Immunometabolic Mechanisms of Blood Flow Restriction (BFR) Training After Anterior Cruciate Ligament Reconstruction

Study Overview
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Brief Summary
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This is a crossover phase 4 study to evaluate the impact of blood flow restriction on immunometabolism and gene expression in immune cells in individuals undergoing rehabilitation from anterior cruciate ligament reconstruction.

Detailed Description
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This is a single-blind crossover phase 4 study in which participants will be randomized as to the order in which each of two sessions are completed. Although all analyses will be performed by a blinded investigator and participants will wear an uninflated AirBand as the control intervention during the session in which BFR is not performed, participants will likely know which of the two interventions is being performed on which study day. The AirBands will be placed at each of the two training sessions and inflated while an ultrasound probe is placed over the femoral artery. The cuff will be inflated until the artery reaches 60% occlusion. The force will be applied using a wireless Bluetooth signal; participants will not be asked to adjust the device. Participants will be observed by a certified Personal Therapist throughout the training session in order to determine compliance and ensure safety as is standard protocol for a physical therapy session. The study team hypothesizes that the BFR will: Promote an anabolic immunometabolic signature, reflected in the composition of serum amino acid concentrations and anabolic hormone content Enhance anaerobic glycolysis in leukocytes (which has been associated with increased activation in other settings (Marelli-Berg and Jangani, 2018; Pearce and Pearce, 2013)) Increase leukocyte glucose and pyruvate concentrations, which corresponds to acute energy provision to promote repair

Official Title
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Immunometabolic Mechanisms of Blood Flow Restriction Training After Anterior Cruciate Ligament Reconstruction

Conditions
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Anterior Cruciate Ligament Reconstruction

Intervention / Treatment
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* Device: AirBand
* Device: uninflated AirBand


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed and dated informed consent form Stated willingness to comply with all study procedures and availability for two study visits at least 1 week apart All genders, between 18 and 60 years of age In good general health without any underlying medical conditions or prior injury that would place the subject at risk of further injury/illness by participating in the study Exclusion Criteria: Serious medical conditions including cardiovascular, metabolic (diabetes), rheumatologic, pulmonary, or musculoskeletal. Multiple ligament ruptures or trauma Rheumatoid arthritis or other significant comorbidities Lower extremity vascular pathology, including history of deep vein thrombosis Those with a history of sickle cell trait or disease Use of anticoagulant medications Pregnancy Treatment with another investigational drug or other intervention within one month of Study Day 1 Current smoker or tobacco use within 3 months of Study Day 1 Febrile illness within 2 weeks of Study Day 1

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AirBand followed by uninflated AirBand<br>The order of study days will be randomized. participants will wear an uninflated AirBand as the control intervention during the session in which BFR is not performed, | Device: AirBand<br>* The AirBands will be placed at each of the two training sessions and inflated while an ultrasound probe is placed over the femoral artery. The cuff will be inflated until the artery reaches 60% occlusion. The force will be applied using a wireless Bluetooth signal; participants will not be asked to adjust the device. Participants will be observed by a certified Personal Therapist throughout the training session in order to determine compliance and ensure safety as is standard protocol for a physical therapy session.<br>Device: uninflated AirBand<br>* Uninflated AirBand will be used as the control intervention during the session in which BFR is not performed<br>|
| Experimental: Uninflated Airbnd followed by AirBand<br>The order of study days will be randomized. participants will wear an uninflated AirBand as the control intervention during the session in which BFR is not performed, | Device: AirBand<br>* The AirBands will be placed at each of the two training sessions and inflated while an ultrasound probe is placed over the femoral artery. The cuff will be inflated until the artery reaches 60% occlusion. The force will be applied using a wireless Bluetooth signal; participants will not be asked to adjust the device. Participants will be observed by a certified Personal Therapist throughout the training session in order to determine compliance and ensure safety as is standard protocol for a physical therapy session.<br>Device: uninflated AirBand<br>* Uninflated AirBand will be used as the control intervention during the session in which BFR is not performed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Leukocyte metabolic gene expression | Gene expression measured by RNAseq. Because of the nature of RNAseq it is not possible to provide a comprehensive list of gene expression that will be measured; however, genes of particular interest include Slc2a3, Slc2a1, Slc2a4, Slc16a3, PC, Pdha1, Acc1, Fasn. | Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise | 
| Change in leukocyte substrate preference | Fractional contributions of glucose and fatty acids to total mitochondrial oxidation will be measured. Each can fuel between 0 and 100% of total mitochondrial oxidation. | Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise | 
| Change in amino acids concentrations | Concentrations of all amino acids (alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamate, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine). Amino acid concentrations may be between 1 and 500 uM. Higher amino acid concentrations may indicate greater muscle breakdown (proteolysis). | Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise | 
| Change in glucose concentrations | Glucose may be between 4 and 15 mM. Higher glucose may be indicative of diabetes. | Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise | 
| Change in lactate concentrations | Lactate may be between 0.2 and 8 mM. Higher lactate may be indicative of a more intense exercise response. | Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise | 
| Change in fatty acid concentrations | Saturated and unsaturated fatty acid concentrations will be measured. Each fatty acid may range from 0 to 5 mM. Increased fatty acid concentrations may be indicative of a greater stress response to exercise. | Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise | 
| Change in insulin concentrations | Insulin may range from 0 to 100 uU/ml. Higher insulin may indicate a greater stress response. | Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise | 
| Change in glucagon concentrations | Glucagon may range from 0 to 500 pM. Higher glucagon may indicate lower blood glucose concentrations. | Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise | 
| Change in catecholamines concentrations | Epinephrine and norepinephrine (also known as adrenaline and noradrenaline) will be measured. They can range from 0-1000 nM. Higher catecholamide concentrations may indicate a greater stress response to training. | Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whether a baseline immunometabolic blueprint predicts the immunometabolic response to resistance training or to BFR. | Correlation between Outcomes 1-9 at 0, 30 and 60 minutes after training, to Outcomes 1-9 before training | Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise | 
| Whether the immunometabolic response correlates with patient-reported soreness following a physical therapy training session. | the soreness scale is 0 to 10, with 0 as no pain or soreness and 10 as pain or soreness as bad as it could possibly be. | Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise | 
| Change in creatine kinase | Creatine kinase concentration | Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AirBand