Muscle WeaknessExPrEsNCT02509520
Assessing The Effects of Exercise, Protein, and Electric Stimulation On Intensive Care Unit Patients Outcomes
A study testing MPR and High Protein Supplement (HPRO) and Neuromuscular Electric Stimulation (NMES) in people with Muscle Weakness and Critical Illness, run by University of Maryland, Baltimore at 1 site in United States.
Trial summary
Elderly patients who experience a prolonged ICU stay are at high risk for developing post intensive care unit syndrome (PICS), a serious medical condition manifested by loss of muscle mass, weakness, malnutrition and neurocognitive decline. Read more about this study
- Who is it for?
- Ages 45 years and older
- Conditions the study is for
- Muscle Weakness, Critical Illness, Sarcopenia
- What is being tested?
- MPR and High Protein Supplement (HPRO) and Neuromuscular Electric Stimulation (NMES)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2015to 1 May 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 45 years
- Respiratory insufficiency requiring mechanical ventilation (MV)
- ICU presentation < 6 days
- Patient or legally authorized representative able to provide written or witnessed verbal informed consent in English
- All four limbs intact and mobile
- Eligible for and able to participate in physical therapy
- Pre admission Barthel Index >70
Who cannot join
- Acute kidney injury with a glomerular filtration rate < 30 ml/min
- Diagnosis of severe organ dysfunction including end stage liver disease or cirrhosis
- Diagnosis of active cancer
- Acute or chronic organ transplant rejection
- Exceedingly high mechanical ventilator settings (FiO2>60%, PEEP>12) or alternative modes of mechanical ventilation (inverse ratio pressure control, airway pressure release ventilation)
- Severe functional impairment or physical impairment to rehabilitation
Show all 9Show fewer
- On high dose vasopressor agents (> 5mcg of norepinephrine or equivalent)
- Liver function tests > 2.5 x normal limits (normal reference ranges include AST between 10 and 40 units/L or ALT between 7 and 56 units/L)
- Chronic dementia or cognitive impairment
Trial locations and contacts
1 site in 1 country.
United States1 site
U of Maryland, Baltimore, Professional Schools IRB
Baltimore, Maryland, 21201
About this study
Official title: Rehabilitation, NMES and High Protein to Reduce Post ICU Syndrome in the Elderly
Elderly patients who experience a prolonged ICU stay are at high risk for developing post intensive care unit syndrome (PICS), a serious medical condition manifested by loss of muscle mass, weakness, malnutrition and neurocognitive decline. PICS often leads to chronic disability, prolonged mechanical ventilation and the need for costly extended stays in long term care facilities (LTCs). The investigators' preliminary study shows attempts at rehabilitating patients who have already developed PICS are minimally effective, resulting in only modest improvements in functionality. This project will determine the effects of mobility-based physical rehabilitation (MPR) combined with neuromuscular electric stimulation (NMES) and high protein supplementation (HPRO) early in a patients ICU stay on preventing PICS related musculoskeletal and functional deficits, and improving clinical outcomes.
Read the detailed description
Older, critically ill patients who survive their ICU stay frequently develop post-ICU syndrome (PICS) - a condition manifested by sarcopenia, weakness, malnutrition and neurocognitive decline - which occurs as a result of a critical illness, prolonged bed rest, catabolism, and polypharmacy. PICS frequently leads to chronic disability, prolonged mechanical ventilation (MV), functional deficits, and the need for extended rehabilitation in long term care facilities (LTCs). As the majority of patients admitted to ICUs are ≥ 65 years old, many of these patients are at high risk for PICS. Since the care of ICU patients is primarily focused on the medical management of the acute critical illness, there are limited resources and strategies available to prevent PICS. Evidence suggests mobility-based physical rehabilitation (MPR) combined with resistive training with neuromuscular electric stimulation (NMES) and high protein diets (HPRO) containing essential amino acids can mitigate the loss of muscle mass and function during bed rest in the elderly. The investigators hypothesize that preventive therapy involving the addition of both NMES and HPRO to MPR early and throughout the ICU and hospital stay can mitigate PICS-associated sarcopenia, malnutrition, and immobility to confer valuable health benefits toward recovery. To test this, the investigators will use a 2x2 factorial design in which older, MV ICU patients will all receive comprehensive ICU care and MPR, then be randomized to one of 4 groups: 1) MPR+NMES, 2) MPR+HPRO, 3) all 3 together, or 4) MPR alone (control), to determine independent and combined effects of the interventions.
The Specific Aims are to 1) determine the effects of adding NMES and HPRO interventions to MPR on muscle mass, strength, and mobility function in older, critically ill MV patients while still in the ICU, and 2) determine the effects of adding NMES and HPRO interventions to MPR on the clinical outcomes of time to weaning from MV, ICU/hospital length of stay and discharge disposition of these patients.
This proposal capitalizes on the interdisciplinary collaboration among Pulmonary/Critical Care Intensivists, Physical Therapists, Geriatricians, Clinical Nutritionists, Statisticians and Nutrition and Metabolism clinical researchers examining the efficacy of the proposed comprehensive rehabilitation approach. The investigators' primary goal is to attenuate the severity of sarcopenia and functional decline in this older, critically ill population at risk for severe disability. Additionally, by focusing on maintaining skeletal muscle mass, function, and strength, the investigators hope to improve clinical outcomes. The investigators posit this combined therapy will mitigate PICS-associated disability and speed the recovery from critical illness in older, MV ICU patients. This project has high overall impact as the intervention is easily administered by hospital staff and may greatly reduce the physiological and functional declines while hastening recovery during acute ICU hospitalization in older adults.
- Conditions
- Muscle Weakness, Critical Illness, Sarcopenia
- Being tested
- MPR and High Protein Supplement (HPRO) and Neuromuscular Electric Stimulation (NMES)
- Keywords
- Nutritional supplementation, Neuromuscular Electric Stimulation, ICU acquired weakness, Post ICU Syndrome, sarcopenia
- Medical subject headings
- Muscle Weakness, Critical Illness, Sarcopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MPR and High Protein Supplement (HPRO) and Neuromuscular Electric Stimulation (NMES)Dietary supplement
The MPR provides strength and cardiopulmonary endurance training, which consist of exercises to promote function movements. Intensity is based on patient's hemodynamic responses and subjective report using Modified Borg Dyspnea Scale. Intensity, duration, or type of activity will be modified each session to achieve a moderately intense physiologic response. The NMES protocol requires self-adhesive surface electrodes be placed on quadriceps muscles and lower leg bilaterally, twice daily. This protocol is based on prior NMES protocols used to stimulate muscle protein synthesis in older diabetic patients, preserve muscle mass in intensive care patients and increase strength in older adults after knee replacement. The HPRO intervention is based on caloric needs, calculated using validated equations to maintain positive nitrogen balance. Protein will be supplemented as isolated amino acids twice/day to deliver ~15g of essential amino acids per serving, with a goal of 1.6 g/kg/day.
| Study group | Role | What they receive |
|---|---|---|
| Mobility-based Physical Rehab (MPR) | No intervention | ICU control group receiving only mobility based rehabilitation (MPR). |
| MPR and Neuromuscular Stimulation and HPRO | Active comparator | ICU group receiving mobility based rehabilitation and NMES and High protein supplementation. Receives: Dietary Supplement: MPR and High Protein Supplement (HPRO) and Neuromuscular Electric Stimulation (NMES) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Muscle mass
Muscle mass as measured by lower extremity muscle volume
Measured: 14 days
Global body strength
Muscle group strength as measured by hand held dynamometer and by hand grip strength
Measured: 14 days
Mobility status
Outcome as measured by combined 6 minute walk distance and gait speed
Measured: 14 days
Short Physical Performance Battery
Short Physical Performance battery will be assessed at baseline and at 7 and 14 days.
Measured: 14 days
Secondary outcomes (4)
Time to weaning
As measured by ventilator days
Measured: 14 days
ICU/Hospital length of stay
Days in the ICU, days in the hospital
Measured: 14 days
Discharge disposition
home, nursing home, acute rehabilitation, readmission, death, remains hospitalized
Measured: 30 days
Weaning success
proportion of patient successfully weaned with in a 14 day period, and eventually
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2015 (estimated)
- Study start1 May 2015
- Primary completion1 May 2027 (estimated)
- Study completion1 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Muscle WeaknessStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Avelino Verceles, University of Maryland, Baltimore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02509520
- Sponsor's protocol ID
- 00056749
- Acronym
- ExPrEs
- Status last verified
- Jun 2026
- First submitted
- 21 Jul 2015
- Last updated
- 2 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Verceles AC, Serra M, Davis D, Alon G, Wells CL, Parker E, Sorkin J, Bhatti W, Terrin ML. Combining exercise, protein supplementation and electric stimulation to mitigate muscle wasting and improve outcomes for survivors of critical illness-The ExPrES study. Heart Lung. 2023 Mar-Apr;58:229-235. doi: 10.1016/j.hrtlng.2022.11.013. Epub 2022 Dec 5.
PubMed 36473808
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rehabilitation, NMES and High Protein to Reduce Post ICU Syndrome in the Elderly
- ClinicalTrials.gov ID
- NCT02509520
- Acronym / sponsor ID
- ExPrEs / 00056749
- Conditions
- Muscle Weakness, Critical Illness, Sarcopenia
- Keywords
- Nutritional supplementation, Neuromuscular Electric Stimulation, ICU acquired weakness, Post ICU Syndrome, sarcopenia
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Study start
- 1 May 2015 (actual)
- Primary completion
- 1 May 2027 (estimated)
- Study completion
- 1 May 2027 (estimated)
- First posted
- 28 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Elderly patients who experience a prolonged ICU stay are at high risk for developing post intensive care unit syndrome (PICS), a serious medical condition manifested by loss of muscle mass, weakness, malnutrition and neurocognitive decline. PICS often leads to chronic disability, prolonged mechanical ventilation and the need for costly extended stays in long term care facilities (LTCs). The investigators' preliminary study shows attempts at rehabilitating patients who have already developed PICS are minimally effective, resulting in only modest improvements in functionality. This project will determine the effects of mobility-based physical rehabilitation (MPR) combined with neuromuscular electric stimulation (NMES) and high protein supplementation (HPRO) early in a patients ICU stay on preventing PICS related musculoskeletal and functional deficits, and improving clinical outcomes.
Detailed description
Older, critically ill patients who survive their ICU stay frequently develop post-ICU syndrome (PICS) - a condition manifested by sarcopenia, weakness, malnutrition and neurocognitive decline - which occurs as a result of a critical illness, prolonged bed rest, catabolism, and polypharmacy. PICS frequently leads to chronic disability, prolonged mechanical ventilation (MV), functional deficits, and the need for extended rehabilitation in long term care facilities (LTCs). As the majority of patients admitted to ICUs are ≥ 65 years old, many of these patients are at high risk for PICS. Since the care of ICU patients is primarily focused on the medical management of the acute critical illness, there are limited resources and strategies available to prevent PICS. Evidence suggests mobility-based physical rehabilitation (MPR) combined with resistive training with neuromuscular electric stimulation (NMES) and high protein diets (HPRO) containing essential amino acids can mitigate the loss of muscle mass and function during bed rest in the elderly. The investigators hypothesize that preventive therapy involving the addition of both NMES and HPRO to MPR early and throughout the ICU and hospital stay can mitigate PICS-associated sarcopenia, malnutrition, and immobility to confer valuable health benefits toward recovery. To test this, the investigators will use a 2x2 factorial design in which older, MV ICU patients will all receive comprehensive ICU care and MPR, then be randomized to one of 4 groups: 1) MPR+NMES, 2) MPR+HPRO, 3) all 3 together, or 4) MPR alone (control), to determine independent and combined effects of the interventions.
The Specific Aims are to 1) determine the effects of adding NMES and HPRO interventions to MPR on muscle mass, strength, and mobility function in older, critically ill MV patients while still in the ICU, and 2) determine the effects of adding NMES and HPRO interventions to MPR on the clinical outcomes of time to weaning from MV, ICU/hospital length of stay and discharge disposition of these patients.
This proposal capitalizes on the interdisciplinary collaboration among Pulmonary/Critical Care Intensivists, Physical Therapists, Geriatricians, Clinical Nutritionists, Statisticians and Nutrition and Metabolism clinical researchers examining the efficacy of the proposed comprehensive rehabilitation approach. The investigators' primary goal is to attenuate the severity of sarcopenia and functional decline in this older, critically ill population at risk for severe disability. Additionally, by focusing on maintaining skeletal muscle mass, function, and strength, the investigators hope to improve clinical outcomes. The investigators posit this combined therapy will mitigate PICS-associated disability and speed the recovery from critical illness in older, MV ICU patients. This project has high overall impact as the intervention is easily administered by hospital staff and may greatly reduce the physiological and functional declines while hastening recovery during acute ICU hospitalization in older adults.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mobility-based Physical Rehab (MPR) | No intervention | –ICU control group receiving only mobility based rehabilitation (MPR). |
| MPR and Neuromuscular Stimulation and HPRO | Active comparator | Dietary Supplement: MPR and High Protein Supplement (HPRO) and Neuromuscular Electric Stimulation (NMES)ICU group receiving mobility based rehabilitation and NMES and High protein supplementation. |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age ≥ 45 years
- Respiratory insufficiency requiring mechanical ventilation (MV)
- ICU presentation < 6 days
- Patient or legally authorized representative able to provide written or witnessed verbal informed consent in English
- All four limbs intact and mobile
Key exclusion criteria (9 listed)
- Acute kidney injury with a glomerular filtration rate < 30 ml/min
- Diagnosis of severe organ dysfunction including end stage liver disease or cirrhosis
- Diagnosis of active cancer
- Acute or chronic organ transplant rejection
- Exceedingly high mechanical ventilator settings (FiO2>60%, PEEP>12) or alternative modes of mechanical ventilation (inverse ratio pressure control, airway pressure release ventilation)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MPR and High Protein Supplement (HPRO) and Neuromuscular Electric Stimulation (NMES)The MPR provides strength and cardiopulmonary endurance training, which consist of exercises to promote function movements. Intensity is based on patient's hemodynamic responses and subjective report using Modified Borg Dyspnea Scale. Intensity, duration, or type of activity will be modified each session to achieve a moderately intense physiologic response. The NMES protocol requires self-adhesive surface electrodes be placed on quadriceps muscles and lower leg bilaterally, twice daily. This protocol is based on prior NMES protocols used to stimulate muscle protein synthesis in older diabetic patients, preserve muscle mass in intensive care patients and increase strength in older adults after knee replacement. The HPRO intervention is based on caloric needs, calculated using validated equations to maintain positive nitrogen balance. Protein will be supplemented as isolated amino acids twice/day to deliver ~15g of essential amino acids per serving, with a goal of 1.6 g/kg/day. | Dietary supplement | MPR and Neuromuscular Stimulation and HPRO |
Primary outcome
Muscle mass
Time frame: 14 days
Muscle mass as measured by lower extremity muscle volume
Global body strength
Time frame: 14 days
Muscle group strength as measured by hand held dynamometer and by hand grip strength
Mobility status
Time frame: 14 days
Outcome as measured by combined 6 minute walk distance and gait speed
Short Physical Performance Battery
Time frame: 14 days
Short Physical Performance battery will be assessed at baseline and at 7 and 14 days.
4 secondary outcomes
Time to weaning
Time frame: 14 days
ICU/Hospital length of stay
Time frame: 14 days
Discharge disposition
Time frame: 30 days
Weaning success
Time frame: 14 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2026.
- Derived from this study: PubMed 36473808Verceles AC, Serra M, Davis D, Alon G, Wells CL, Parker E, Sorkin J, Bhatti W, Terrin ML. Combining exercise, protein supplementation and electric stimulation to mitigate muscle wasting and improve outcomes for survivors of critical illness-The ExPrES study. Heart Lung. 2023 Mar-Apr;58:229-235. doi: 10.1016/j.hrtlng.2022.11.013. Epub 2022 Dec 5.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing MPR and High Protein Supplement (HPRO) and Neuromuscular Electric Stimulation (NMES) in people with Muscle Weakness and Critical Illness, run by University of Maryland, Baltimore at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 2 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Muscle mass (time frame: 14 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02509520, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2026.