in our bodies, including the heart, lungs and immune system. Disruptions in circadian clocks, or chronopathology, may underlie various forms of cardiovascular, pulmonary, and metabolic disorders. Over the past two decades, molecular geneticists have "cracked" the clock to reveal its core biochemical mechanisms evident in organisms from fruit flies to humans. These mechanistic insights have led to the discovery of links between clock function and an ever-expanding array of prevalent diseases, including heart, lung, metabolic and sleep disorders. Yet the prevalence of circadian disruption in these patient populations is unclear because current tests are not easily applied in clinical settings or have yet to be developed. Perhaps the major limitation of these techniques is the need for serial sampling over extended periods of at least 24 hours and in some cases longer. The development of an assay from a single blood draw would represent a major step forward, facilitating assessments of circadian disruption in a range of diseases.

An alternative strategy to existing assays is to use genomic microarrays to analyze circadian rhythms. Many studies in a number of organisms as well as multiple organs and tissues have found that substantial fractions of the genome (2-10%) are under robust circadian clock control. Importantly, these hundreds of rhythmic genes exhibit expression peaks at all times throughout the day, presumably reflecting their time-of-day specific functions. Using this as a foundation, Ueda and colleagues proposed an alternative strategy that would allow assessment of circadian time from a single blood draw allowing more routine assessments of circadian clock state. In brief, they identified the complement of rhythmic genes in livers of mice. They the
Sponsor: Northwestern University

Current Primary Outcome: Circadian gene expression profile [ Time Frame: 1 day ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Northwestern University

Dates:
Date Received: November 6, 2014
Date Started: December 2014
Date Completion: December 2018
Last Updated: September 22, 2016
Last Verified: September 2016