Clinical trial NCT04923165: Nutritional Status in Subacute Stroke Patients Under Rehabilitation
Official title: Influence of Nutritional Status on Rehabilitation Outcome in Subacute Stroke Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Stroke
Keywords: Stroke
Nutrition
Rehabilitation
Oxidative stress
Sarcopenia
Lead sponsor: Fondazione Don Carlo Gnocchi Onlus
Sponsor class: OTHER
First posted: 2021-06-11
Enrollment: 119
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with first ischemic stroke (of ischemic or hemorrhagic aetiology) in subacute phase (within six months after the acute event), hospitalized at the participating intensive-extensive rehabilitation centers will be included.

Brief summary: Recently, is becoming more evident a relationship between malnutrition, stroke-related sarcopenia and/or altered systemic oxidative status in patients with subacute stroke .

The aim of this study is the evaluation of nutritional status, the presence of stroke-related sarcopenia and systemic oxidative status in patients with subacute stroke outcomes; another aim is to investigate the correlation of nutritional status, the presence of stroke-related sarcopenia and systemic oxidative status on admission with the rehabilitative outcomes.

Detailed description: Stroke is the third leading cause of mortality and the second leading cause of permanent disability in adults, and is therefore very expensive. Some patients with stroke outcomes, regardless of baseline motor and cognitive function, for unknown reasons show an unexpectedly worse outcome than others and this suggests other factors, in addition to the degree of initial disability, that influence the response to rehabilitative treatment.

Nutrition is an essential aspect in the overall picture of the stroke patient. Malnutrition in the hospital setting is an important issue that can negatively influence the rehabilitation outcome (Cederholm et al. 2017; 2019).

Malnutrition is also responsible for the increase in complications, negatively affects the results of treatment, reduces the immune response and predisposes to infections, delays healing, compromises the function of organs and systems, reduces muscle mass and strength, induces psychic effects with depression and low interest in food.

All this leads to a demand for greater and more prolonged care, with a delay in the recovery of the performance (National Guidelines for hospital and care catering. Min. of Health, 2015).

A picture of malnutrition also leads to an alteration of biochemical and haematochemical indexes. Our retrospective pilot study on 30 patients with subacute stroke, showed a positive correlation between the reduction of disability following rehabilitation treatment and the calcium at admission (Siotto et al, 2020). In addition, a recent study with 100 patients admitted to a rehabilitation unit showed that the functional status at the time of admission and the improvement following the rehabilitation program were positively influenced by high blood levels of vitamin D (Lelli et al. 2019).

Malnourished patients experience "sarcopenia", which is characterized by the reduction of muscle mass and strength, and is a phenomenon strongly related to age: after the age of 70 years, in fact, there is a loss of 15% of muscle mass. It is a risk factor for falls, fractures, physical disability and mortality and it is a phenomenon dependent on various factors such as metabolic imbalance, inactivity, malnutrition and inflammatory states. Sarcopenia is accompanied by body weight loss, neuro-hormonal activation and a systemic shift towards catabolic over-activation (Knops et al. 2013).

Sarcopenia is frequently found in patients with stroke outcomes and can contribute negatively to the rehabilitation process. A recent study of 267 stroke patients admitted to a rehabilitation unit showed that those with sarcopenia (n=129 48%) had severe lower limb paralysis, lower Body Mass Index (BMI) values and a lower Functional Independence Measure (FIM) score, compared to patients without sarcopenia. In addition, patients with sarcopenia had a longer average stay with less chance of returning home and were less autonomous in walking. Finally, patients with sarcopenia showed a lower recovery of functional autonomy compared to non sarcopenic patients (Matsushita et al. 2019).

In stroke patients there is also "stroke-related sarcopenia" (Scherbakov, Sandek, and Doehner 2015) with distinctive features. The reasons are to be attributed to a complex of pathophysiological reactions including: altered neurovegetative control, alterations in the local and systemic metabolic system, difficulty in nutrition and inflammation (Scherbakov, Sandek, and Doehner 2015).

Some studies have led to hypothesize a correlation between sarcopenia and systemic oxidative stress. The general oxidative state is the result between levels of circulating oxidants (e.g. peroxides) and levels of endogenous or dietary acquired antioxidants (glutathione or vitamins, such as tocopherols, vitamin E, K). Our research team has recently demonstrated that circulating peroxides increase in stroke and are related to clinical severity (Squitti et al., 2018). The measurement of circulating peroxides evaluates the prooxidant state of a subject because it depends on circulating free radicals (Reactive Oxygen Species, ROS); these molecules have a great chemical reactivity, which, in extreme cases, compromises the function of all cellular macromolecules causing cell death; for this reason it is thought that sarcopenia may be at least partly due to an over-regulation of oxidative metabolism that produces high levels of circulating free radicals (Fulle et al. 2004).

The hypothesis of the study is that there is a negative relationship between malnutrition, stroke-related sarcopenia and/or altered systemic oxidative status in patients on admission and recovery following rehabilitative treatment.

therefore the aims of this study are:

* Evaluation of nutritional status, presence of stroke-related sarcopenia and systemic oxidative status in patients with subacute stroke outcomes;
* the correlation of nutritional status, the presence of stroke-related sarcopenia and systemic oxidative status on admission with the rehabilitative outcome.

Improving the nutritional picture of stroke patients from acute or post-acute wards will lead to a faster and more effective motor recovery and improve their autonomies and quality of life. This may lead to a lower impact of disability on families and caregivers and, more generally, a reduction in health care costs.

Longitudinal prospective multicentric, non-profit, longitudinal observational study conducted in patients with first stroke (ischemic or hemorrhagic) in subacute phase (within six months after the acute event). The study involves the collection of clinical, instrumental and biochemical data that do not deviate from routine clinical practice. Since it is not an experimental study, no specific intervention is planned; patients will be observed before and after the usual rehabilitative intervention.

The study will have a total duration of 18 months starting in January 2021 and a patient enrolment time of 1 year.

Eligibility criteria: Inclusion Criteria:

* stroke patients (hemorrhagic or ischemic) documented through Magnetic Resonance Imaging (MRI) or Computed Tomography (CT);
* age between 18 and 85 years;
* latency time within 6 months after the stroke event
* sufficient cognitive and language skills to understand the instructions related to the administration of the assessment scales and to sign informed consent

Exclusion Criteria:

* presence of a previous stroke based on the medical history;
* behavioral and cognitive disorders that may interfere with the therapeutic activity;
* other orthopedic or neurological complications that may interfere with the rehabilitation protocol;
* inability to understand and sign informed consent;
* presence of pacemakers (for interference with bioimpedance measures).

Primary outcomes:
measure: change in Mini nutritional Assessment (MNA) scores
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in Body Mass Index
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: weight change
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in food income detection
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in Bioimpedance analysis (BIA) measurements
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in hand grip strenght test score
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in Time Up & Go test (TUG) scores
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in Barthel index (BI) scores
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in Fugl-Meyer Assessment of Motor Recovery after Stroke for Upper Extremity portion (FMA-UL) scores
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in Motricity Index (MI) scores
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in Numerical Rating Scale (NRS) scores
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in Neuropathic Pain Four Questions (DN4) scores
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in Modified Ashworth Scale (MAS) scores
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in 10 Meter Walk Test scores
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in Six-Minute Walking Test (6MWT) scores
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in blood levels of systemic oxidative stress (dROMs)
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in antioxydant capacity of serum (BAP)
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in thiol serum levels (SHp)
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change haemoglobin serum levels
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in glucose serum levels
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in albumine serum levels
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in triglycerides serum levels
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in total cholesterol serum levels
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in HDL cholesterol serum levels
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in calcium serum levels
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in magnesium serum levels
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in creatinin serum levels
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in iron serum levels
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in latent iron binding capacity serum levels
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
measure: change in hepatic status serum levels (ALT-GPT)
timeFrame: Baseline (T0), Treatment (6 weeks) (T1)
Secondary outcomes:
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Don Gnocchi Foundation
Study officials:
affiliation: IRCCS Fondazione Don Carlo Gnocchi
name: Irene APRILE, MD,PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cederholm T, Barazzoni R, Austin P, Ballmer P, Biolo G, Bischoff SC, Compher C, Correia I, Higashiguchi T, Holst M, Jensen GL, Malone A, Muscaritoli M, Nyulasi I, Pirlich M, Rothenberg E, Schindler K, Schneider SM, de van der Schueren MA, Sieber C, Valentini L, Yu JC, Van Gossum A, Singer P. ESPEN guidelines on definitions and terminology of clinical nutrition. Clin Nutr. 2017 Feb;36(1):49-64. doi: 10.1016/j.clnu.2016.09.004. Epub 2016 Sep 14.
citation: Cederholm T, Jensen GL, Correia MITD, Gonzalez MC, Fukushima R, Higashiguchi T, Baptista G, Barazzoni R, Blaauw R, Coats A, Crivelli A, Evans DC, Gramlich L, Fuchs-Tarlovsky V, Keller H, Llido L, Malone A, Mogensen KM, Morley JE, Muscaritoli M, Nyulasi I, Pirlich M, Pisprasert V, de van der Schueren MAE, Siltharm S, Singer P, Tappenden K, Velasco N, Waitzberg D, Yamwong P, Yu J, Van Gossum A, Compher C; GLIM Core Leadership Committee; GLIM Working Group. GLIM criteria for the diagnosis of malnutrition - A consensus report from the global clinical nutrition community. Clin Nutr. 2019 Feb;38(1):1-9. doi: 10.1016/j.clnu.2018.08.002. Epub 2018 Sep 3.
citation: Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, Martin FC, Michel JP, Rolland Y, Schneider SM, Topinkova E, Vandewoude M, Zamboni M; European Working Group on Sarcopenia in Older People. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing. 2010 Jul;39(4):412-23. doi: 10.1093/ageing/afq034. Epub 2010 Apr 13.
citation: Fulle S, Protasi F, Di Tano G, Pietrangelo T, Beltramin A, Boncompagni S, Vecchiet L, Fano G. The contribution of reactive oxygen species to sarcopenia and muscle ageing. Exp Gerontol. 2004 Jan;39(1):17-24. doi: 10.1016/j.exger.2003.09.012.
citation: Knops M, Werner CG, Scherbakov N, Fiebach J, Dreier JP, Meisel A, Heuschmann PU, Jungehulsing GJ, von Haehling S, Dirnagl U, Anker SD, Doehner W. Investigation of changes in body composition, metabolic profile and skeletal muscle functional capacity in ischemic stroke patients: the rationale and design of the Body Size in Stroke Study (BoSSS). J Cachexia Sarcopenia Muscle. 2013 Sep;4(3):199-207. doi: 10.1007/s13539-013-0103-0. Epub 2013 Mar 13.
citation: Lelli D, Perez Bazan LM, Calle Egusquiza A, Onder G, Morandi A, Ortolani E, Mesas Cervilla M, Pedone C, Inzitari M. 25(OH) vitamin D and functional outcomes in older adults admitted to rehabilitation units: the safari study. Osteoporos Int. 2019 Apr;30(4):887-895. doi: 10.1007/s00198-019-04845-7. Epub 2019 Jan 16.
citation: Scherbakov N, Sandek A, Doehner W. Stroke-related sarcopenia: specific characteristics. J Am Med Dir Assoc. 2015 Apr;16(4):272-6. doi: 10.1016/j.jamda.2014.12.007. Epub 2015 Feb 10.
citation: Squitti R, Siotto M, Assenza G, Giannantoni NM, Rongioletti M, Zappasodi F, Tecchio F. Prognostic Value of Serum Copper for Post-Stroke Clinical Recovery: A Pilot Study. Front Neurol. 2018 May 30;9:333. doi: 10.3389/fneur.2018.00333. eCollection 2018.
citation: Matsushita T, Nishioka S, Taguchi S, Yamanouchi A. Sarcopenia as a predictor of activities of daily living capability in stroke patients undergoing rehabilitation. Geriatr Gerontol Int. 2019 Nov;19(11):1124-1128. doi: 10.1111/ggi.13780. Epub 2019 Oct 7.
citation: Siotto, M., Germanotta, M., Santoro, M., Di Blasi, C., Loreti, C., Mastropaolo, S. & Aprile, I.,Total serum calcium and recovery after rehabilitation in patients with stroke Nov 1 2020, In : Applied Sciences (Switzerland). 10, 21, p. 1-8 8 p., 7893.
citation: Santoro M, Siotto M, Germanotta M, Bray E, Mastrorosa A, Galli C, Papadopoulou D, Aprile I. BDNF rs6265 Polymorphism and Its Methylation in Patients with Stroke Undergoing Rehabilitation. Int J Mol Sci. 2020 Nov 10;21(22):8438. doi: 10.3390/ijms21228438.