SBIR-STTR Award

Circadian (daily) rhythms play a significant role in the efficacy and tolerability of cancer treatments in both rodents and humans. Disruption of circadian rhythms disturbs sleep and has been shown to result in poorer survivorship rates in cancer patients. Furthermore, evidence suggests that timing treatments and interventions with circadian considerations can improve outcomes. While knowledge of internal time holds much potential for the treatment of disease, measuring circadian rhythms in the lab can be time-consuming and expensive. One's typical behavior (e.g. normal wake and bed times) can provide a first-order estimate of circadian state, but individual genetic variation and disruption of the circadian clock from irregular light exposure will throw off this estimate. Light at night from screens, a particularly important factor to consider in monitoring circadian rhythms, is now more common and disruptive than ever. We have developed mobile applications for estimating circadian rhythms in a non-invasive way using mathematical models. The apps track motion and activity and use these factors to predict both light and the user's internal time in a way that accounts for disruptions to one's ?normal? schedule. We propose to develop a mobile app for cancer patients that recommends lighting interventions to correct disrupted circadian rhythms as well as the best times for drug consumption for optimal circadian effect. We furthermore propose to integrate this system into the home environments of patients to improve compliance. The proposed work will be directed toward adapting the math models and algorithms underlying our past work into a tool for cancer patients. The outcome will be a prototype app that tracks patient circadian rhythms and suggests interventions to steer their circadian clocks back in sync with their environment, promoting health and managing insomnia. A Phase I SBIR grant would be used to develop the app and assess its potential in a limited usability trial. A Phase II SBIR would extend the work by refining the app and testing it in a clinical trial.

Project Terms:
Algorithms; Back; base; Beds; Behavior; Biological Clocks; Businesses; Cancer Patient; cancer therapy; Charge; circadian pacemaker; Circadian Rhythms; Clinical Trials; Color; commercial application; Consumption; Data; Development; Disease; Educational Materials; eHealth; Environment; FDA approved; Feedback; Genetic Variation; Goals; Grant; health management; Health Promotion; Home environment; Hospitals; Human; improved; improved outcome; Individual; insight; Intervention; Knowledge; Lead; lifestyle intervention; Light; Lighting; Link; mathematical algorithm; mathematical model; Mathematics; Measures; Medicine; Michigan; mobile application; Monitor; Motion; Outcome; patient population; Patients; Pharmaceutical Preparations; Phase; Photophobia; Play; prototype; Quality of life; Recommendation; Research; Resources; Rodent; Role; Sales; Schedule; Sleep; Sleeplessness; Small Business Innovation Research Grant; smartphone Application; Suggestion; Survival Rate; survivorship; Symptoms; System; technological innovation; Technology; Testing; Time; tool; Toxic effect; Universities; usability; Work;

Cancer patients often experience disruptions to their body's internal, circadian clock over the course of treatment, which contribute to worsened side-effects and quality of life. These side-effects include cancer- related fatigue (CRF), which affects millions of patients and can persist for months to years after the end of treatment. Despite the pervasiveness of CRF, the guidelines for treating it are largely limited to exercise, cognitive behavioral therapy, and other psychosocial interventions, which present challenges of compliance, accessibility, and scalability. Light therapy, however, has a lower barrier to entry and has shown promise as a way of reducing symptoms of fatigue in cancer patients by targeting circadian pathways. Light is the primary input to the body's internal clock. By timing light exposure-- e.g., increasing morning light and decreasing light at night-- lighting interventions can bolster the clock, improving fatigue and consolidating sleep. The advantages of a more robust clock may also go beyond fatigue and sleep, as better outcomes in cancer patients are associated with less disrupted circadian rhythms. Despite the potential value in light interventions, several limitations have held back their wide-spread adoption as a treatment. There is limited awareness about how light timing affects the circadian clock, which is complicated by the fact that the clock's sensitivity to light changes over the course of the day. In addition, any lighting interventions need to be tailored to an individual's “personal time zone” (i.e., their circadian clock's current state) in order to be effective. Two individuals living in the same location may need light at markedly different times if their daily schedules are sufficiently different, or if one's circadian clock is much more disrupted than the other. The work in this proposal is a clinical trial to test an app (“SHIFT”) that recommends personalized lighting interventions to reduce fatigue in cancer patients. 138 patients will be recruited from the University of Michigan's Cancer Center and provided with the SHIFT app, as well as a pair of blue-blocking glasses and a Fitbit wearable device. The patients will be tracked longitudinally, with fatigue as the primary outcome, and sleep disturbances, sleep aid usage, mood, and anxiety as secondary outcomes. We expect to observe statistically significant differences in fatigue as a result of targeted lighting interventions. The final product will be a quantification of the SHIFT app's ability to improve fatigue in cancer patients and a roadmap for iteratively improving the app.

Public Health Relevance Statement:
PROJECT NARRATIVE Fatigue is a major problem for cancer patients, and one that can persist long after treatment ends. Recent work has demonstrated that light therapy may mitigate or reduce fatigue levels in both cancer patients and cancer survivors. This proposal seeks to assess how lighting interventions distributed through a mobile app affect fatigue, sleep, and quality of life across three populations of cancer patients.

Project Terms:
Adoption; Affect; Aftercare; Algorithms; Anxiety; Autologous Stem Cell Transplantation; Awareness; Back; base; Behavioral; Biological Clocks; Breast; Cancer Center; Cancer Patient; Cancer Survivor; cancer therapy; cancer type; Chronotherapy; circadian; Circadian Dysregulation; circadian pacemaker; Circadian Rhythms; Clinical Trials; Cognitive Therapy; Comprehensive Cancer Center; Computer software; Data; environmental change; Exercise; experience; Fatigue; Feedback; fitbit; Goals; Gold; Guidelines; Hygiene; improved; Individual; Inferior; Intervention; Light; Lighting; Link; Location; Malignant Neoplasms; Measures; Melatonin; metastatic colorectal; Methods; Michigan; mobile application; Moods; novel; Outcome; Participant; Pathway interactions; patient population; Patients; Phase; phase I trial; Phototherapy; Population; primary outcome; prospective; Prostate; Provider; psychosocial; Quality of life; Randomized Controlled Trials; Recommendation; recruit; reduce symptoms; repaired; Research; Risk; Schedule; secondary outcome; side effect; Sleep; Sleep disturbances; sleep quality; Small Business Innovation Research Grant; survival outcome; Symptoms; technological innovation; Testing; Therapeutic; Time; time use; Toxic effect; treatment response; Treatment Side Effects; Universities; Update; wearable device; Work