Progressive Rehabilitation Therapy in Patients With Advanced Lung Disease

• ClinicalTrials.gov Identifier: NCT03562728
• Recruitment Status: Active, not recruiting
• First Posted: June 19, 2018
• Last Update Posted: December 10, 2021
• Sponsor: University of Maryland, Baltimore
• Information provided by (Responsible Party): Irina Timofte, University of Maryland, Baltimore

Study Description

Brief Summary:

The International Society of Heart and Lung Transplantation Registry data shows that there is a growing population of critically ill patients with advanced lung disease undergoing lung transplantation.

The goal of our study is to evaluate the role of intensive physical therapy for patients with advanced lung disease requiring transplant or ECMO(extracorporeal membrane oxygenation)- bridge to transplant with emphasis on the restoration of functional independence and prevention of functional declines after lung transplantation.

The project is a designed as a randomized prospective research study investigating the impact of a multi-modal rehabilitation program(MRP), which incorporates neuromuscular electric stimulation(NMES), strength and mobility training, and nutritional supplementation(NS) in ameliorating the loss of muscle mass and strength, and lower extremity balance, strength and coordination that will decrease time on the ventilator or ECMO, stay in the ICU and hospital.

Condition or disease	Intervention/treatment	Phase
Advanced Lung Disease; Lung Transplant; Extracorporeal Membrane Oxygenation	Device: MRP and NMES(neuromuscular electric stimulation); Other: Standard of Care	Not Applicable

Detailed Description:

Intensive rehabilitation is recognized as an essential component to successful outcomes for post procedure recovery after a major cardio-thoracic procedure. The investigators propose a unique multi-modal rehabilitation program (MRP) that combines a step-up physical therapy protocol with neuromuscular electric stimulation (NMES), nutritional supplementation (NS), occupational therapy and pulmonary rehabilitation techniques to achieve improved functional outcomes for advanced lung disease patients requiring transplantation or ECMO-bridge to transplant. The investigators hypothesized that a progressive rehabilitation program, incorporating neuromuscular electric stimulation, strength and balance training, and nutritional supplementation with essential amino acids will reduce sarcopenia and loss of functional mobility in patients with advanced lung disease requiring transplantation or ECMO-bridge to transplant.

The purpose of this study is to determine the effectiveness of a progressive rehabilitation program, which incorporates neuromuscular electric stimulation, strength and mobility training, and nutritional supplementation in ameliorating 1) the loss of muscle mass and strength, and lower extremity balance, strength and coordination, 2) time on the ventilator or ECMO, stay in the intense care unit and hospital, and 3) return home and quality of life compared to usual ICU care.

The investigators propose a prospective, randomized interventional trial assessing the effectiveness of the program in decreasing adverse post-transplant outcomes compared to usual care. All advanced lung disease patients listed for transplantation or requiring ECMO cannulation will be screened for this study according to the inclusion and exclusion criterion. The patients will be randomized to either the treatment arm or usual care within 72 hours after the procedure (transplant or ECMO cannulation if patient requires ECMO-bridge to transplant). All groups of patients will undergo an initial global assessment of functional capabilities after listing for lung transplantation and then again within 72 hours after cardio-thoracic procedure (transplant or ECMO cannulation). Patients in the treatment arm will receive additional physical therapy that include: arm and leg exercises, using light weight machines, hand weights, or rubber bands, exercise machines such as portable arm or seated bikes. The treatment group will receive exercise therapy plus therapy with an electric stimulator device. This device uses weak electric impulses to involuntarily exercise the muscles (one-two sessions a day, with each session starting off at 10 minutes, then increasing to a maximum of 30 minutes). Subjects receiving the intervention will receive daily treatment using the neuromuscular electric stimulation unit. Four muscle groups (quadriceps and dorsiflexors bilaterally) will be stimulated using 3x5 inch surface electrodes (quadriceps) and 2x4 inch (dorsiflexors). In addition, patients in the experimental group will receive nutrition supplementation with essential amino acids 3 times a day in their feeding to prevent muscle breakdown and promote positive nitrogen balance. Comprehensive re-assessments are repeated on a weekly basis and the therapy will be adjusted to the patient's clinical status.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Assessing the Functional Impact of Progressive Rehabilitation Therapy in Patients With Advanced Lung Disease Requiring Lung Transplantation or ECMO- Bridge to Transplant
• Actual Study Start Date: January 13, 2019
• Estimated Primary Completion Date: September 1, 2023
• Estimated Study Completion Date: November 1, 2023

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: ECMO- Bridge to Transplant; Interventions: MRP+MNES(neuromuscular electric stimulation).Patients in the treatment arm will receive additional physical therapy(arm and leg exercises, using light weight machines, hand weights, or rubber bands, exercise machines such as portable arm or seated bikes) as well as therapy with an electric stimulator device. This device uses weak electric impulses to involuntarily exercise the muscles(one-two sessions a day).Four muscle groups(quadriceps and dorsiflexors bilaterally) will be stimulated using surface electrodes .In addition, patients in the experimental group will receive nutrition supplementation with essential amino acids 3 times a day in their feeding to prevent muscle breakdown and promote positive nitrogen balance.	Device: MRP and NMES(neuromuscular electric stimulation); nutrition supplementation includes addition of essential amino acids 3 times a day to feeding; Other Name: Dietary Supplement(NS)
ECMO- Bridge to Transplant Control Group; Interventions: standard of care Patients are not going to receive any additional intervention.	Other: Standard of Care; Patients in the control group are going to receive standard of care
Active Comparator: Transplant; Interventions: MRP+MNES(neuromuscular electric stimulation).Patients in the treatment arm will receive additional physical therapy(arm and leg exercises, using light weight machines, hand weights, or rubber bands, exercise machines such as portable arm or seated bikes) as well as therapy with an electric stimulator device. This device uses weak electric impulses to involuntarily exercise the muscles(one-two sessions a day).Four muscle groups(quadriceps and dorsiflexors bilaterally) will be stimulated using surface electrodes .In addition, patients in the experimental group will receive nutrition supplementation with essential amino acids 3 times a day in their feeding to prevent muscle breakdown and promote positive nitrogen balance.	Device: MRP and NMES(neuromuscular electric stimulation); nutrition supplementation includes addition of essential amino acids 3 times a day to feeding; Other Name: Dietary Supplement(NS)
Transplant Control Group; Interventions: standard of care. Patients are not going to receive any additional intervention.	Other: Standard of Care; Patients in the control group are going to receive standard of care

Outcome Measures

Primary Outcome Measures :

1. Global muscle strength [ Time Frame: 14 days ]
   Muscle group strength is obtained using hand held dynamometer
2. Mobility status [ Time Frame: 14 days ]
   Mobility status is assessed with 6 minute walk distance
3. Muscle mass [ Time Frame: 14 days, ]
   Muscle mass measurement of lower extremity muscle volume using ultrasound scan or computer tomography

Secondary Outcome Measures :

1. Time on the ventilator or ECMO [ Time Frame: 14 days, 1 month ]
   Measured as ECMO or ventilator days
2. Stay in the ICU and hospital [ Time Frame: 14 days, 1,3month ]
   Measured as days in the ICU and hospital

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Advanced lung disease requiring lung transplantation
• Advanced lung disease requiring ECMO bridge to lung transplantation
• Patient or legally authorized representative are able to provide written or witnessed verbal consent.

Exclusion Criteria:

• Unable to obtain consent from patient or family member
• Advanced lung disease but not transplant candidate due to other comorbidities
• Patient is deemed unsafe for rehabilitation by the transplant physician

Contacts and Locations

Locations

United States, Maryland

University of Maryland

Baltimore, Maryland, United States, 21201

Sponsors and Collaborators

University of Maryland, Baltimore

Investigators

• Principal Investigator: Irina Timofte; University of Maryland, College Park

More Information

Publications:

Downs AM. Physical therapy in lung transplantation. Phys Ther. 1996 Jun;76(6):626-42. Review.

Puthucheary ZA, Rawal J, McPhail M, Connolly B, Ratnayake G, Chan P, Hopkinson NS, Phadke R, Dew T, Sidhu PS, Velloso C, Seymour J, Agley CC, Selby A, Limb M, Edwards LM, Smith K, Rowlerson A, Rennie MJ, Moxham J, Harridge SD, Hart N, Montgomery HE. Acute skeletal muscle wasting in critical illness. JAMA. 2013 Oct 16;310(15):1591-600. Erratum in: JAMA. 2014 Feb 12;311(6):625. Padhke, Rahul [corrected to Phadke, Rahul].

Vogiatzis I, Terzis G, Nanas S, Stratakos G, Simoes DC, Georgiadou O, Zakynthinos S, Roussos C. Skeletal muscle adaptations to interval training in patients with advanced COPD. Chest. 2005 Dec;128(6):3838-45.

Williams TJ, Patterson GA, McClean PA, Zamel N, Maurer JR. Maximal exercise testing in single and double lung transplant recipients. Am Rev Respir Dis. 1992 Jan;145(1):101-5.

Vogiatzis I, Nanas S, Roussos C. Interval training as an alternative modality to continuous exercise in patients with COPD. Eur Respir J. 2002 Jul;20(1):12-9.

Chambers DC, Yusen RD, Cherikh WS, Goldfarb SB, Kucheryavaya AY, Khusch K, Levvey BJ, Lund LH, Meiser B, Rossano JW, Stehlik J; International Society for Heart and Lung Transplantation. The Registry of the International Society for Heart and Lung Transplantation: Thirty-fourth Adult Lung And Heart-Lung Transplantation Report-2017; Focus Theme: Allograft ischemic time. J Heart Lung Transplant. 2017 Oct;36(10):1047-1059. doi: 10.1016/j.healun.2017.07.016. Epub 2017 Jul 19. Review.

Alon G, V Smith G. Tolerance and conditioning to neuro-muscular electrical stimulation within and between sessions and gender. J Sports Sci Med. 2005 Dec 1;4(4):395-405. eCollection 2005 Dec.

• Responsible Party: Irina Timofte, Assistant Professor, University of Maryland, Baltimore
• ClinicalTrials.gov Identifier: NCT03562728
• Other Study ID Numbers: HP-00080970
• First Posted: June 19, 2018
• Last Update Posted: December 10, 2021
• Last Verified: December 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Information will be shared only with the investigators that are actively involved in the study

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Irina Timofte, University of Maryland, Baltimore:

Transplant; ECMO; Sarcopenia; Deconditioning; Physical therapy

Additional relevant MeSH terms:

Lung Diseases; Respiratory Tract Diseases