Vascular Health With Immobilization and Exercise Training

Study Overview
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Brief Summary
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The study includes healthy young habitually active subjects. All subjects are subjected to two weeks of immobilization of one leg followed by four weeks of training of both legs. The subjects are randomized to either one-leg training of the non-immobilized leg during the two-week immobilization period or to no training of the non-immobilized leg during the immobilization period. Measures include skeletal muscle morphology, markers of angiogenesis and apoptosis, muscle metabolic markers, vascular function, vascular proteins and performance.

Detailed Description
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One leg of young healthy subjects will be immoblized for two weeks. Changes in angiogenic proteins and markers of apoptosis in muscle tissue and muscle extracellular fluid will be determined in both legs and in parallel the functional consequences of immobilization will be assessed. Vascular function and vascular proteins will also be determined. In order to understand how the oxidative capacity of the muscle is altered in parallel with changes in capillarization, markers of mitochondria will be measured .Half of the subjects will be randomized to single-leg training during the immobilization period to assess whether simultaneous training reduces the loss of capillaries, muscle function and vascular function in the immobilized leg. After the immobilization period the study participants will train the immobilized leg and the control leg for four weeks by moderate to intense interval cycle training and the same parameteres as during immobilization will be assessed in both legs. The study will also include measurements of circulating compounds and platelets in blood.

Official Title
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Impact of Training on Skeletal Muscle Vascular and Metabolic Changes With Limb Immobilization

Conditions
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Immobilization, Tonic, Physical Activity

Intervention / Treatment
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* Other: Immobilization
* Other: Training with non immobilized leg
* Other: Exercise training with both legs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy BMI <25 Habitually/moderately physically active Exclusion Criteria: Known chronic medical disorder Smoking Excessive alcohol intake Known genetic/familial predisposition for thrombosis Hormonal birth control High level strength or endurance training on a regular basis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel randomized to training or no training of non-immobilized leg during immobilization of the other leg
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Immobilization<br>After baseline studies, the subjects will have one leg immobilized by full length plaster for two weeks. During the two weeks, the other leg will not be trained. After the two weeks the subjects will train both legs for four weeks. | Other: Immobilization<br>* Full length cast of one leg R/L randomized<br>Other: Exercise training with both legs<br>* Exercise training will be conducted regularly on a cycle ergometer during a four week period<br>|
| Active Comparator: Training of non-immobilized leg<br>After baseline studies, the subjects will have one leg immobilized by full length plaster for two weeks. During the two weeks, the other leg will be trained. After the two weeks the subjects will train both legs for four weeks. | Other: Immobilization<br>* Full length cast of one leg R/L randomized<br>Other: Training with non immobilized leg<br>* Exercise training will be conducted with the non-immobilized leg during the immobilization period of two weeks<br>Other: Exercise training with both legs<br>* Exercise training will be conducted regularly on a cycle ergometer during a four week period<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Angiogenesis | Skeletal muscle capillarization-comparison between legs | Change from baseline to after 2 weeks of immobilization | 
| Vascular function | Measurements of skeletal muscle blood flow by ultrasound doppler in response to infusion of vasodilators/constrictors-comparison between legs | Change from baseline to after 2 weeks of immobilization | 
| Angiogenesis | Skeletal muscle capillarization-comparison between legs | Change from after immobilization to after 4 weeks of training | 
| Vascular function | Measurements of skeletal muscle blood flow by ultrasound doppler in response to infusion of vasodilators/constrictors-comparison between legs | Change from after immobilization to after 4 weeks of training | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vascular and metabolic proteins | Proteins of importance for vascular function and muscle metabolism measured in muscle biopsy samples, skeletal muscle interstitial fluid and plasma-comparison between legs | Change from baseline to after 2 weeks of immobilization and from after immobilization to after 4 weeks of training | 
| Arterial blood pressure | Measured by sphygmomanometer and intra-arterially | Change from baseline to after 2 weeks of immobilization and from after immobilization to after 4 weeks of training | 
| Knee extensor performance | Measurements of maximal power and endurance-comparison between legs | Change from baseline to after 2 weeks of immobilization and from after immobilization to after 4 weeks of training | 
| Maximal oxygen uptake | Measured by gas analysis during an incremental ergometer cycle protocol | Change from baseline to after 2 weeks of immobilization and from after immobilization to after 4 weeks of training | 
| Body composition | Measurements by dual energy x-ray absorptiometry | Change from baseline to after 2 weeks of immobilization and from after immobilization to after 4 weeks of training | 
| Skin microcirculation | Measurements of skin blood flow and morphology and relevant proteins in skin biopsies | Change from baseline to after 2 weeks of immobilization and from after immobilization to after 4 weeks of training | 
| Markers of bone metabolism | Measurements of bone markers in plasma | Change from baseline to after 2 weeks of immobilization and from after immobilization to after 4 weeks of training | 
| Markers of angiogenesis | Measurement of angiogenic and apoptotic factors-comparison between legs | Change from baseline to after 2 weeks of immobilization and from after immobilization to after 4 weeks of training | 
| Vascular function-non-invasive | Measurements of skeletal muscle blood flow at rest, during passive movement, during exercise, after five min of occlusion and during infusion of vasodilators and constrictors-comparison between legs | Change from baseline to after 2 weeks of immobilization and from after immobilization to after 4 weeks of training | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immobilization, Angiogenesis, Skeletal muscle, Exercise training, Vascular function