Insulin Sensitivity, Intestinal Failure, Osteoporosis
Conditions
Keywords
Parenteral Nutrition, Intestinal Failure, Circadian misalignment
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.
Interventions
DIETARY_SUPPLEMENTParenteral nutrition
Parenteral nutrition will be administered starting at 8 pm
Sponsors
Netherlands Organisation for Scientific Research
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Intervention model description
Randomized crossover pilot study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in glucose variability | 2 weeks versus 2 weeks | Changes in glucose variability measured by a continuous glucose monitor |
| Differences in bone turnover marker Procollagen 1 Intact N-Terminal Propeptide | Study day 1 versus study day 2 | Differences in the bone turnover marker Procollagen 1 Intact N-Terminal Propeptide (ug/L) |
| Differences in bone turnover marker carboxy-terminal collagen crosslinks | Study day 1 versus study day 2 | Differences in bone turnover marker carboxy-terminal collagen crosslinks (ng/L) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in nitrogen balance | Study day 1 versus study day 2 | Changes in nitrogen balance by comparing output (feces/urine) versus intake (oral/enteral/parenteral) |
| Changes in sleep/wake rhythm | 2 weeks versus 2 weeks | Changes in sleep/wake rhythm measured by an actigraph |
| Changes in sleep quality | 2 weeks versus 2 weeks | Changes in sleep quality, measured by Visual Analogue Scale (VAS) score (scale 1-10, higher scores mean better outcome) |
| Changes in energy expenditure | Study day 1 versus study day 2 | Changes in energy expenditure assessed by indirect calorimetry (kcal/24h) |
| Changes in substrate oxidation rates | Study day 1 versus study day 2 | Changes in substrate oxidation rates assessed by indirect calorimetry (percent) |
| Changes in clock gene expression | Study day 1 versus study day 2 | Changes in clock gene expression in leukocytes (if feasible; pilot) |
| Changes in plasma insulin | Study day 1 versus study day 2 | insulin (pmol/L) |
| Changes in plasma glucagon | Study day 1 versus study day 2 | glucagon (ng/L) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes in body temperature | Study day 1 versus study day 2 | Changes in body temperature measured by i-buttons (Celsius) |
Countries
Netherlands
Contacts
Primary ContactM.J.M. Serlie, professor
Backup ContactP.H.L.T. Bisschop, professor
Outcome results
None listed