Vascular Health With Immobilization and Exercise Training

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

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.

Study Overview

• Status: Completed
• Conditions: Physical Activity; Immobilization, Tonic
• Intervention / Treatment: Other: Immobilization; Other: Exercise training with both legs; Other: Training with non immobilized leg

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • University of Copenhagen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Immobilization; 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; Full length cast of one leg R/L randomized; Other: Exercise training with both legs; Exercise training will be conducted regularly on a cycle ergometer during a four week period
Active Comparator: Training of non-immobilized leg; 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; Full length cast of one leg R/L randomized; Other: Exercise training with both legs; Exercise training will be conducted regularly on a cycle ergometer during a four week period; Other: Training with non immobilized leg; Exercise training will be conducted with the non-immobilized leg during the immobilization period of two weeks

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Copenhagen
• Collaborators: Radboud University Medical Center; University of Leeds; Johannes Gutenberg University Mainz; Liverpool John Moores University

Publications and helpful links

General Publications

• Gliemann L, Rytter N, Jorgensen TS, Piil P, Carter H, Nyberg M, Grassi M, Daumer M, Hellsten Y. The Impact of Lower Limb Immobilization and Rehabilitation on Angiogenic Proteins and Capillarization in Skeletal Muscle. Med Sci Sports Exerc. 2021 Sep 1;53(9):1797-1806. doi: 10.1249/MSS.0000000000002665.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2017
• Primary Completion (Actual): October 20, 2022
• Study Completion (Actual): October 20, 2022

Study Registration Dates

• First Submitted: February 5, 2017
• First Submitted That Met QC Criteria: February 10, 2017
• First Posted (Actual): February 15, 2017

Study Record Updates

• Last Update Posted (Actual): November 2, 2022
• Last Update Submitted That Met QC Criteria: November 1, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Angiogenesis; Exercise training; Vascular function; Skeletal muscle; Immobilization
• Other Study ID Numbers: ANG-CV- IMMOB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No