Clinical trial NCT02125760: Respiratory Muscle Training in Subacute Stroke Patients
Official title: The RETORNUS Study: Dual Training to Restore the Function of Respiratory Muscles in Stroke Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Muscle Weakness
Keywords: Respiratory muscle training
stroke
rehabilitation
Lead sponsor: Parc de Salut Mar
Sponsor class: OTHER
First posted: 2014-04-29
Enrollment: 129
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is divided for development in two complementary work packages justified by the need to incorporate new strategies to optimize rehabilitation outcomes in stroke patients. The general objectives are: 1) to determine the prevalence of respiratory muscle dysfunction in stroke patients; 2) to identify the existence of a potential amino acid marker of increased risk of muscle dysfunction after suffering a stroke; 3) to evaluate the effectiveness of incorporating the respiratory muscle training as an innovative adjuvant therapy in stroke rehabilitation program that may decrease the incidence of morbidity and mortality in the medium and long term; and 4) to quantify the potential impact of respiratory muscle training on the costs of care for stroke patients.

Detailed description: Stroke is a major cause of morbidity and mortality worldwide. It determines a substantial socioeconomic burden. Stroke can lead to varying degrees of oropharyngeal dysphagia (25-85% of patients) and respiratory muscle dysfunction associated with an increase in medical complications such as bronchoaspiration pneumonia, malnutrition and death. The respiratory muscle dysfunction is a common functional abnormality in chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD), heart failure, multiple sclerosis in which it has been shown to modify the expected survival. Dysphagia is present in a significant proportion of patients admitted to Rehabilitation (up to 85% depending on series) in the subacute phase of stroke. There is no drug able to restore the swallowing function and inspiratory and expiratory muscle function in these patients. Consequently, neurological rehabilitation is the mainstay of treatment of these disorders.

Amino acids (AA) are essential for proper protein synthesis. Skeletal muscle represents the largest reserve of body AA, which may be used according to metabolic needs. Within this group of compounds, the most involved in muscle metabolism are glutamate, aspartate, asparagine, valine, leucine and isoleucine. A pathobiological association between decrease in muscle glutamate and diaphragm dysfunction in patients with chronic respiratory diseases has been demonstrated in chronic respiratory patients. Moreover, glutamate levels of the diaphragm can be restored as a result of muscle training, playing a decisive role as a precursor of certain AA (glutamine and alanine), and glutathione in patients with COPD. Other studies have defined that glutamine may be a biomarker of training response in healthy individuals. Several publications have reflected the decrease of glutamine and glutamate as a result of different diseases and in some cases have tried to supplement this deficit.

Muscle dysfunction is defined as a function impairment (decrease in strength and/or resistance) of muscles whose main consequence is muscle fatigue. Although exercise training has been used successfully to restore function in patients with some chronic illnesses and frailty, there is little evidence of the beneficial effects of an overall muscle training in stroke patients. Regarding peripheral muscles, a high-intensity training improves strength and endurance of lower limbs muscles (paretic and non paretic) in stroke patients. Dysfunction of the diaphragm and other respiratory muscles has important clinical implications. It associates with susceptibility to hypercapnic ventilatory failure, ineffective cough, and even higher incidence of repeated hospital admissions and mortality. Therefore, respiratory muscle weakness described in some stroke patients justifies the need to train respiratory muscles because there is no general exercise (bicycle, legs, arms) able to induce an overload enough to achieve training effect on respiratory muscles.

Eligibility criteria: Inclusion Criteria:

* Hemiplegia secondary to first ischemic stroke in the subacute phase, and
* informed consent signed by the candidates of the study, after receiving full information on objectives, techniques and possible consequences.

Exclusion Criteria:

* Serious cardiovascular, neuromuscular or metabolic conditions that could interfere with the results and/or interfere with the measurements,
* significant alcohol abuse (\> 80 g/day) or severe malnutrition, and
* treatment with drugs with potential effect on muscle structure and function (steroids, anabolic steroids, thyroid hormones and immunosuppressants).

Primary outcomes:
measure: Respiratory muscle strength
timeFrame: 3 weeks
Secondary outcomes:
measure: Handgrip strength assessment
timeFrame: 3 weeks
measure: Lower limb strength measurement
timeFrame: 3 weeks
measure: Serum aminoacids analysis
timeFrame: Up to 3 weeks
measure: Adverse events as a measure of safety and tolerability
timeFrame: 18 months after discharge
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Physical Medicine and Rehabilitation Dpt. Parc de Salut Mar, Hospital del Mar
Study officials:
affiliation: Institut Hospital del Mar d'Investigacions Mèdiques. Universitat Autònoma de Barcelona.
name: Esther Duarte, MD, PhD
role: STUDY_DIRECTOR
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