Muscle Wasting in the Critically Ill

NCT ID: NCT03770442

Last Updated: 2020-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-14
• Study Completion Date: 2020-11-01

Brief Summary

Muscle wasting is a common consequence of critical illness, and has a profound impact upon the rehabilitation of those who survive admission to critical to care. The investigators intend to assess if the application of 10 sessions over two weeks of passive cycling with electrical stimulation to the lower limbs and abdomen can prevent muscle loss, or at least cause less muscle loss, compared to patients who receive standard daily sessions of physiotherapy. This will be done by comparing the changes in muscle size on ultrasound between the two groups, comparing functional measures at a 3 month follow up, and by performing translational research using tissue samples taken during the study.

Detailed Description

Patients are mechanically ventilated and sedated with a diagnosis of sepsis (from any source) will be eligible for this study. Provided they meet the inclusion criteria, they will be randomised within 48 hours of admission, to either ten 30 minute sessions of passive cycling with functional electrical stimulation (FES) to the thighs, hamstrings, calves and abdomen over a 14 day period, or to a control group of routine physiotherapy. The trial group will also receive this physiotherapy.

On admission to the study, all patients will receive on day 1:

Ultrasound measurements of:

Rectus femoris cross-sectional area Thickness of rectus femoris and vastus intermedius Thickness, pennation angle and derived fascicle length of vastus lateralis and medial head of gastrocnemius Thickness of rectus abdominis. Thickness of diaphragm

A blood sample taken from an arterial line A urine sample taken from a urinary catheter A muscle biopsy taken from the right vastus lateralis

They will then receive ten 30 minute sessions of passive cycling with functional electrical stimulation over 14 days, or a control group will receive routine physiotherapy during this period.

Repeat ultrasounds will be taken at days 3, 5, 7, 10 and 14. Repeat blood and urine sampling at days 5, 10 and 14. Repeat muscle biopsy at day 14.

All cycling, ultrasounds and tissue sampling will end on day 14 regardless of the ventilator status of the patient.

In patients who survive to be discharged from critical care, they will be followed up at 3 months for:

Repeat ultrasound scan of all muscles listed Six minute walk test Hand grip and lower limb dynamometry, Balance testing (by standing upright on a pressure plate for 20 seconds) Psychological assessment using the 36 item Short Form (SF-36) questionnaire

Tissue sampling will be stored in the University of Liverpool for analysis of biomarkers of muscle damage and loss between the two groups.

Conditions

Muscle Weakness

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Cycling with FES

Ten sessions of 14 days in patients consented within 48 hours of arriving in critical care who are sedated and mechanically ventilated with a diagnosis of sepsis from any source.

Sessions last a maximum of 30 minutes (with an ideal minimum of 20 minutes), using the Restorative Therapies (RT) 300 Supine with the Sage 12-channel stimulator. Stimulation will provided to the quadriceps, hamstrings, calves and abdomen. Both legs and both sides of the abdomen will be stimulated. Stimulation current settings are individualised for each patient and each muscle group.

These patients will also receive their routine physiotherapy that they would have received if they were in the control group (or not in the trial at all).

Group Type: EXPERIMENTAL

Cycling with FES

Intervention Type: DEVICE

As described already

Control - routine physiotherapy

Usual daily physiotherapy, consisting of limb care and mobilisation, and respiratory care and exercises as appropriate.

Group Type: ACTIVE_COMPARATOR

Routine physiotherapy

Intervention Type: OTHER

As described already

Interventions

Cycling with FES

As described already

Intervention Type: DEVICE

Routine physiotherapy

As described already

Intervention Type: OTHER

Other Intervention Names

RT-300 Supine; Restorative Therapies

Eligibility Criteria

Inclusion Criteria

• Patients will be recruited in the Intensive Care Unit of the Royal Liverpool University Hospital. All patients will be over 18, and have a critical illness that requires mechanical ventilation with an initial period of sedation. This study will focus on patients with a definite or suspected case of sepsis from any source.

Sepsis has been recently redefined as: "Life threatening organ-dysfunction caused by dysregulated host response to infection" whilst septic shock has become a subset of sepsis, defined as: "circulatory and cellular/metabolic dysfunction associated with a higher risk of mortality(44).

For the purposes of this study, a patient will be regarded as septic if they have evidence of infection-related organ failure (e.g. sepsis-associated coagulopathy, altered mental state, cardiovascular dysfunction, acute kidney injury, and altered liver function) and require invasive mechanical ventilation with either definite or suspected evidence of infection. This is to allow prompt treatment with FES rather than waiting for a positive microbiological result to be obtained.

Within the definition of sepsis "from any source" a list of following is illustrative but not exhaustive:

• Urogenital sepsis (including urosepsis, pyelonephritis, endometritis and chorioamnionitis)
• Pneumonia (including community acquired, hospital acquired, and aspiration pneumonia. Ventilator associated pneumonia would be excluded.)
• Neurological infections such as encephalitis and meningitis.
• Cellulitis, osteomyelitis and infections of soft tissue NOT affecting the lower limb.
• Surgical infections, including post-operative laparotomy with evidence of peritoneal soiling, and evidence of infection prior to the operation, in patients who require 2 or more organ system support after the operation.
• Intra-abdominal sepsis, including biliary sepsis, hepatitis, and acute pancreatitis. In the case of acute pancreatitis, evidence of infection is required to fulfil the criteria. Acute pancreatitis with sterile tissue/fluid samples would not be suitable.

Exclusion Criteria

• Patients under 18
• Patients who decline consent
• Pregnancy
• Neuromuscular disease
• Rhabdomyolysis
• Lower limb trauma
• Patients unlikely to survive to 96 hours post admission
• Consent unobtainable within 48 hours of admission
• Morbid obesity (BMI>40).
• Presence of a pacemaker or Implantable Cardiac Defibrillator (ICD).
• Unlikely to be mechanically ventilated for more than 48 hours.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Liverpool

OTHER

Sponsor Role: lead

Responsible Party

Ingeborg Welters

Senior Lecturer, Institute of Aging and Chronic Disease

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ingeborg D Welters

Role: PRINCIPAL_INVESTIGATOR

University of Liverpool

Locations

Intensive Care Unit, Royal Liverpool University Hospital

Liverpool, , United Kingdom

Countries

United Kingdom

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

UoL001367

Identifier Type: -

Identifier Source: org_study_id