Can Beta-Hydroxy-beta-Methylbutyrate Supplementation Counteract Muscle Catabolism in Critically Ill Patients?

Study Overview
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Brief Summary
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The rapid decline of muscle mass and function in mechanically ventilated critically ill patients is associated with prolonged length of mechanical ventilation, prolonged intensive care (ICU) and hospital stay, increased ICU and hospital mortality, and prolonged impairment in physical function and quality of life. High protein feeding only partially attenuates the muscle loss. The aim is to study the impact of HMB (3 g/day) on the muscle mass of the critically ill patients from day 4 of their admission to maximum 30 days, but at least for 10 days.

Detailed Description
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The rapid decline of muscle mass and function in mechanically ventilated critically ill patients is associated with poor outcome, and limitations of functional recovery. High protein feeding only partially attenuates the muscle loss. The aim is to study the impact of HMB (3 g/day) on the muscle mass of the critically ill patients from day 4 of their admission to maximum 30 days, but at least for 10 days. The study is testing a nutrition complement (HMB) that is included in feeding products registered for medical nutrition by Swiss Federal Authorities, but who do not provide sufficient protein quantities. On days 4 and 15 after ICU admission, specific investigations will include: Ultrasound measurement of the muscle quadriceps femoris (CSA), bioimpedance analysis (BIA) of body composition, protein synthesis and catabolism using amino acid tracers. On D30 and D60: telephone contact to assess global health and mobility (SF-12).

Official Title
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Can Beta-Hydroxy-beta-Methylbutyrate (HMB) Supplementation Counteract Muscle Catabolism in Critically Ill Patients? A Randomized Controlled Trial

Conditions
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Critical Illness, Muscle Weakness

Intervention / Treatment
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* Dietary Supplement: HMB (beta-hydroxy beta-methylbutyrate)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: likely length of stay >5 days on mechanical ventilation likely survival >7 days full treatment functional gastro-intestinal tract presence of a central venous catheter Exclusion Criteria: absence of consent less than 18 years patients gastro-intestinal dysfunction major burns >20% body surface admission for cardio-respiratory arrest or brain injury pregnancy or lactation diabetes mellitus (I and II) statin treatment patient on parenteral nutrition absence of central venous line participation in another interventional trial

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomised, double blind, controlled trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: HMB (beta-hydroxy beta-methylbutyrate)<br>HMB, 1.5 g b.i.d., from day 4 to day 30 after ICU admission | Dietary Supplement: HMB (beta-hydroxy beta-methylbutyrate)<br>* 1.5 g, b.i.d., by the enteral route, from Day 4 to Day 30 (minimum 10 days)<br>|
| Placebo Comparator: Placebo<br>Maltodextrin, 1.5 g b.i.d., from day 4 to day 30 after ICU admission | Dietary Supplement: HMB (beta-hydroxy beta-methylbutyrate)<br>* 1.5 g, b.i.d., by the enteral route, from Day 4 to Day 30 (minimum 10 days)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle mass of the thigh | Ultrasound cross sectional area of the thigh, to quantify muscle loss | Change between Day 4 and Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body composition | Bioelectrical impedance analysis (BIA): calculation of body compartments, lean body mass, and phase angle | Change between Day 4 and Day 15 | 
| Protein synthesis and breakdown | Multiple Amino acid tracer study: to detect chnges in protein metabolism between study start on day 4 and day 14 (i.e. after 10 days of intervention (HMB or placebo)) | Change between Day 4 and Day 15 | 
| Muscle strength (global and handgrip) | Medical Research Council muscle score (MRC) to assess upper and lower limb strength, and handgrip strength (not always feasible in ICU patients) and determine magnitude of strength loss | Measurements on Days 4, 15, and 30 | 
| Global Health and Mobility | Short Form 12 (SF-12) questionnaire to assess global health and mobility: range 12 to 56 points, the upper limit reflecting return to normal activity | on days 30 and 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Body composition, muscle mass, protein metabolism, enteral nutrition, ICU