Muscle Wasting in Critically IllProBoNoNCT03587870
Protein Delivery in Intermittent and Continuous Enteral Nutrition in ICU Patients
A study testing Enteral nutrition with Fresubin Intensive in people with Muscle Wasting in Critically Ill, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial summary
Acute skeletal muscle wasting in ICU patients is associated with functional impairment and with increased risk of death. Of what we know today, physical disability can persist up to 5 years. Adequate nutrition is the basis for an optimal recovery for ICU patients and for prevention of muscle wasting. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Muscle Wasting in Critically Ill
- What is being tested?
- Enteral nutrition with Fresubin Intensive
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 113 participants
- Where
- 1 siteSwitzerland
- Study dates
- 25 Mar 2019to 13 Feb 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Informed Consent as documented by signature
- Adult patients (age 18 years or older)
- Expected ICU stay of five days or longer
- Expected enteral feeding during at least five days
Who cannot join
- Pregnancy or breast feeding (women of childbearing age are tested for high beta-human chorionic gonadotropin (hCG) in urine or serum upon ICU admission)
- Clinically significant chronic or acute kidney insufficiency with a glomerular filtration rate (GFR) <15.
- BMI ≤ 18 and ≥ 35.
- Intestinal perforation, peritonitis, intestinal fistula, necrosis or other contraindication to enteral diet
- Death or discharge before 48 hours of observation
- Noradrenaline ≥ 0.5 µg/kg bodyweight /min
Show all 10Show fewer
- Inherited and chronic skeletal muscle disease (e.g. Morbus Duchenne or other motoneuron disease)
- Paralysis (e.g. hemiplegia, tetraplegia and paraplegia)
- Immunosuppression
- Haematologic malignancy
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
University Hospital Basel, operative ICU
Basel, Canton of Basel-City, 4031
About this study
Official title: Protein Delivery in Intermittent and Continuous Enteral Nutrition in ICU Patients A Prospective, Randomised Controlled Pilot Study in Critical Ill Patients With a Protein-rich Formula
Acute skeletal muscle wasting in ICU patients is associated with functional impairment and with increased risk of death. Of what we know today, physical disability can persist up to 5 years. Adequate nutrition is the basis for an optimal recovery for ICU patients and for prevention of muscle wasting. Today, continuous feeding is still the standard enteral nutrition form for patients in the ICU to limit the incidence of aspiration. A study of Serpa et al. and Georgia et al. compared the continuous feeding versus a bolus nutrition with a feeding time of 30 - 60 minutes every 4 hours. They showed no statistical differences in complications between both groups.
ProBoNo is a prospective, randomized, controlled pilot study of critically ill patients with a protein- rich formula to explore the impact of continuous or intermittent bolus nutrition on muscle breakdown in ICU patients. The investigators would like to recruit 68 patients during the first 24 hours after surgical intensive care unit admission. Prior beginning of nutrition administration, and on the 7th day thereafter the investigators will perform a muscle biopsy and an ultrasound from the vastus lateralis muscle in both groups.
Read more
The primary outcome is the time from 6.00 am of the following day after admission until the patient reaches his daily protein's target quantity. Secondary outcomes include the diameter and densitiy of the hamstrings assessed by ultrasound and histology, the process of gastric residual volume, number of diarrhoea events and laboratory findings like glucose, urea and insulin like growth factor (IGF)-1, all compared between the two time points.
Intermittent feeding is not only more natural and could help to limit the muscle wasting in ICU patients, it is also easier to handle for the ICU caring medical team. A trial from Georgia et al. in 2007 compared continuous to intermittent enteral nutrition. They found that the intermittently fed patients reached their nutrition goal faster than those being continuously nourished. This might in part be explained by feeding interruptions in the continuous feeding regimen. Presumably, preoperative holding of tube feedings in the continuous nutrition group most commonly caused interruptions. Thus, independently from prevention of muscle breakdown, a bolus nutrition would be more attractive.
Read the detailed description
The relevance of early continuous or intermittent enteral feeding of critically ill patients has been discussed controversially in the last years. Today, continuous feeding is still the standard for enteral nutrition in the ICU. The continuous nutrition can prevent abdominal intolerance like vomiting, diarrhoea and aspiration. Pulmonary aspiration is the most dramatic consequence of enteral nutrition and can be limited by a continuous feeding as shown by a study in 2003. However, nutrition was started with a bolus of 125ml as baseline by force of gravity over 15 minutes. Compared to the continuous nutrition, this is considered much volume in a short time. Naturally, risk of gastric intolerance in this scenario is very high.
In other studies, a similar amount of nutrition was given over a longer period of time (30 - 60 minutes) every 4 hours. In each cohort (continuous and bolus), only one case of pulmonary aspiration or tube obstruction was detected. After this study, other trials with a similar result followed. In 2007 a trial of Georgia et al. showed no statistical differences in complications regarding tube feeding, no differences of diarrhoea, emesis or pneumonias between continuous and bolus nutrition. The feeding time for bolus nutrition is also a critical influential factor. When an intermittent feeding is given over a longer period of time (20-40 minutes), the incidence of nausea and vomiting has not increased.
Intermittent feeding is not only a good alternative to continuous feeding, but also more natural, as long-term intake of nutrition over 20 hours is not common in any mammal. The alimentary tract and metabolic pathways of humans seem designed for intermittent ingestion of essential nutrients reduced to a few times a day. Different hormones of the endocrine cells affect complex roles of gastrointestinal motility, gall bladder contraction and nutrient absorption. The level of these hormones depends on the amount of nutrient ingestion. This response of the hormones is almost completely abolished in continuous feeding. But in intermittent nutrition, hormones like incretin, glucose-dependent insulinotropic polypeptide (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) boost the level of insulin and the resulting carbohydrate load and therefore influence the muscle protein synthesis and breakdown.
In healthy individuals, the anabolic effects of feeding occur due to an increase on the synthetic rate of muscle protein synthesis of approximately 300% with a simultaneous 50% decrease in the rate of protein breakdown. Two studies of 2009 and 2011 compared the intermittent bolus and continuous feeding and the effect of protein synthesis in skeletal muscle in neonatal pigs. They analysed the fractional rates of protein synthesis in muscle samples of continuous and intermittent bolus feeding groups. They could show that although both groups, continuous and intermittent bolus feeding, stimulate muscle protein synthesis, but in the bolus-fed, in the fractional rates of protein synthesis called K's was greater after a meal.
An ongoing study wants to show the effect of bolus vs. continuous feeding in ICU patients related to muscle wasting by measurements of ultrasound and blood samples. In this trial, the investigators would like to have a similar approach but with different measurements. Using ultrasound and muscle biopsies, the investigators aim to determine whether intermittent enteral feeding could preserve muscle mass better or more than standard continuous enteral feeding in the critically ill patients. In addition, the investigators would like to assess if intermittent bolus feeding optimizes protein intake in the first 7 days of critical illness since the intermittent route is less affected by interruptions following treatment and diagnostic procedures.
- Conditions
- Muscle Wasting in Critically Ill
- Being tested
- Enteral nutrition with Fresubin Intensive
- Keywords
- intensive care unit, intermittent enteral nutrition, continuous enteral nutrition, muscle wasting
- Medical subject headings
- Muscular Atrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Enteral nutrition with Fresubin IntensiveOther
Comparison of intermittent (experimental) vs continuous (standard, active comparator) enteral nutrition on muscle wasting in critically ill patients
| Study group | Role | What they receive |
|---|---|---|
| Bolus enteral nutrition with Fresubin Intensive | Experimental | Bolus nutrition over 30-40 minutes every 4 hours with Fresubin Intensive Receives: Other: Enteral nutrition with Fresubin Intensive |
| Continuous enteral nutrition with Fresubin Intensive | Active comparator | Continuous nutrition over 20 hours per day with Fresubin Intensive (standard) Receives: Other: Enteral nutrition with Fresubin Intensive |
What is being measured
The primary outcome is the main question the study is designed to answer.
Daily protein target quantity
Is the time from 6.00 am of the following day after admission until the patient reaches his daily protein target quantity (1.2 g/ kg Biologische Wertigkeit (BW)/ biological value protein in the control group, to 1.5 g/kg BW protein in the experimental group).
Measured: During ICU stay for the duration of 7 days after study inclusion
Secondary outcomes (6)
Diameter of the hamstrings
Diameter of the hamstrings assessed by ultrasound and histology
Measured: During ICU stay, exactly 7 days after study inclusion
Gastric residual content
Amount of gastric residual volume (ml)
Measured: Every day during ICU stay for the duration of 7 days after study inclusion
Diarrhoea
Number of diarrhoea events
Measured: Every day during ICU stay for the duration of 7 days after study inclusion
Glucose (mmol/l) measurement
Laboratory parameters relevant to assess under enteral Nutrition (Glucose (mmol/l))
Measured: Every day during ICU stay for the duration of 7 days after study inclusion
BUN (mg/dl) measurement
Laboratory parameters relevant to assess under enteral Nutrition (BUN (mg/dl))
Measured: Every day during ICU stay for the duration of 7 days after study inclusion
IGF-1 (mmol/l) measurement
Laboratory parameters relevant to assess under enteral Nutrition (IGF-1 (mmol/l))
Measured: Every day during ICU stay for the duration of 7 days after study inclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2018
- Study start25 Mar 2019
- Primary completion13 Feb 2026
- Study completion13 Feb 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Muscle Wasting in Critically IllStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A prospective, randomised controlled pilot study in critical ill patients with a protein-rich formula
- Masking
- None (open label)
- Enrolment
- 113 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alexa Hollinger, MD, Principal investigator, University Hospital Basel, Basel Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03587870
- Sponsor's protocol ID
- EKNZ 2018-00259
- Acronym
- ProBoNo
- Status last verified
- Jun 2026
- First submitted
- 4 Jun 2018
- Last updated
- 18 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Reinhold S, Yeginsoy D, Hollinger A, Todorov A, Tintignac L, Sinnreich M, Kiss C, Gebhard CE, Kovacs B, Gysi B, Imwinkelried L, Siegemund M. Protein delivery in intermittent and continuous enteral nutrition with a protein-rich formula in critically ill patients-a protocol for the prospective randomized controlled proof-of-concept Protein Bolus Nutrition (Pro BoNo) study. Trials. 2020 Aug 25;21(1):740. doi: 10.1186/s13063-020-04635-1.
PubMed 32843075
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Protein Delivery in Intermittent and Continuous Enteral Nutrition in ICU Patients A Prospective, Randomised Controlled Pilot Study in Critical Ill Patients With a Protein-rich Formula
- ClinicalTrials.gov ID
- NCT03587870
- Acronym / sponsor ID
- ProBoNo / EKNZ 2018-00259
- Conditions
- Muscle Wasting in Critically Ill
- Keywords
- intensive care unit, intermittent enteral nutrition, continuous enteral nutrition, muscle wasting
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 113 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- 25 Mar 2019 (actual)
- Primary completion
- 13 Feb 2026 (actual)
- Study completion
- 13 Feb 2026 (actual)
- First posted
- 16 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Acute skeletal muscle wasting in ICU patients is associated with functional impairment and with increased risk of death. Of what we know today, physical disability can persist up to 5 years. Adequate nutrition is the basis for an optimal recovery for ICU patients and for prevention of muscle wasting. Today, continuous feeding is still the standard enteral nutrition form for patients in the ICU to limit the incidence of aspiration. A study of Serpa et al. and Georgia et al. compared the continuous feeding versus a bolus nutrition with a feeding time of 30 - 60 minutes every 4 hours. They showed no statistical differences in complications between both groups.
ProBoNo is a prospective, randomized, controlled pilot study of critically ill patients with a protein- rich formula to explore the impact of continuous or intermittent bolus nutrition on muscle breakdown in ICU patients. The investigators would like to recruit 68 patients during the first 24 hours after surgical intensive care unit admission. Prior beginning of nutrition administration, and on the 7th day thereafter the investigators will perform a muscle biopsy and an ultrasound from the vastus lateralis muscle in both groups.
The primary outcome is the time from 6.00 am of the following day after admission until the patient reaches his daily protein's target quantity. Secondary outcomes include the diameter and densitiy of the hamstrings assessed by ultrasound and histology, the process of gastric residual volume, number of diarrhoea events and laboratory findings like glucose, urea and insulin like growth factor (IGF)-1, all compared between the two time points.
Intermittent feeding is not only more natural and could help to limit the muscle wasting in ICU patients, it is also easier to handle for the ICU caring medical team. A trial from Georgia et al. in 2007 compared continuous to intermittent enteral nutrition. They found that the intermittently fed patients reached their nutrition goal faster than those being continuously nourished. This might in part be explained by feeding interruptions in the continuous feeding regimen. Presumably, preoperative holding of tube feedings in the continuous nutrition group most commonly caused interruptions. Thus, independently from prevention of muscle breakdown, a bolus nutrition would be more attractive.
Detailed description
The relevance of early continuous or intermittent enteral feeding of critically ill patients has been discussed controversially in the last years. Today, continuous feeding is still the standard for enteral nutrition in the ICU. The continuous nutrition can prevent abdominal intolerance like vomiting, diarrhoea and aspiration. Pulmonary aspiration is the most dramatic consequence of enteral nutrition and can be limited by a continuous feeding as shown by a study in 2003. However, nutrition was started with a bolus of 125ml as baseline by force of gravity over 15 minutes. Compared to the continuous nutrition, this is considered much volume in a short time. Naturally, risk of gastric intolerance in this scenario is very high.
In other studies, a similar amount of nutrition was given over a longer period of time (30 - 60 minutes) every 4 hours. In each cohort (continuous and bolus), only one case of pulmonary aspiration or tube obstruction was detected. After this study, other trials with a similar result followed. In 2007 a trial of Georgia et al. showed no statistical differences in complications regarding tube feeding, no differences of diarrhoea, emesis or pneumonias between continuous and bolus nutrition. The feeding time for bolus nutrition is also a critical influential factor. When an intermittent feeding is given over a longer period of time (20-40 minutes), the incidence of nausea and vomiting has not increased.
Intermittent feeding is not only a good alternative to continuous feeding, but also more natural, as long-term intake of nutrition over 20 hours is not common in any mammal. The alimentary tract and metabolic pathways of humans seem designed for intermittent ingestion of essential nutrients reduced to a few times a day. Different hormones of the endocrine cells affect complex roles of gastrointestinal motility, gall bladder contraction and nutrient absorption. The level of these hormones depends on the amount of nutrient ingestion. This response of the hormones is almost completely abolished in continuous feeding. But in intermittent nutrition, hormones like incretin, glucose-dependent insulinotropic polypeptide (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) boost the level of insulin and the resulting carbohydrate load and therefore influence the muscle protein synthesis and breakdown.
In healthy individuals, the anabolic effects of feeding occur due to an increase on the synthetic rate of muscle protein synthesis of approximately 300% with a simultaneous 50% decrease in the rate of protein breakdown. Two studies of 2009 and 2011 compared the intermittent bolus and continuous feeding and the effect of protein synthesis in skeletal muscle in neonatal pigs. They analysed the fractional rates of protein synthesis in muscle samples of continuous and intermittent bolus feeding groups. They could show that although both groups, continuous and intermittent bolus feeding, stimulate muscle protein synthesis, but in the bolus-fed, in the fractional rates of protein synthesis called K's was greater after a meal.
An ongoing study wants to show the effect of bolus vs. continuous feeding in ICU patients related to muscle wasting by measurements of ultrasound and blood samples. In this trial, the investigators would like to have a similar approach but with different measurements. Using ultrasound and muscle biopsies, the investigators aim to determine whether intermittent enteral feeding could preserve muscle mass better or more than standard continuous enteral feeding in the critically ill patients. In addition, the investigators would like to assess if intermittent bolus feeding optimizes protein intake in the first 7 days of critical illness since the intermittent route is less affected by interruptions following treatment and diagnostic procedures.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- A prospective, randomised controlled pilot study in critical ill patients with a protein-rich formula
| Arm | Type | Receives |
|---|---|---|
| Bolus enteral nutrition with Fresubin Intensive | Experimental | Other: Enteral nutrition with Fresubin IntensiveBolus nutrition over 30-40 minutes every 4 hours with Fresubin Intensive |
| Continuous enteral nutrition with Fresubin Intensive | Active comparator | Other: Enteral nutrition with Fresubin IntensiveContinuous nutrition over 20 hours per day with Fresubin Intensive (standard) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Informed Consent as documented by signature
- Adult patients (age 18 years or older)
- Expected ICU stay of five days or longer
- Expected enteral feeding during at least five days
Key exclusion criteria (10 listed)
- Pregnancy or breast feeding (women of childbearing age are tested for high beta-human chorionic gonadotropin (hCG) in urine or serum upon ICU admission)
- Clinically significant chronic or acute kidney insufficiency with a glomerular filtration rate (GFR) <15.
- BMI ≤ 18 and ≥ 35.
- Intestinal perforation, peritonitis, intestinal fistula, necrosis or other contraindication to enteral diet
- Death or discharge before 48 hours of observation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Enteral nutrition with Fresubin IntensiveComparison of intermittent (experimental) vs continuous (standard, active comparator) enteral nutrition on muscle wasting in critically ill patients | Other | Bolus enteral nutrition with Fresubin Intensive, Continuous enteral nutrition with Fresubin Intensive |
Primary outcome
Daily protein target quantity
Time frame: During ICU stay for the duration of 7 days after study inclusion
Is the time from 6.00 am of the following day after admission until the patient reaches his daily protein target quantity (1.2 g/ kg Biologische Wertigkeit (BW)/ biological value protein in the control group, to 1.5 g/kg BW protein in the experimental group).
6 secondary outcomes
Diameter of the hamstrings
Time frame: During ICU stay, exactly 7 days after study inclusion
Gastric residual content
Time frame: Every day during ICU stay for the duration of 7 days after study inclusion
Diarrhoea
Time frame: Every day during ICU stay for the duration of 7 days after study inclusion
Glucose (mmol/l) measurement
Time frame: Every day during ICU stay for the duration of 7 days after study inclusion
BUN (mg/dl) measurement
Time frame: Every day during ICU stay for the duration of 7 days after study inclusion
IGF-1 (mmol/l) measurement
Time frame: Every day during ICU stay for the duration of 7 days after study inclusion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2026.
- Derived from this study: PubMed 32843075Reinhold S, Yeginsoy D, Hollinger A, Todorov A, Tintignac L, Sinnreich M, Kiss C, Gebhard CE, Kovacs B, Gysi B, Imwinkelried L, Siegemund M. Protein delivery in intermittent and continuous enteral nutrition with a protein-rich formula in critically ill patients-a protocol for the prospective randomized controlled proof-of-concept Protein Bolus Nutrition (Pro BoNo) study. Trials. 2020 Aug 25;21(1):740. doi: 10.1186/s13063-020-04635-1.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alexa Hollinger, MD principal investigator
University Hospital Basel, Basel Switzerland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Enteral nutrition with Fresubin Intensive in people with Muscle Wasting in Critically Ill, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Daily protein target quantity (time frame: During ICU stay for the duration of 7 days after study inclusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03587870, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2026.