Respiratory Muscle Training in Subacute Stroke Patients (RETORNUS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Parc de Salut Mar
Sponsor:
Information provided by (Responsible Party):
Parc de Salut Mar
ClinicalTrials.gov Identifier:
NCT02125760
First received: April 23, 2014
Last updated: April 25, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention
Muscle Weakness
Other: Inspiratory Muscle Training (IMT)
Other: High-intensity IMT

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: The RETORNUS Study: Dual Training to Restore the Function of Respiratory Muscles in Stroke Patients

Resource links provided by NLM:


Further study details as provided by Parc de Salut Mar:

Primary Outcome Measures:
  • Respiratory muscle strength [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]

    Respiratory muscle strength is assessed through maximal inspiratory and expiratory pressures (MIP and MEP, respectively) using a pressure transducer connected to a digital register system. The MIP is measured at mouth during a maximum effort from residual volume against occluded airway. To determine the MEP, the patients will perform a maximum expiratory effort from total lung capacity (TLC) in the face of the occluded airway. A specific and validated respiratory pressures manometer will be used (Micro RPM, Cardinalhealth, Kent, UK). For the purposes of the study, 'responders' will include the group of patients with an increase of 25% or more in respiratory muscle strength (MIP and MEP).

    Measures will be done once every week



Secondary Outcome Measures:
  • Handgrip strength assessment [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]

    Handgrip strength will be assessed during maximal voluntary isometric contraction of the flexor muscles of the fingers, using a dynamometer (JAMAR, Nottinghamshire, UK). We consider both the non-dominant and dominant hand. Reference values are those from Webb et al. (J Par Ent Nutr 1989, 13:30-3).

    Measures once every week


  • Lower limb strength measurement [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]

    Lower limb strength will be measured during a maximal voluntary isometric knee extension while the patient is sit in a bank of exercise (DOMYOS HG 050, Decathlon, France). An isometric dynamometer Nicholas Manual Muscle Tester (NMMT) (Lafayette Instrument Company, Lafayette, Indiana) will be used according to Dunn JC (J Phys Ther Ger 2003).

    Measures once every week


  • Serum aminoacids analysis [ Time Frame: Up to 3 weeks ] [ Designated as safety issue: No ]
    Analysis of plasma samples (high performance liquid chromatography (HPLC) will determine levels of glutamine, valine, isoleucine, leucine and glutamate at baseline and at the end of muscle training using the technique previously described and validated (Clin Chem 1988, 34 (12): 2510-3). Venous blood samples will be collected in heparinized tube and centrifuged to obtain plasma. Later proceed to deproteinization with sulfosalicylic acid for analyzing the concentration of amino acids (AA). Finally the sample will be frozen at -80 º C for further analysis.

  • Adverse events as a measure of safety and tolerability [ Time Frame: 18 months after discharge ] [ Designated as safety issue: Yes ]
    Comorbidity variables (occurrence of complications, hospital admissions, hospital length of stay) and mortality.


Estimated Enrollment: 129
Study Start Date: March 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Sham Comparator: Inspiratory Muscle Training (IMT)
Patients with subacute stroke in a neurorehabilitation setting.
Other: Inspiratory Muscle Training (IMT)
Sham IMT at a fixed workload of 10 cmH2O. 5 sets of 10 repetitions, twice a day, 7 days per week, for 4 weeks.
Other Name: No applicable
Experimental: High-intensity IMT
Patients with subacute stroke in a neurorehabilitation setting.
Other: High-intensity IMT
High Intensity IMT. The training load is the maximum inspiratory load defined according to patient tolerance. This load will be equivalent to 10 maximal repetitions (RM) as 10 consecutive inspirations (x 5 sessions), twice a day.
Other Name: Short duration respiratory muscle training

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02125760

Contacts
Contact: Ester Marco, MD, PhD +34 933674214 emarco@hospitaldelmar.cat
Contact: Esther Duarte, MD, PhD +34 933674214 eduarte@parcdesalutmar.cat

Locations
Spain
Physical Medicine and Rehabilitation Dpt. Parc de Salut Mar, Hospital del Mar Recruiting
Barcelona, Spain, 08003
Contact: Ester Marco, MD, PhD    +34 933674214    emarco@hospitaldelmar.cat   
Contact: Ester Duarte, MD, PhD    +34 933674214    eduarte@parcdesalutmar.cat   
Principal Investigator: Ester Marco, MD, PhD         
Sub-Investigator: Monique Sartor         
Sub-Investigator: Anna Guillén-Solà, MD         
Sub-Investigator: Marina Depolo, MD         
Sub-Investigator: Diego A Rodríguez, MD, PhD         
Sub-Investigator: Mauricio Orozco-Levi, MD, PhD         
Sponsors and Collaborators
Parc de Salut Mar
Investigators
Study Director: Esther Duarte, MD, PhD Institut Hospital del Mar d'Investigacions Mèdiques. Universitat Autònoma de Barcelona.
  More Information

Publications:

Responsible Party: Parc de Salut Mar
ClinicalTrials.gov Identifier: NCT02125760     History of Changes
Other Study ID Numbers: PSM/RHB/NR/14, RETORNUS
Study First Received: April 23, 2014
Last Updated: April 25, 2014
Health Authority: Spain: Comité Ético de Investigación Clínica

Keywords provided by Parc de Salut Mar:
Respiratory muscle training
stroke
rehabilitation

Additional relevant MeSH terms:
Muscle Weakness
Paresis
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Pathologic Processes
Signs and Symptoms

ClinicalTrials.gov processed this record on September 18, 2014