Muscle Wasting in the Critically Ill

NCT03770442 | Completed DMC FDA Device

• 1 other identifier: UoL001367
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Muscle Weakness

Keywords

ICU acquired weakness (ICU-AW); FES; Functional Electrical Stimulation; Rehabilitation

Outcome Measures

Primary Outcomes (14)

• Ultrasound assessment of rectus femoris - Change in cross sectional area (cm2)

  Measurement of cross-sectional area of rectus femoris (cm2)

  Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.

• Ultrasound assessment of rectus femoris - Change in muscle layer thickness (cm)

  Measurement on muscle layer thickness of rectus femoris (cm)

  Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.

• Ultrasound assessment of anterior thigh musculature - Change in muscle layer thickness (cm)

  Measurement of combined muscle layer thickness of rectus femoris and vastus intermedius (cm)

  Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.

• Ultrasound assessment of vastus lateralis - change in muscle layer thickness (cm)

  Measurement of the thickness of the vastus lateralis between the superficial and deep aponeuroses (cm)

  Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.

• Ultrasound assessment of vastus lateralis - change in fascicle pennation angle (degrees)

  Measurement of the pennation angle of the muscle fascicles as they insert into the deep aponeuroses of the vastus lateralis muscle (degrees)

  Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.

• Ultrasound assessment of vastus lateralis - change in fascicle length (cm)

  This is a single measure, derived by trigonometry (the Sine of the pennation angle multiplied by the muscle thickness).

  Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.

• Ultrasound assessment of the medial head of gastrocnemius - change in muscle thickness (cm)

  Measurement of the thickness of the medial head of the gastrocnemius between the superficial and deep aponeuroses (cm)

  Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.

• Ultrasound assessment of the medial head of gastrocnemius - change in fascicle pennation angle (degrees)

  Measurement of the pennation angle of the muscle fascicles as they insert into the deep aponeuroses of the medial head of gastrocnemius (angles)

  Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.

• Ultrasound assessment of the medial head of gastrocnemius - change in fascicle length (cm)

  This is single measure which is mathematically derived by trigonometry using the known pennation angle (degrees) and thickness (cm): the Sine of the pennation angle multiplied by the muscle thickness.

  Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.

• Ultrasound assessment of the rectus abdominis muscle - change in muscle layer thickness (cm)

  Measurement of rectus abdominis muscle layer thickness - (cm)

  Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.

• Diaphragm thickness assessment by ultrasound - change in end expiratory thickness (mm)

  Assessment of thickness at end expiration (mm)

  Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.

• Diaphragm thickness assessment by ultrasound - change in end inspiratory thickness (mm)

  Assessment of thickness at end inspiration (mm)

  Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.

• Diaphragm thickness assessment by ultrasound - change in thickening fraction (%)

  Assessment of thickening fraction, derived mathematically from thicknesses at inspiration and expiration (%)

  Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.

• Ultrasound assessment of change in diaphragmatic excursion (cm)

  Assessment of maximal excursion of diaphragm, measured with M-mode ultrasonography (mm)

  Ultrasounds taken on day 1, 3, 5, 7, 10 and 14, and at 3 month follow up.

Secondary Outcomes (20)

• Measurement of change in blood biomarkers (microRNA analysis for markers of muscle loss, expressed as a percentage fold increase/decrease compared to baseline).

  Samples taken on days 1, 5, 10 and 14

• Measurement of change in urinary biomarkers (microRNA analysis for markers of muscle loss, expressed as a percentage-fold increase/decrease compared to baseline).

  Samples taken on days 1, 5, 10 and 14

• Measurement of the number of biomarkers expressed from muscle biopsies (microRNA analysis for markers of muscle loss, expressed as the number and type of micro-RNAs expressed within the samples).

  Samples taken on day 1 and 14

• Measurement of muscle fibre cross sectional area from muscle biopsies (mm2)

  Samples taken on day 1 and 14

• Follow up testing - Distance achieved in a 6 minute walk test, metres)

  At 3 month follow up

Study Arms (2)

Cycling with FES

EXPERIMENTAL

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).

Device: Cycling with FES

Control - routine physiotherapy

ACTIVE COMPARATOR

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

Other: Routine physiotherapy

Interventions

Cycling with FES DEVICE

As described already

Also known as: RT-300 Supine, Restorative Therapies

Cycling with FES

Routine physiotherapy OTHER

As described already

Control - routine physiotherapy

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Liverpool: lead

Study Sites (1)

Intensive Care Unit, Royal Liverpool University Hospital

Liverpool, L7 8XP, United Kingdom

Location

MeSH Terms

Conditions

Muscle Weakness

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Study Officials

• Ingeborg D Welters

  University of Liverpool

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Ultrasound images will be labelled by their participant number, and not by intervention. Therefore, when image analysis takes place, the investigators will not know whether the images come from somebody who received cycling sessions or the control group. Tissue samples will be treated in the same way. In follow up sessions, participants will be asked not to reveal if they can remember whether they cycled or not.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Lecturer, Institute of Aging and Chronic Disease

Study Record Dates

• First Submitted: October 15, 2018
• First Posted: December 10, 2018
• Study Start: January 14, 2019
• Primary Completion: November 1, 2020
• Study Completion: November 1, 2020
• Last Updated: November 4, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)