First we want to determine whether early high protein intake, using an enteral whey protein supplement, in addition to a standardized exercise training program and standard enteral nutrition preserves: a) in vitro skeletal muscle function in…
ID
Source
Brief title
Condition
- Muscle disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Our primary endpoint will be In vitro loss of skeletal muscle function measured
by contractility of individual muscle fibers between day 1-3 after inclusion
and 7 days later (day 8-10). Contractility parameters include maximal force,
calcium sensitivity of force, and myosin-actin kinetics.
Long- (between day 1-3 and day 28) and short term (between day 1-3 and day
8-10) loss of in vivo muscle mass will be assessed with bio-impedance analysis,
B-mode ultrasound of the m. quadriceps femoris and diaphragm thickness.
Clinical (in vivo) muscle function on day 1 (if feasible), 8-10 and 28 will be
measured with Medical Research Council (MRC) sum score, handgrip
strength,Maximal inspiratory and expiratory force and Short Physical
Performance Battery test. Also markers of systemic inflammation, change in
muscle morphology, day-28 clinical outcome and quality of life, and safety will
be investigated.
Secondary outcome
1) To determine whether leucine-rich high protein intake, in addition to
standardized exercise and standard enteral nutrition:
- Preserves short- and long-term in vivo muscle function and mass, and clinical
outcomes and quality of life in critically ill patients
- Increases muscle protein synthesis and attenuates activation of the
Ubiquitin-Proteasome pathway in critically ill patients.
2) To determine the relation between clinical markers for muscle function (e.g.
MRC) and in vitro muscle function.
Background summary
Muscle wasting has an enormous impact on long-term physical performance and
quality of life of intensive care survivors. Limitation of muscle wasting might
therefore improve physical performance and quality of life. In non-critically
ill patients, the combination of protein and exercise seems to improve muscle
strength and well-being. However, data on high protein nutritional intake in
addition to a standardized exercise training program to prevent skeletal muscle
wasting during critical illness are lacking. We have the unique experience and
expertise to isolate single muscle fibres from muscle biopsies and assess in
vitro their contractile capacity in combination with a clinical focus on muscle
and nutrition. This setting offers the opportunity to assess the potential
beneficial effect of high protein nutrition in addition to standardized
exercise training on in vitro and in vivo muscle mass and function. The
relation between clinical and in vitro markers of muscle mass and function will
bring novel insight that will aid in the development of new therapeutic
strategies.
Study objective
First we want to determine whether early high protein intake, using an enteral
whey protein supplement, in addition to a standardized exercise training
program and standard enteral nutrition preserves: a) in vitro skeletal muscle
function in critically ill patients during the first week of ICU admission and
b) short- and long-term in vivo muscle function and mass, clinical outcomes and
quality of life in critically ill patients. Secondly we want to determine
whether high protein intake, in addition to standardized exercise and standard
enteral nutrition, increases muscle protein synthesis and attenuates activation
of the Ubiquitin-Proteasome pathway in critically ill patients.
Study design
Multicenter, randomized controlled single-blinded randomised controlled trial.
All in vitro measurements and clinical muscle assessments will be performed by
a researcher or analyst blinded for group allocation. The whey protein
administration will not be blinded for the intensivist.
The trial will take place in the intensive care units of the participating
centers. These are mixed medical-surgical intensive care units. The expected
duration of the trial is 36 months.
Intervention
Group 1 (the intervention group) will receive, in addition to a standardized
exercise training program and standard enteral nutrition with a protein intake
of 1.0 g/kg/day, a whey protein supplement (high in leucine) to increase total
protein intake to a target of 1.5 g/kg/day. Group 2 (the control group) will
receive a standardized exercise training program and standard enteral nutrition
with a protein intake of 1.0 g/kg/day.
Study burden and risks
The burden associated with the study is related to the muscle biopsies, the
evaluation of muscle function, and the quality of life survey after 3 months.
Muscle biopsies will be taken twice (on day 1-3 and day 8-10) from m. vastus
lateralis using a Bergström needle (5 mm diameter). During the first biopsy,
patients will likely not notice the biopsy because they are sedated.
Furthermore, the area will be locally anesthetized, so the burden is mild. The
risk of haemorrhage at the muscle biopsy site is minimal because local pressure
can be given after the puncture. The risk of infection is negligible due to the
aseptic technique. The Physical Performance Battery (muscle function) takes
about 12 minutes in elderly patients. It includes a balance test, a 4-meter
walking test and rise from chair test. The 36-Item Short Form Health Survey
(SF-36) is a quality of life survey and interrogates the patient on daily
activities, pain, mood and health status. The burden of the ultrasound measures
of diaphragm thickness and m. quadriceps femoris on day 1-3, day 8-10 and day
28 is minimal, because echo is non-invasive and painless. The burden of
bioimpedance measurements is less than making an electrocardiogram (two
stickers on the hand and two on the feet). The total amount of blood sampled is
30 ml in 8 days (3 times 10 ml). The blood is taken from an existing arterial
or central venous line, so burden for the patients is negligible. The daily
standardised exercise program and daily physical examination are part of
standard physiotherapy and care.
Boelelaan 1117 kamer 7 B 85
Amsterdam 1081 HV
NL
Boelelaan 1117 kamer 7 B 85
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
Admitted to the intensive care unit; Age >= 18 years; On mechanical ventilation and expected to be mechanically ventilated for more than 72 hours after initiation of study; Expected to tolerate enteral nutrition and to require enteral nutrition for more than 72 hours; SOFA score >= 6 on admission day; Written informed consent of patient or legal representative.
Exclusion criteria
Contra-indication to enteral nutrition; Short bowel syndrome; Child C liver cirrhosis or acute liver failure; Dialysis dependency; Requiring other specific enteral nutrition for medical reason; BMI > 35 kg/m2; Extensive treatment limitations; Disseminated malignancy; Haematological malignancy; Primary neuromuscular pathology; Chronic use of corticosteroids for > 7 days before ICU admission; Contra-indication for muscle biopsy (need for uninterrupted systemic anticoagulation, PT >1.4 , Thrombocytes <100).
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL56628.029.16 |