Effects of Different Exercise Training Modalities in Alpha-1 Antitrypsin Deficiency Patients

Study Overview
=================
Brief Summary
-----------------
Pulmonary rehabilitation (PR) including exercise training is highly effective by improving health-related quality of life, exercise capacity and symptoms in patients with chronic obstructive pulmonary disease (COPD). Therefore, PR is a main component in the management of COPD. In a former study patients with Alpha-1 Antitrypsin deficiency (A1ATD)-related COPD (genotype PiZZ) have been found to show smaller improvements in exercise capacity after a 3-week inpatient PR program compared to COPD patients without A1ATD (genotype PiMM)[1]. These between-group differences were mirrored by missing adaptations of the fatigue-resistant skeletal muscle fibre type I in A1ATD patients. This was in contrast to COPD patients without A1ATD who increased the proportion of this fibre type after PR. Myofibre type I is crucial because it enables patients for physical endurance activities (walking, cycling etc.) during their daily life. The aim of this study is to compare the effects of an exercise Training program with high vs. moderate Training intensity in order to find a Training modality which improves Training effects in A1ATD patients.

Official Title
-----------------
Effects of Moderate vs. High Intensity Exercise Training During Pulmonary Rehabilitation in Alpha-1 Antitrypsin Deficiency Patients

Conditions
-----------------
Chronic Obstructive Pulmonary Disease, Alpha 1-Antitrypsin Deficiency

Intervention / Treatment
-----------------
* Procedure: Exercise training


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: COPD patients with A1ATD (genotype PiZZ) COPD patients without A1ATD (genotype PiMM) Global initiative for chronic obstructive lung disease (GOLD) stage III-IV Medical Treatment according to recent A1ATD guidelines Exclusion Criteria: General exclusion criteria for physical Training such as acute coronary Syndrome, acute myo- or pericarditis, acute lung embolism, acute heart failure, orthopedic comorbidities which prevent patients from participating in exercise Training program. No written informed consent Non-compliance

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomized into two Intervention Groups (high vs. moderate Training intensity).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High training intensity<br>Exercise Training with high intensities consists of a cycling Interval Training at 100% of the individual Peak work rate, resistance Training for 3 sets à 8 repetitions and squats on a Vibration plate. | Procedure: Exercise training<br>* Patients perform an exercise Training program of 3 weeks Duration including endurance Training, resistance Training and squat Training. This program is part of an inpatient pulmonary Rehabilitation.<br>|
| Active Comparator: moderate training intensity<br>Exercise Training with moderate intensities consists of a cycling endurance Training at 60% of the individual Peak work rate, resistance Training for 3 sets à 20 repetitions and squats on the floor. | Procedure: Exercise training<br>* Patients perform an exercise Training program of 3 weeks Duration including endurance Training, resistance Training and squat Training. This program is part of an inpatient pulmonary Rehabilitation.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endurance shuttle walk test (ESWT) | The ESWT is performed at 85% of the Peak gate Speed, measured during the Initial incremental shuttle walk test. | Change in the duration of the ESWT from day 1 to day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxygen saturation | Outcome will be assessed at the the time Point of the end of the shortest ESWT (isotime). | Change in the oxygen saturation at isotime from day 1 to day 21 | 
| Heart rate | Outcome will be assessed at the the time Point of the end of the shortest ESWT (isotime). | Change in the heart rate at isotime from day 1 to day 21 | 
| Partial pressure of carbon dioxide (CO2) | Parameter will be measured by Sentec (R) device. Outcome will be assessed at the the time Point of the end of the shortest ESWT (isotime). | Change in the partial pressure of CO2 at isotime from day 1 to day 21 | 
| Lactate concentration | Outcome will be assessed at the the time Point of the end of the shortest ESWT (isotime). | Change in lactate concentration at isotime from day 1 to day 21 | 
| Perceived Dyspnea | Dyspnea will be rated on a 0 to 10-point BORG scale where lower values represent less dyspnea and vice versa. The total score will be assessed at the the time Point of the end of the shortest ESWT (isotime). | Change in perceived dyspnea at isotime from day 1 to day 21 | 
| Strength capacity in knee extension | Strength will be measured by a Hand Held Dynamometer (Microfet (R)). | Change in strength from day 1 to day 21 | 
| Balance performance | absolute path length will be measured on a force plate (Leonardo (R)) during the Tandem stance | Change in balance performance from day 1 to day 21 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pulmonary rehabilitation, Exercise training, Alpha-1 Antitrypsin deficiency