Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05831592 |
| Other study ID # |
2022-A00581-42 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
February 23, 2023 |
| Est. completion date |
November 25, 2025 |
Study information
| Verified date |
February 2023 |
| Source |
Hopital Forcilles |
| Contact |
Aymeric LE NEINDRE, PhD |
| Phone |
+33160646093 |
| Email |
aleneindre[@]cognacq-jay.fr |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
In France, the prevalence of undernutrition in hospitalized patients varies from 30 to 50%.
Undernutrition is strongly associated with a decrease in the patient's functional abilities
and an increase in morbidity and mortality and healthcare expenses. In 2019, the Global
Leadership Initiative on Malnutrition (GLIM) published an international consensus report on
diagnostic criteria for undernutrition. The diagnostic criteria are numerous, and include
etiological criteria such as reduced food intake; an inflammatory setting; symptoms such as
anorexia, fatigue; phenotypic criteria such as weight loss, body mass index (BMI), fat to
lean mass ratio, fluid retention, and muscle function.
Muscle mass is described as a major diagnostic criterion, since it is on the one hand a
direct indicator of protein catabolism related to undernutrition, but also a reflection of
functional impairment in the patient, as it is directly associated with functional
capacities, autonomy and prognosis. Ultrasound is a reproducible method of muscle assessment.
It allows the evaluation of muscle thickness or cross-sectional area of a muscle, the
reduction of which, a marker of atrophy, is strongly correlated to its loss of strength and
to reference measurements. In addition, ultrasound can be used to assess muscle quality,
particularly by evaluating the echogenicity of the muscle. The echogenicity increases when
the muscle is altered, linked to the presence of fatty infiltrate and fibrous tissue. The use
of ultrasound in the evaluation of the patient's nutritional status, as a tool for assessing
muscle function, is developing in the ICU and is associated with an increase in the patient's
comorbidities. Studies remain limited to a few patient populations, do not report clear
cut-off values to define muscle pathological status, and require more precise definition of
ultrasound measurement protocols.
The investigators hypothesize that muscle ultrasound is reliable and valid in the evaluation
of muscle function during the screening of undernutrition in a population of patients
hospitalized in diabetology-obesity, pneumology, oncology and gastro-nutrition, under 70
years old.
Description:
1. Rationale 1.1 Epidemiology and morbidity of undernutrition Undernutrition, whether
related to disease, poverty, hunger, war or natural disasters, affects more than one
billion people worldwide. In France, an empirical estimate suggests a prevalence of
undernutrition among hospitalized patients of about 2 million or 30 to 50%. It should be
noted that undernutrition is very common in and out of hospital. It is widely accepted
that undernutrition can be caused by a deficit in nutrient intake or malabsorption.
However, it is now known that the inflammatory state present during illness is
associated with undernutrition.
1.2 International consensus on the definition of undernutrition
In 2019, the Global Leadership Initiative on Malnutrition (GLIM) published an
international consensus report on diagnostic criteria for undernutrition. The diagnostic
criteria are numerous, and include etiological criteria such as reduced food intake; an
inflammatory context; symptoms such as anorexia, fatigue; phenotypic criteria such as
weight loss, body mass index (BMI), fat to lean mass ratio, fluid retention, and muscle
function. GLIM has chosen to select the most relevant criteria among the etiological and
phenotypic criteria:
- Etiological criteria: reduced food intake and inflammatory state of the patient;
- Phenotypic criteria: weight loss, BMI, and reduced muscle mass. The presence of at
least one etiological criterion and one phenotypic criterion is mandatory to make
the diagnosis of undernutrition.
Muscle mass is described as a major diagnostic criterion, since it is on the one hand a
direct indicator of protein catabolism related to undernutrition, but also a reflection
of functional impairment in the patient, as it is directly associated with functional
capacities, autonomy and prognosis. Different measurement tools are suggested, such as
bioelectrical impedancemetry, ultrasound or magnetic resonance imaging, leaving the
choice of tool to the clinicians, depending on experience and local resources. Handgrip
measurement is considered a complementary measure.
GLIM recommends an assessment of the risk of undernutrition, using validated
questionnaires such as the NRS (Nutritional Risk Screening) or the MNA-SF (Mini
Nutritional Assessment- Short Form). The degree of severity of undernutrition is only
assessed on the basis of phenotypic criteria.
1.3 Roles of professionals in screening for undernutrition
In general, and more particularly in the Forcilles hospital, dieticians play a major
role in detecting undernutrition. They ensure a prospective watch on the patient's
admission to the hospital, with the collection of indicators related to BMI and weight
loss, in collaboration with the nurses and care assistants. They also carry out a
dietary consultation to clarify the above criteria, to evaluate the reduction of intake
and absorption, in collaboration with the physician, and the realization of body
composition measurements, such as bio-electrical impedancemetry. The evolution of the
definition of undernutrition, with an important place in the muscular and functional
evaluation of the patient, implies new actors: the physiotherapist and the Adapted
Physical Activity Teacher (APAT). Indeed, they have expertise in the evaluation of the
patient's muscular function and functional capacities. As part of their diagnostic
assessment, the physiotherapist is used to evaluating muscle function by dynamometry, as
well as the patient's functional capacities by field tests or the use of scores. The
EAPA also participates in the performance of field tests.
The collaboration between dieticians, physiotherapists, EAPAs, nurses, care assistants
and doctors thus makes it possible to meet the need to screen for undernutrition
according to this new definition.
1.4 Assessment of muscle function
Physical therapists and EAPAs use different tools to assess different aspects of muscle
function, such as strength or walking speed in more functional tests.
Isometric grip strength is strongly correlated with lower extremity muscle strength, and
is a pejorative marker of mobility in weakness. It has been observed a linear
relationship between grip strength and patient disability as measured by the Katz
independence scale. In addition, grip strength has been shown to be a good predictor of
the patient's clinical condition. The measurement of grip strength, using a dedicated
dynamometer, also has the advantage of being simple and reproducible and has reference
values adjusted for sex and BMI.
Gait speed is another indicator used to assess muscle function. It is associated with
lower limb strength and is a predictor of disability and mobility limitation. Usual
walking speed is most often measured over a distance of 4 or 6 m and has reference
values adjusted for sex and height.
Dietitians also participate in the evaluation of muscle function by measuring body
composition in terms of lean and fat mass. They perform bioelectrical impedancemetry,
which allows estimation of body fat and lean mass volumes by measuring the resistance of
biological tissues to a low-intensity, high-frequency sinusoidal electric current
through electrodes. This measurement method is simple to use, inexpensive, reproducible
and feasible in bedridden patients. It also correlates very well with MRI and reference
values are obtained in various adult populations.
1.5 Muscle ultrasound and undernutrition
Ultrasound is a reproducible method of muscle assessmen. It allows the assessment of
muscle thickness or cross-sectional area of a muscle, the reduction of which is a marker
of atrophy and is strongly correlated with its loss of strength and reference
measurements. In addition, ultrasound can be used to assess muscle quality, particularly
by evaluating the echogenicity of the muscle. Echogenicity increases with muscle damage,
related to the presence of fatty infiltrate and fibrous tissue. Complementary
measurements such as pennation angle, fascicular length or fibrillations allow to
complete the description of the muscle state.
Muscle ultrasonography is becoming increasingly used among the tools for assessing
muscle function, especially in sarcopenia found in many pathological situations. Its use
in the evaluation of the patient's nutritional status, as a tool for assessing muscle
function, is developing in the ICU and is associated with an increase in the patient's
comorbidities. Studies remain limited to a few patient populations, do not report clear
cut-off values to define muscle pathological status, and require more precise definition
of ultrasound measurement protocols.
1.6 Research hypothesis
The investigators hypothesize that muscle ultrasound is reliable and valid in the
evaluation of muscle function during the screening of undernutrition in a population of
hospitalized patients in diabetology-obesity, pneumology, oncology and gastro-nutrition,
under 70 years of age.
2. Objective 2.1 Main objective The main objective of this study is to evaluate the
reliability and validity of muscle ultrasound in the context of screening for
undernutrition in patients hospitalized in short-stay and follow-up care and
rehabilitation of diabetology-obesity, pneumology, oncology and gastro-nutrition.
2.2 Secondary objectives
The secondary objectives will be, in patients hospitalized in short stay and follow-up care
and rehabilitation of diabetes-obesity, pneumology, oncology and gastro-nutrition:
- Evaluate the correlation of muscle ultrasound with standard measures of muscle function;
- To compare the diagnostic capacity of muscle function assessment tools on
undernutrition;
3. Type of study: This is a prospective, monocentric, interventional cohort study. The
research will be conducted in accordance with the protocol. The duration of the
recruitment will be 20 months with a follow-up of the patients during their entire
hospitalization in the care unit, i.e. approximately 30 days (average length of stay),
i.e. a total duration of the study estimated at 21 months. The study will take place at
the Forcilles Hospital, in diabetology-obesity, pneumology, oncology and
gastro-nutrition units.
4. Description of the usual care 4.1 Usual course of treatment
Patients admitted to short-stay and follow-up care and rehabilitation for diabetes-obesity,
pneumology, oncology and gastro-nutrition benefit from medical, nursing and rehabilitation
examinations and care. All of this care will not be modified within the framework of this
protocol. Physiotherapists and dieticians provide their diagnostic assessment and
rehabilitation on medical prescription. The EAPAs participate in the functional evaluation of
the patient and carry out physical activities adapted to the patient, also on medical
prescription.
As part of the screening for undernutrition in our establishment, the dieticians ensure a
prospective and systematic collection of the patient's weight and its evolution over the last
few months, of his BMI and an evaluation of the food intake, within 48 hours of the patient's
admission to the service. The estimation of the patient's intake is done in collaboration
with the nursing assistant.
4.2 Nutritional assessment At the patient's admission, a dietetic evaluation is performed by
the dietician following the recommendations issued by the French Association of
Dieticians-Nutritionists and the HAS. The dietitian collects all the data needed to detect
malnutrition, such as weight, height, BMI, albumin level, and grip strength and walking speed
(performed by the caregiver and the physiotherapist or the EAPA). The dietician also looks
for possible obstacles to feeding such as dental condition, swallowing problems or digestive
discomfort The doctor looks for different pathologies impacting digestive absorption such as
shortened or shortened stool syndromes, gastrectomies, pancreatic insufficiency etc. He also
looks for factors of aggression such as cancers, chronic progressive diseases, infections
etc.
All these data allow us to estimate the theoretical nutritional needs of the patient and to
adapt the nutritional management. A follow-up of the ingestations is carried out by the
dietician in collaboration with the nurses' aides.
4.2.1 Anthropometric measurements When the patient is admitted, the ward's nurses and
orderlies measure the patient's weight and height. When the patient can maintain the erect
position, a conventional scale and a measuring rod are used for the measurements. If the
patient cannot maintain this position, a weighing chair and a laser meter are used.
In order to evaluate the weight loss before hospitalization, the previous weight is sought in
a hospitalization report or another recent medical document. A contact with the attending
physician is also made in order to obtain information concerning the patient's weight
follow-up. When this information is not available, the previous weight given by the patient
is collected.
4.2.2 Biological measurements On admission, a biological sample is usually taken from
patients at risk of undernutrition in order to measure pre-albumin, albumin and C-reactive
protein (CRP).
4.2.3 Measurements of muscle function Measurement of grip strength ("Handgrip") The gripping
force is evaluated with the Jamar® hydraulic force gauge by the caregiver. Measurement of the
walking speed ("Gait speed")
Walking speed (m/s) is measured on a 4-meter course, in a corridor, by the EAPA or the
physiotherapist.
5. Assessment procedure added by the research : Mini-Nutritional Assessment Short Version
(MNA-SF) score, Bioelectrical impedancemetry and muscle ultrasound.
6 Statistical aspects
6.1 Calculation of the number of subjects needed
Reproducibility of ultrasound With an expected intraclass correlation coefficient of at least
ρ1 = 0.8, a minimum value ρ0 = 0.70 considered acceptable, a number of observations k= 2, a
risk α= 0.05, and a power of 80%, it is necessary to include 118 patients for the study of
intra- and inter-examiner reproducibility of ultrasound.
Ultrasound Validity:
With an expected sensitivity and specificity of at least 90% and 85%, respectively, an
estimated prevalence of muscle impairment of 45% to 60% in our hospitalized patients, for a
risk α= 0.05 and a maximum width of the confidence interval of 10%, it is necessary to
include between 87 and 109 patients.
Therefore, it will be necessary to include 118 patients to meet the primary objective of
evaluating the validity and reliability of peripheral muscle ultrasound.
6.2 General aspects
Descriptive statistics will be based on means (+/- standard deviation) or medians
[interquartile range] depending on the distribution of quantitative variables. Qualitative
variables will be described in terms of numbers and percentages. Univariate comparisons will
use the usual statistical tests after verification of the distribution of the variables (Chi2
or Fisher's test, t-test, anova or their non-parametric equivalents Wilcoxon and
Kruskal-Wallis tests). Paired sample tests will be used if necessary.
Tests will be performed at the 5% significance level. The 95% confidence intervals will be
provided for each estimate.
The calculations will be done using SPSS v21 IBM and R software (version 3.6.1, http://www.R-
project.org ).
6.3 Morbidity and mortality criteria
6.3.1 Length of hospitalization The length of stay is defined as the number of days of
presence in the inclusion service, from the patient's admission to the final discharge.
Temporary transfers to another hospital department for an examination or an intervention are
not considered discharges.
A special statistical treatment will be carried out on the length of hospital stay, given the
impact of death on the length of stay.
6.3.2 Mortality Number of deaths out of the total number of patients included. A specific
statistical treatment will be performed on the mortality rate.
6.3.3 Katz Activities Daily Living (ADL) Score The Katz ADL score is completed within 48
hours prior to (scheduled) hospital discharge by the patient's caregiver or nurse. The total
score is out of 6. A score of less than 3 indicates major dependence, a score of 0 indicates
total dependence.
The Katz ADL score will be treated as a discrete numerical variable.
6.4 Analysis of the main objective
Inter- and intra-examiner reliability will be assessed by calculating intra-class correlation
coefficients.
Validity will be assessed by calculating the areas under the ROC curve (Receiver Operating
Characteristics) and calculating sensitivities, specificities, positive and negative
predictive values.
The reference test for the diagnosis of impaired muscle function is bioelectrical impedance.
The cut-off values used for the diagnosis of impaired muscle function are those recommended
by GLIM : Appendicular Skeletal Muscle Index (ASMI) < 7 kg/M2 in men and < 5.7 kg/m2 in
women.
6.5 Secondary objectives
6.5.1 Correlation of muscle ultrasound with standard measures of muscle function Measures of
association between quantitative variables will be performed using Pearson's or Spearman's
correlation coefficients depending on the distribution of the data. Measures of association
between qualitative variables will be performed using the Chi-square or Fisher test depending
on the distribution of the data.
The agreement between quantitative variables will be evaluated using the Bland-Altman method
and that between qualitative variables using the Kappa coefficient.
6.5.2 Compare the diagnostic capacity of muscle function assessment tools on undernutrition
The diagnostic capabilities of the different tools for measuring muscle function (Handgrip,
gait speed, bioelectrical impedance and muscle ultrasound) will be compared by ROC curves.
6.5.3 Evaluate the association of muscle ultrasound measurements with patient morbidity and
mortality Morbidity and mortality will be compared between the groups with and without
ultrasound-determined muscle function impairment, comparing length of hospital stay,
mortality, and independence at discharge.
Length of hospitalization There is a relationship between the incidence of mortality and all
of the length of stay variables. Length of stay will therefore be analyzed using a
competitive risk method, which takes into account the fact that patients who die are no
longer eligible for length of stay analysis.
The estimator also provides the probability of in-hospital death, so the probability of
hospital discharge versus death at any time after study inclusion can be assessed
simultaneously.
Mortality rate The estimation of mortality rates will be performed by the Kaplan and Meier
method. Comparison of the 2 curves will be performed by a Logrank test. The mortality rates
in the 2 groups will be estimated via the survival curves.
ADL The ADL score will be compared between the 2 groups using the discrete numerical variable
comparison tests described in the general aspects.
7. Expected results in terms of scientific and professional advances The results of this
study will make it possible to verify whether ultrasound is a reliable and valid tool in the
evaluation of peripheral muscle function in the context of screening for undernutrition. On
the other hand, they will allow us to propose threshold values for the alteration of muscle
function and to provide information on the ultrasound characteristics of the muscle in the
undernourished patient and their association with the prognosis of the patient. The different
tools could lead to a different estimation of the reduction of muscle mass and therefore a
different prevalence of undernutrition. The results of our study will help to evaluate this
and to guide professionals in the choice of tools to assess muscle function.
8 Expected benefits and risks for patients 8.1 Minimal risks and constraints added by the
research
All medical and paramedical examinations and management are usually performed except for the
MNA-SF questionnaire, muscle ultrasound and bioelectrical impedancemetry, which will be
performed systematically in the patients included. The MNA-SF questionnaire is very quick
(less than 5 minutes) and therefore causes very little inconvenience to the patient apart
from an additional visit by a caregiver. Bioelectrical impedancemetry is a tool for assessing
body composition using electrodes applied to the skin surface. The examination lasts an
average of 15 minutes and is non-invasive and painless. The minimal constraint is related to
the placement of the electrode and the duration of the examination. The ultrasound is also
non-invasive and painless. The 3 ultrasounds performed will last about 30m. The minimal
constraint is related to the installation of the ultrasound probe and the duration of the
examination.
8.2 Expected benefits for the patient
Ultrasound is a relatively simple and inexpensive tool compared to other methods of measuring
body composition (DEXA or MRI) and provides additional information on muscle quantity and
quality compared to the usual tools for measuring muscle function (Handgrip, functional
tests). The results of this study will make it possible to propose to the patient a reliable
and valid evaluation tool, more easily available and less restrictive in the evaluation of
the muscular quality during undernutrition. This could lead to a wider and more precise
evaluation of this muscular impairment in order to propose more adapted therapeutic solutions
(exercise training, weight training, nutrition).
