# Urine metabolomics to estimate internal clock time

> **NIH NIH R21** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $223,750

## Abstract

Project Summary
The body’s internal clock (i.e., circadian rhythm) controls the timing of many aspects of physiology,
metabolism, and behavior. Disruption of circadian rhythms has been implicated in a surprisingly large number
of diseases, including many types of depression, autism, several types of cancer, and several
neurodegenerative disorders, and mounting evidence suggests that treatment for these diseases timed
optimally with respect to the body’s internal clock is critical to their effectiveness. There are two primary
barriers to implementing such “circadian-based” interventions in clinical practice, however. First, the timing of
the internal clock can vary by 5 to 8 hours in healthy individuals (even more variable in patient populations).
Thus, although many drugs are given based on time of day, e.g., morning vs. evening administration, a drug
administered at 8am in one individual may be administered at the biologically equivalent time of 3am in another
individual. Second, internal clock time is difficult to assess in a non-research setting. Current gold-standard
methods require serial measurement of a single compound that exhibits a robust circadian rhythm (e.g.,
melatonin) over a 24- to 48-hour sampling window, which is invasive, time-consuming and costly.
Instead of measuring one compound in serial samples, an alternate approach for assessing internal clock time
is to measure multiple compounds from a single sample. Recently, several groups have reported the ability to
assess internal clock time from multiple metabolite or transcriptomics rhythms measured from one or two blood
samples. While these methods represent a major advance in the ability to estimate internal clock time, blood
sampling remains invasive and the internal clock time derived from these methods is accurate only under
limited conditions. Here, we propose a metabolomics approach to assess internal clock time from a single
urine void. Our recent pilot analysis in n=3 participants has identified several candidate compounds from over
4,000 annotated metabolites detected by untargeted urine metabolomics profiling. The goal of this current
proposal is to confirm these candidate compounds in a larger sample size and test the ability of these
compounds to accurately assess internal clock time to within 30 minutes against a gold-standard measure.
The ability to assess internal clock time in a non-invasive and time- and cost-effective manner has direct

## Key facts

- **NIH application ID:** 10024088
- **Project number:** 5R21NR018974-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Melissa April St Hilaire
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $223,750
- **Award type:** 5
- **Project period:** 2019-09-25 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10024088

## Citation

> US National Institutes of Health, RePORTER application 10024088, Urine metabolomics to estimate internal clock time (5R21NR018974-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10024088. Licensed CC0.

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