Effect of Nocturnal Parenteral Nutrition on Bone Turnover and Energy Metabolism

Study Overview
=================
Brief Summary
-----------------
This clinical trial will study the effect of daytime versus nighttime parenteral nutrition on bone turnover, glucose variability, nitrogen balance, sleep and wake rhythm and peripheral clock gene expression in patients with chronic intestinal failure.

Detailed Description
-----------------
Objective: This randomized crossover pilot study aims to determine the effect of nocturnal versus daytime cyclic infusion of parenteral nutrition in adult patients with chronic intestinal failure on bone turnover, glucose metabolism, nitrogen balance, sleep and wake rhythm and clock genes expression. This study will include 20 adult patients with chronic intestinal failure. Patients will receive nocturnal parenteral nutrition for 2 weeks (period A) and will switch to daytime parenteral nutrition (period B) for 2 weeks (random assignment). During both study periods glucose variability and sleep / wake rhythm will be measured. After both study periods, patients will be admitted to the metabolic unit for 24 hours to measure bone turnover markers, nitrogen balance, glucoregulatory hormones, energy expenditure and substrate oxidation rates and clock gene expression in leukocytes.

Official Title
-----------------
The Effect of Parenteral Nutrition During Nighttime Versus Daytime on Bone Turnover and Energy Metabolism in Intestinal Failure Patients

Conditions
-----------------
Intestinal Failure, Osteoporosis, Insulin Sensitivity

Intervention / Treatment
-----------------
* Dietary Supplement: Parenteral nutrition
* Dietary Supplement: Parenteral nutrition


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Home parenteral nutrition for at least 5 nights a week On home parenteral nutrition for more than 1 year No major changes in parenteral nutrition for 3 months prior to inclusion Exclusion Criteria: Parenteral infusion for more than 16 h a day Use of bone modifying drugs in the last 2 years Bone fractures in the past year Renal insufficiency (eGFR < 60 ml/min) HbA1c ≥48 mmol/ml Use of corticosteroids Shift work Performing intensive exercise (> 2 hours a day and > 3 times a week)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized crossover pilot study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nocturnal parenteral nutrition<br>Patients will receive nocturnal parenteral nutrition, starting at 8pm | Dietary Supplement: Parenteral nutrition<br>* Parenteral nutrition will be administered starting at 8 pm<br>* Other names: active comparator;|
| Experimental: Diurnal parenteral nutrition<br>Patients will receive diurnal parenteral nutrition, starting at 8am | Dietary Supplement: Parenteral nutrition<br>* Parenteral nutrition will be administered starting at 8 am<br>* Other names: experimental;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in bone turnover marker Procollagen 1 Intact N-Terminal Propeptide | Differences in the bone turnover marker Procollagen 1 Intact N-Terminal Propeptide (ug/L) | Study day 1 versus study day 2 | 
| Differences in bone turnover marker carboxy-terminal collagen crosslinks | Differences in bone turnover marker carboxy-terminal collagen crosslinks (ng/L) | Study day 1 versus study day 2 | 
| Changes in glucose variability | Changes in glucose variability measured by a continuous glucose monitor | 2 weeks versus 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in plasma insulin | insulin (pmol/L) | Study day 1 versus study day 2 | 
| Changes in plasma glucagon | glucagon (ng/L) | Study day 1 versus study day 2 | 
| Changes in nitrogen balance | Changes in nitrogen balance by comparing output (feces/urine) versus intake (oral/enteral/parenteral) | Study day 1 versus study day 2 | 
| Changes in sleep/wake rhythm | Changes in sleep/wake rhythm measured by an actigraph | 2 weeks versus 2 weeks | 
| Changes in sleep quality | Changes in sleep quality, measured by Visual Analogue Scale (VAS) score (scale 1-10, higher scores mean better outcome) | 2 weeks versus 2 weeks | 
| Changes in clock gene expression | Changes in clock gene expression in leukocytes (if feasible; pilot) | Study day 1 versus study day 2 | 
| Changes in energy expenditure | Changes in energy expenditure assessed by indirect calorimetry (kcal/24h) | Study day 1 versus study day 2 | 
| Changes in substrate oxidation rates | Changes in substrate oxidation rates assessed by indirect calorimetry (percent) | Study day 1 versus study day 2 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Parenteral Nutrition, Intestinal Failure, Circadian misalignment