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Prehabilitation on Fitness, Surgical Outcomes and Mitochondria Functionality in Patients With Esophageal Cancer

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ClinicalTrials.gov Identifier: NCT04673968
Recruitment Status : Recruiting
First Posted : December 17, 2020
Last Update Posted : December 17, 2020
Sponsor:
Information provided by (Responsible Party):
Chang Gung Memorial Hospital

Brief Summary:

The most often reported complications of patients with resectable esophageal malignancies are pulmonary (25~57%), which may cause increased intensive care unit utilization, prolonged length of hospital stay, increased mortality and medical expense. Also, neoadjuvant chemotherapy has a deleterious effect on patients' cardiopulmonary capacity, strength and muscle mass. Prehabilitation includes preoperative exercise training and nutrition management. The reporting outcome regarding whether it improves surgical outcomes is inconsistent. One of the reasons is that pulmonary complication tends to occur in patients with low cardiopulmonary fitness, but all studies included patients with all level of fitness.

Most of the chemotherapy interferes with cell division to inhibit tumor growth but is also harmful to mitochondria functionality. For example, Cisplatin and Paclitaxel, commonly used in esophageal cancer, alter mitochondria function, caused by disruption of respiratory chain function and increased production of reactive oxygen species. However, it remains unclear their negative effects on the oxidative phosphorylation capacity of mitochondria (OXPHOS). Furthermore, whether prehabilitation reverses this negative effect is scarcely explored.

Patients will be inquired to participate and randomized into prehabilitation or control group. The latter will undergo conventional therapy only, while the former will receive additional prehabilitation program. The prehabilitation program encompasses supervised and home-based aerobic, resistance training (large and inspiratory muscle) and nutrition management. The supervised exercise training will be performed right before or after the radiotherapy. Outcome variables are fitness-related testing [the 1st year], quality of life and surgical outcomes [the 2nd year] and mitochondria functionality (OXPHOS, membrane potential, matrix oxidant burden) [the 3rd year]. Evaluation is performed 3 times at baseline, before surgery and 4 weeks after surgery.


Condition or disease Intervention/treatment Phase
Esophageal Cancer Other: prehabilitation Not Applicable

Detailed Description:

Neoadjuvant chemotherapy has significantly improved patient outcomes. The majority of patients with resectable esophageal malignancies are considered for neoadjuvant treatment. However, esophagectomy and chemotherapy have disadvantages. Morbidity and mortality associated with esophagus resection remain high. The most often reported complications are pulmonary (25~57%), which may cause increased intensive care unit utilization, prolonged length of hospital stay, increased mortality and medical expense.

Also, neoadjuvant chemotherapy has a deleterious effect on patients' cardiopulmonary capacity, strength and muscle mass. Prehabilitation includes preoperative exercise training and nutrition management. The reporting outcome regarding whether it improves surgical outcomes is inconsistent. One of the reasons is that pulmonary complication tends to occur in patients with low cardiopulmonary fitness, but all studies included patients with all level of fitness. In the current investigation, only those with low cardiopulmonary fitness will be enrolled.

Most of the chemotherapy interferes with cell division to inhibit tumor growth but is also harmful to mitochondria functionality. For example, Cisplatin and Paclitaxel, commonly used in esophageal cancer, alter mitochondria function, caused by disruption of respiratory chain function and increased production of reactive oxygen species. However, it remains unclear their negative effects on the oxidative phosphorylation capacity of mitochondria (OXPHOS). Furthermore, whether prehabilitation reverses this negative effect is scarcely explored.

This is a three-year prospective randomized trial. Patients who suffer from locally-advanced esophageal cancer and will receive neoadjuvant chemoradiotherapy and operation in Chang Gung Memorial Hospital at Linkou will be inquired to participate. A total of 160 patients will be recruited expectedly and randomized into prehabilitation or control group. The latter will undergo conventional therapy only, while the former will receive additional prehabilitation program. The prehabilitation program encompasses supervised and home-based aerobic, resistance training (large and inspiratory muscle) and nutrition management. The supervised exercise training will be performed right before or after the radiotherapy. Outcome variables are fitness-related testing (cardiopulmonary exercise testing, 6-minute walk distance, handgrip, and body composition, maximal inspiratory pressure and muscle oxidative capacity) [the 1st year], quality of life and surgical outcomes (length of stay in the hospital and intensive care unit, surgical complication, perioperative pulmonary complications and medical expense) [the 2nd year] and mitochondria functionality (OXPHOS, membrane potential, matrix oxidant burden) [the 3rd year]. Evaluation is performed 3 times at baseline, before surgery and 4 weeks after surgery.

The investigators hypothesize that prehabilitation increases functional reserve to improve surgical outcomes [2nd year] in a subpopulation of patients with esophageal cancer who receive neoadjuvant chemo-radiotherapy plus having low cardiopulmonary fitness. It also reverses fitness decline during neoadjuvant chemotherapy [1st year], partly through amelioration of mitochondria functionality [3rd year]. The goal of the investigation is to provide an applicable prehabilitation model and establish its efficacy at clinical, tissue and cellular levels.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Efficacy of Prehabilitation on Fitness, Surgical Outcomes and Mitochondria Functionality in Patients With Esophageal Cancer Undergoing Neoadjuvant Chemotherapy
Actual Study Start Date : February 25, 2020
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : July 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: prehabilitation (P)
inhospital exercise training 5 times/week, 5~6 weeks during nCRT (neoadjuvant chemoraiotherapy); home exercise 5 times/week, 5~6 weeks, between completion of nCRT and before surgery
Other: prehabilitation
inhospital exercise training 5 times/week, 5~6 weeks during nCRT; home exercise 5 times/week, 5~6 weeks, between completion of nCRT and before surgery

No Intervention: control group (C)
no prehabilitation



Primary Outcome Measures :
  1. Exercise capacity of all participants by Cardiopulmonary Exercise Test (CPET) [ Time Frame: three years ]
    Cardiopulmonary Exercise Test

  2. Exercise capacity of fitness-related parameters: 6-minute walk distance [ Time Frame: three years ]
    Detection of 6-minute walk distance in meters

  3. Exercise capacity of fitness-related parameters: hand grip [ Time Frame: three years ]
    Detection of hand grip strength in kilograms

  4. Body composition [ Time Frame: three years ]
    Body composition analysis


Secondary Outcome Measures :
  1. Surgical outcomes of inpatient days [ Time Frame: three years ]
    length of stay in the hospital and intensive care unit in days

  2. Complications outcomes [ Time Frame: three years ]
    Preoperative and surgical complications analysis

  3. Mitochondria functionality [ Time Frame: three years ]
    Mitochondrial function of lymphocytes



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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • nonmetastatic esophageal cancer patients.
  • V'O2 < 21ml/min/kg
  • abnormality on spirometry.

Exclusion Criteria:

  • Resting heart rate greater than 100 beats per minute
  • Atrial fibrillation or flutter
  • Poor control of high blood pressure or diabetes
  • Patients with peripheral arterial occlusive disease
  • Patients with end-stage renal disease
  • Patients receiving anticoagulant therapy
  • Neurological instability

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04673968


Contacts
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Contact: Shu-Chun Huang, MD, PhD +88633281200 ext 5156 mr7171@cgmh.org.tw

Locations
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Taiwan
Chang Gung Memorial Hospital Recruiting
Taoyuan, Taiwan, 333
Contact: Shu-Chun Huang, MD, PhD         
Sponsors and Collaborators
Chang Gung Memorial Hospital
Investigators
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Principal Investigator: Shu-Chun Huang, MD, PhD Chang Gung Memorial Hospital
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Responsible Party: Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier: NCT04673968    
Other Study ID Numbers: 201901758B0
First Posted: December 17, 2020    Key Record Dates
Last Update Posted: December 17, 2020
Last Verified: December 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases