Summary of project PR000678
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000678. The data can be accessed directly via it's Project DOI: 10.21228/M81Q26 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR000678 |
| Project DOI: | doi: 10.21228/M81Q26 |
| Project Title: | Mayo Pilot and Feasibility: A pilot study of urine metabolomics towards an outpatient estimate of circadian phase |
| Project Summary: | Although the effectiveness of several therapeutic interventions depend critically on their timing with respect to circadian phase, including the timing of light therapy for circadian rhythm sleep disorders, medications for high blood pressure, and chemotherapy treatments for cancer, no clinical test is available to reliably measure circadian phase rapidly, inexpensively, and non-invasively. This project will therefore provide the essential first steps toward the development and validation of a clinical test to estimate circadian phase from a single urine void via the identification of multiple rhythmic metabolites in urine using untargeted metabolomic profiling methods. Current methods to assess circadian phase in urine require serial measurement of a single compound (e.g., 6-sulphatoxymelatonin, the urinary metabolite of melatonin) over a 24- to 48-hour sampling window. Our approach proposes to assess many compounds in one sample to estimate circadian phase, based on the phase relationships across multiple parameters, an approach that is supported by our theoretical modeling framework. Using the untargeted metabolomics profiling services offered by the Mayo Clinic Metabolomics Resource Core, we will examine the 48-hour profiles of ~300 metabolites identified from urine samples collected in a randomly selected pilot sample of 12 healthy young volunteers (from >200 subjects) studied on an inpatient laboratory protocol that included both an ambulatory condition (i.e., habitual sleep-wake times under ordinary room light) and a constant routine procedure, the gold standard method for assessing circadian rhythms (i.e., 50-hour period during which subjects remain awake in a semi-recumbent posture in bed under dim light with equicaloric snacks served hourly). Cosinor analysis will be employed to determine which identified metabolites exhibit circadian rhythmicity, and comparisons between ambulatory and constantroutine conditions will further identify which metabolites are influenced by external factors such as sleep, meal timing, light, and posture. Finally, we will employ our theoretical modeling framework to estimate circadian phase from a single urine void using the concentration ratios of multiple metabolites that exhibit reliable and robust circadian rhythmicity. The accuracy of estimated circadian phase will be determined by comparison to actual circadian phase as defined by the peak of the 6-sulphatoxymelatonin rhythm. Once this approach has been established in a pilot set of subjects, future studies will focus on validation and testing of this approach in other data from our repository, including healthy young volunteers who have undergone rapid phase shift due to changes in sleep-wake schedule (i.e., simulated shift work) or in response to bright light exposure; patients with insomnia, who exhibit an 8-hour range in circadian phase; and blind participants without light perception, who exhibit non-entrained rhythms. Future studies will also test the efficacy of this method to a priori estimate circadian phase in patient populations that may benefit from improvements in circadian timing of treatment. The current proposal therefore represents the first essential step in developing a tool that can revolutionize medicine by adding an accurate measure of internal time – circadian medicine – into standard clinical practice. |
| Institute: | Mayo Clinic |
| Last Name: | Hilaire |
| First Name: | Melissa |
| Address: | 221 Longwood Avenue, Suite BL438 Boston, Massachusetts 02115 |
| Email: | msthilaire@rics.bwh.harvard.edu |
| Phone: | 617-732-4013 |
Summary of all studies in project PR000678
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST001002 | A pilot study of urine metabolomics in two female and one male subject towards an outpatient estimate of circadian phase using urine storage as a factor (part II) | Homo sapiens | Mayo Clinic | MS* | 2022-12-15 | 1 | 516 | Uploaded data (18.9M) |
| ST001003 | A pilot study of urine metabolomics in a female subject towards an outpatient estimate of circadian phase (part I) | Homo sapiens | Mayo Clinic | MS* | 2022-12-15 | 1 | 100 | Uploaded data (2.7M) |
