Physical Fitness Training in Subacute Stroke (PHYS-Stroke)

The aim of this study is to investigate whether a 4-week physical fitness training (target intervention) in stroke patients (subacute stage) increase the walking speed and activities of daily living compared with a control intervention (relaxation exercises). The target or control intervention is performed in addition to standard rehabilitation treatment.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Procedure: physical fitness training; Procedure: relaxation

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 12351
    • Vivantes Klinikum Neukölln
  • Berlin, Germany, 10117
    • Charité - Universitätsmedizin Berlin
  • Berlin, Germany, 12200
    • Charite Campus Benjamin Franklin
  • Berlin, Germany, 13347
    • Evanglisches Geriatriezentrum Berlin
  • Berlin, Germany, 13507
    • Medical Park Berlin
  • Brandenburg
    • Beelitz Heilstatten, Brandenburg, Germany, 14547
      • Beelitz Heilstätten
    • Grunheide, Brandenburg, Germany, 15537
      • Median Klinik Grünheide

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria for patients:

• diagnosis of stroke within 5-45 days after stroke
• age >= 18 years
• able to sit for at least 30 seconds
• Barthel index < =65 at inclusion
• considered able to perform aerobic exercise as determined by responsible physician
• Written informed consent of the patient

Exclusion Criteria:

• Patient considered unable to comply with study requirements
• stroke due to intracranial hemorrhage primarily due to bleeding from ruptured aneurysm or arteriovenous malformation
• patients with progressive stroke

• unable to perfom the required exercises due to

  1. medical problems
  2. musculo-skeletal problems
  3. neurological problems
• required help to at least 1 persons to walk before stroke due to neurological or non-neurological co-morbidities
• life expectancy of less than 1 year as determined by responsible physician
• alcohol or drug addiction within the last 6 months
• significant current psychiatric illness as defined as medication-refractory of bipolar affective disorder, psychosis, schizophrenia or suicidality
• current participation in another intervention study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: physical fitness training; aerobic physical fitness training	Procedure: physical fitness training
Active Comparator: relaxation; non-aerobic training	Procedure: relaxation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gait speed and Barthel Index (BI) (co-primary endpoint)	comparing gait speed (m/s) and points achieved in BARTHEL Index in aerobic and non-aroebic training group 3 months after stroke vs baseline (before intervention)	3 months post stroke vs baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gait speed and Barthel Index (BI)	comparing gait speed (m/s) and points achieved in BI in aerobic and non-aroebic training group after the 4-week intervention interval as well as after 6 months post stroke vs baseline (before intervention)	directly after intervention; 6 months post stroke; all vs baseline
motor function	comparing motor function (assessed via different clinical scales e.g. Rivermead Arm test, REPAS, Box and Block Test, Medical Research Council Scale) in aerobic and non-aroebic training group after the 4-week intervention interval as well as after 3 and after 6 months post stroke vs baseline (before intervention)	directly after intervention; 3 months post stroke; 6 months post stroke; all vs baseline
mobility	comparing different mobilitiy indices like gait endurance (in min), stride length, step cadence, use of walking aids, actigraph measurements and the Rivermead mobility Index in aerobic and non-aroebic training group after the 4-week intervention interval as well as after 3 and after 6 months post stroke vs baseline (before intervention)	directly after intervention; 3 months post stroke; 6 months post stroke; all vs baseline
cognitive function	comparing cognitive function (assessed via points achieved in different scales, e.g. Montreal Cognitive Assessment, Trail Making test, word fluency) in aerobic and non-aroebic training group after the 4-week intervention interval as well as after 3 and after 6 months post stroke vs baseline (before intervention)	directly after intervention; 3 months post stroke; 6 months post stroke; all vs baseline
Disability	comparing disability (Modified rankin scale) in aerobic and non-aroebic training group after the 4-week intervention interval as well as after 3 and after 6 months post stroke vs baseline (before intervention)	directly after intervention; 3 months post stroke; 6 months post stroke; all vs baseline
Quality of life (QoL)	comparing QoL (EQ-5D-5L scale) in aerobic and non-aroebic training group after the 4-week intervention interval as well as after 3 and after 6 months post stroke vs baseline (before intervention)	directly after intervention; 3 months post stroke; 6 months post stroke; all vs baseline
sleep	comparing sleep quality (Pittsburgh sleep quality index) in aerobic and non-aroebic training group after the 4-week intervention interval as well as after 3 and after 6 months post stroke vs baseline (before intervention)	directly after intervention; 3 months post stroke; 6 months post stroke; all vs baseline
mood	comparing mood (CES-D scale) in aerobic and non-aroebic training group after the 4-week intervention interval as well as after 3 and after 6 months post stroke vs baseline (before intervention)	directly after intervention; 3 months post stroke; 6 months post stroke; all vs baseline
Physical fitness	comparing gait energy Expenditure in aerobic and non-aroebic training group after the 4-week intervention interval as well as after 3 and after 6 months post stroke vs baseline (before intervention)	directly after intervention; 3 months post stroke; 6 months post stroke, all vs baseline
Assessment of safety	comparing different criteria (recurrent fatal or non-fatal cardiovascular or cerebrovascular events, refferal to acute hospital, death) in aerobic and non-aroebic training group after the 4-week intervention interval as well as after 3 and after 6 months post stroke vs baseline (before intervention)	directly after intervention; 3 months post stroke; 6 months post stroke; all vs baseline
Maximal walking speed and Barthel-Index	per Protocol analysis of co-primary endpoint (pre-specified in statistical analysis plan and protocol)	3 months post stroke vs. baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
resting systolic and diastolic blood pressure	comparing resting systolic and diastolic blood pressure (mmHg) in aerobic and non-aroebic training group after the 4-week intervention interval as well as after 3 and after 6 months post stroke vs baseline (before intervention); part of substudy 'Biomarkers and Perfusion - Training-Induced Changes After Stroke (BAPTISe)' - NCT01954797 (will be analyzed seperately)	directly after intervention; 3 months post stroke; 6 months post stroke, all vs baseline
laboratory parameters	comparing different laboratory parameters (derived by blood draw) like hormones, hemogram, liver and kidney function, and coagulation parameters in aerobic and non-aroebic training group after the 4-week intervention interval as well as after 3 and after 6 months post stroke vs baseline (before intervention); part of substudy 'Biomarkers and Perfusion - Training-Induced Changes After Stroke (BAPTISe)' - NCT01954797 (will be analyzed seperately)	directly after intervention; 3 months post stroke; 6 months post stroke; all vs baseline
hair cortisol concentration	hair cortisol concentration by taking a small strand of hair is measured at baseline; part of substudy 'Biomarkers and Perfusion - Training-Induced Changes After Stroke (BAPTISe)' - NCT01954797 (will be analyzed seperately)	at baseline
resting heart rate	comaparing resting heart rate(beats/minute) in aerobic and non-aroebic training group after the 4-week intervention interval as well as after 3 and after 6 months post stroke vs baseline (before intervention); part of substudy 'Biomarkers and Perfusion - Training-Induced Changes After Stroke (BAPTISe)' - NCT01954797 (will be analyzed seperately)	directly after intervention; 3 months post stroke; 6 months post stroke; all vs baseline
waist to hip ratio	comparing waist to hip ratio (cm) in aerobic and non-aroebic training group after the 4-week intervention interval as well as after 3 and after 6 months post stroke vs baseline (before intervention); part of substudy 'Biomarkers and Perfusion - Training-Induced Changes After Stroke (BAPTISe)' - NCT01954797 (will be analyzed seperately)	directly after intervention; 3 months post stroke; 6 months post stroke; all vs baseline
markers of peripheral immunity	comapring markers of peripheral immunity (e.g., monocytic HLA-DR expression) in aerobic and non-aroebic training group after the 4-week intervention interval as well as after 3 and after 6 months post stroke vs baseline (before intervention); part of substudy 'Biomarkers and Perfusion - Training-Induced Changes After Stroke (BAPTISe)' - NCT01954797 (will be analyzed seperately)	directly after intervention; 3 months post stroke; 6 months post stroke; all vs baseline
lipid profile	comparing lipide such as triglycerides, cholesterol (total, LDL,HDL, and LP(a)) in aerobic and non-aroebic training group after the 4-week intervention interval as well as after 3 and after 6 months post stroke vs baseline (before intervention); part of substudy 'Biomarkers and Perfusion - Training-Induced Changes After Stroke (BAPTISe)' - NCT01954797 (will be analyzed seperately)	directly after intervention; 3 months post stroke; 6 months post stroke; all vs baseline
blood glucose	comparing insulin, glucose, and HbA1c in aerobic and non-aroebic training group after the 4-week intervention interval as well as after 3 and after 6 months post stroke vs baseline (before intervention); part of substudy 'Biomarkers and Perfusion - Training-Induced Changes After Stroke (BAPTISe)' - NCT01954797 (will be analyzed seperately)	directly after intervention; 3 months post stroke; 6 months post stroke; all vs baseline
markers of inflammation	comparing markers of inflammation (e.g., including Interleukin (IL) 6, 1b, hs-CRP) in aerobic and non-aroebic training group after the 4-week intervention interval as well as after 3 and after 6 months post stroke vs baseline (before intervention); part of substudy 'Biomarkers and Perfusion - Training-Induced Changes After Stroke (BAPTISe)' - NCT01954797 (will be analyzed seperately)	directly after intervention; 3 months post stroke; 6 months post stroke; all vs baseline
body mass index	comparing body mass index in aerobic and non-aroebic training group after the 4-week intervention interval as well as after 3 and after 6 months post stroke vs baseline (before intervention); part of substudy 'Biomarkers and Perfusion - Training-Induced Changes After Stroke (BAPTISe)' - NCT01954797 (will be analyzed seperately)	directly after intervention; 3 months post stroke; 6 months post stroke; all vs baseline
Endothelial function	the endothelial function of included patients will be assessed prospectively before and after the 4 week intervention with the Endopat2000 device. First measurement was conducted in January 11th 2014. Results will be correlated with imaging and blood-derived biomarkers as well as differences between intervention groups; part of substudy 'Biomarkers and Perfusion - Training-Induced Changes After Stroke (BAPTISe)' - NCT01954797 (will be analyzed seperately)	directly after intervention vs. baseline
Magnetic resonance imaging parameters	Primary and secondary endpoints are specified after completion of the interim analysis after inclusion of the first 24 patients (first stage). In a second stage the study is conducted with specified primary and secondary endpoints with recruitment of up to 76 remaining patients; part of substudy 'Biomarkers and Perfusion - Training-Induced Changes After Stroke (BAPTISe)' - NCT01954797 (will be analyzed seperately)	directly after intervention vs. baseline

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany

Publications and helpful links

General Publications

• Floel A, Werner C, Grittner U, Hesse S, Jobges M, Knauss J, Seifert M, Steinhagen-Thiessen E, Govercin M, Dohle C, Fischer W, Schlieder R, Nave AH, Meisel A, Ebinger M, Wellwood I. Physical fitness training in Subacute Stroke (PHYS-STROKE)--study protocol for a randomised controlled trial. Trials. 2014 Feb 3;15:45. doi: 10.1186/1745-6215-15-45.
• Kirzinger B, Stroux A, Rackoll T, Endres M, Floel A, Ebinger M, Nave AH. Elevated Serum Inflammatory Markers in Subacute Stroke Are Associated With Clinical Outcome but Not Modified by Aerobic Fitness Training: Results of the Randomized Controlled PHYS-STROKE Trial. Front Neurol. 2021 Aug 26;12:713018. doi: 10.3389/fneur.2021.713018. eCollection 2021.
• Nave AH, Rackoll T, Grittner U, Blasing H, Gorsler A, Nabavi DG, Audebert HJ, Klostermann F, Muller-Werdan U, Steinhagen-Thiessen E, Meisel A, Endres M, Hesse S, Ebinger M, Floel A. Physical Fitness Training in Patients with Subacute Stroke (PHYS-STROKE): multicentre, randomised controlled, endpoint blinded trial. BMJ. 2019 Sep 18;366:l5101. doi: 10.1136/bmj.l5101.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): July 6, 2017
• Study Completion (Actual): November 1, 2017

Study Registration Dates

• First Submitted: June 28, 2013
• First Submitted That Met QC Criteria: September 26, 2013
• First Posted (Estimate): October 1, 2013

Study Record Updates

• Last Update Posted (Actual): June 6, 2019
• Last Update Submitted That Met QC Criteria: June 4, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: physical activity, relaxation, activities of daily living, motor functions, cognitive functions
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: PHYS-Stroke

Plan for Individual participant data (IPD)

Study Data/Documents

1. Statistical Analysis Plan
   Information comments: Statistical Analysis Plan of PHYS-Stroke Trial. If download path is offline please contact torsten.rackoll@charite.de