Assessing Metabolic and Sleep Consequences of Overnight Home Parenteral Nutrition

Study Overview
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Brief Summary
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The purpose of this study is to determine whether advancing the timing of home parenteral nutrition from overnight to daytime regimens leads to improved glucose profiles and sleep quality, and other changes in plasma metabolic signatures.

Detailed Description
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Emerging evidence suggests that considering the time-of-day in clinical care may optimize health, partly through limiting sleep disruption and circadian misalignment. Acute sleep and circadian rhythms disturbances are associated with cardiometabolic derangements, including persistent hyperglycemia, a significant contributor to life-threatening complications. However, it is currently considered standard practice for patients on parenteral nutrition to be fed for 12-hour periods overnight. Current guidelines lack explicit guidance regarding the time-of-day when nutrition support should be administered. Thus, the overall objective of the clinical trial is to comprehensively examine a novel dimension of clinical nutrition by determining whether advancing the timing of home parenteral nutrition from overnight to daytime regimens leads to improved glucose profiles and sleep quality, and other changes in plasma metabolic signatures. The study is a 2-week controlled cross-over feeding trial where 20 short bowel syndrome patients will follow their usual overnight parenteral nutrition regimen for one week, and then advance their feeds to daytime for a second week. Patients will be assessed objectively using non-invasive, novel technologies and 'omics techniques. The investigators hypothesize that advancing the timing of home parenteral nutrition feeds to a daytime regimen is a cost-efficient, effective, and feasible nutrition timing countermeasure against metabolic derangements, fragmented sleep, and decreased quality of life. Results of this study may provide evidence-based, cost-efficient, and effective nutrition support countermeasures against hyperglycemia and sleep disruption, and could potentially modify current widespread clinical nutrition support practice.

Official Title
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Assessing Metabolic and Sleep Consequences of Overnight Home Parenteral Nutrition

Conditions
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Feeding Patterns, Sleep, Glucose Intolerance, Short Bowel Syndrome

Intervention / Treatment
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* Dietary Supplement: Time-of-day of parenteral nutrition provision


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult male or non-pregnant female volunteers (age 18-79) Short bowel syndrome diagnosis Able and willing to give consent and comply with study procedures Currently on routine home parenteral nutrition (at least 6 months) Exclusion Criteria: Blind, deaf or unable to speak English Women who are pregnant or nursing Diabetes diagnosis or currently taking or intending to take any diabetes medication or medications influencing sugars including oral glucocorticoids, growth hormone, erythropoietin, or chemotherapeutic Current use of sleep medication and melatonin With skin condition that precludes wearing sensors Within the last year, bariatric surgery or pregnancy Within the last one month, acute infections or illnesses requiring medical attention, hospitalizations, Emergency Department visits, blood transfusions, blood loss, blood donations Major changes in diet or physical activity level in the past 3 months Sleep and circadian disorders (such as obstructive sleep apnea and delayed sleep phase syndrome) Anticipated barriers or challenges to daytime and/or overnight cycled infusions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nighttime cycled parenteral feeds followed by daytime cycled parenteral feeds<br>Patients will follow nighttime feeding regimen for one week, and then advance their feeds (approximately 12 hours earlier) to daytime feeding regimen for one week. | Dietary Supplement: Time-of-day of parenteral nutrition provision<br>* Parenteral nutrition will be provided during the nighttime followed by daytime.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 24-hour average glucose from nighttime to daytime feeds | Glucose will be continuously measured using continuous glucose sensors. Blood glucose will be averaged during each of the two 1-week feeding regimens (nighttime and daytime). | Average values from days 1 to 7 (nighttime feeds) and days 8 to 14 (daytime feeds). | 
| Change in number of interruptions of sleep by physical movement assessed by actigraphy from nighttime to daytime feeds | Sleep will be objectively measured from actigraphy. The number of interruptions of sleep by physical movement will be calculated as 100 × the number of groups of consecutive mobile 30-s epochs/by the total number of immobile epochs. This measure will reflect sleep quality. | Actigraphy data from days 1 to 7 (nighttime feeds) and days 8 to 14 (daytime feeds). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in area under-the-curve of glucose from nighttime to daytime feeds | Glucose will be continuously measured using continuous glucose sensors. Area under-the-curve of blood glucose during the 12-hour feeds will be calculated using the trapezoid method and adjusted for baseline glucose values. Area under-the-curve of glucose will be averaged for each of the two 1-week feeding regimens (nighttime and daytime). | Glucose values from days 1 to 7 (nighttime feeds) and days 8 to 14 (daytime feeds) during 12-hour cycled feeds. | 
| Change in average daily duration of glucose levels above 140 mg/dl from nighttime to daytime feeds | Glucose will be continuously measured using continuous glucose sensors. Duration of glucose levels above 140 mg/dl will be averaged during each of the two 1-week feeding regimens (nighttime and daytime). | Average values from days 1 to 7 (nighttime feeds) and days 8 to 14 (daytime feeds). | 
| Change in fasting insulin concentration from nighttime to daytime feeds | Serum insulin will be measured from fasting blood samples collected on day 8 and 15. | Blood draw scheduled on days 8 and 15. | 
| Change in sleep duration from nighttime to daytime feeds | Sleep duration will be objectively measured from actigraphy and sleep logs. Duration will be averaged will be averaged during each of the two 1-week feeding regimens (nighttime and daytime). | Average values from days 1 to 7 (nighttime feeds) and days 8 to 14 (daytime feeds). | 
| Change in sleep midpoint from nighttime to daytime feeds | Sleep midpoint will be objectively measured from actigraphy and sleep logs. Midpoint will be averaged will be averaged during each of the two 1-week feeding regimens (nighttime and daytime). | Average values from days 1 to 7 (nighttime feeds) and days 8 to 14 (daytime feeds). | 
| Change in midpoint of least-active 5h timing from nighttime to daytime feeds | Measure of sleep timing as determined from actigraphy. Timing will be averaged will be averaged during each of the two 1-week feeding regimens (nighttime and daytime). | Average values from days 1 to 7 (nighttime feeds) and days 8 to 14 (daytime feeds). | 
| Change in midpoint of most-active 10h timing from nighttime to daytime feeds | Measure of sleep timing as determined from actigraphy. Timing will be averaged will be averaged during each of the two 1-week feeding regimens (nighttime and daytime). | Average values from days 1 to 7 (nighttime feeds) and days 8 to 14 (daytime feeds). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sleep, Parenteral Nutrition, Chrononutrition, Chronobiology, Nutrition Support, Metabolomics