Anterior Cruciate Ligament Reconstruction
Conditions
Keywords
AirBand
Brief summary
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
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
Interventions
DEVICEAirBand
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.
DEVICEuninflated AirBand
Uninflated AirBand will be used as the control intervention during the session in which BFR is not performed
Sponsors
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. Provision of signed and dated informed consent form 2. Stated willingness to comply with all study procedures and availability for two study visits at least 1 week apart 3. All genders, between 18 and 60 years of age 4. 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
1. Serious medical conditions including cardiovascular, metabolic (diabetes), rheumatologic, pulmonary, or musculoskeletal. 2. Multiple ligament ruptures or trauma 3. Rheumatoid arthritis or other significant comorbidities 4. Lower extremity vascular pathology, including history of deep vein thrombosis 5. Those with a history of sickle cell trait or disease 6. Use of anticoagulant medications 7. Pregnancy 8. Treatment with another investigational drug or other intervention within one month of Study Day 1 9. Current smoker or tobacco use within 3 months of Study Day 1 10. Febrile illness within 2 weeks of Study Day 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in catecholamines concentrations | Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise | 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. |
| Change in fatty acid concentrations | Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise | 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. |
| Change in insulin concentrations | Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise | Insulin may range from 0 to 100 uU/ml. Higher insulin may indicate a greater stress response. |
| Change in glucagon concentrations | Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise | Glucagon may range from 0 to 500 pM. Higher glucagon may indicate lower blood glucose concentrations. |
| Change in Leukocyte metabolic gene expression | Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise | 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. |
| Change in leukocyte substrate preference | Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise | 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. |
| Change in amino acids concentrations | Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise | 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). |
| Change in glucose concentrations | Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise | Glucose may be between 4 and 15 mM. Higher glucose may be indicative of diabetes. |
| Change in lactate concentrations | Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise | Lactate may be between 0.2 and 8 mM. Higher lactate may be indicative of a more intense exercise response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Whether the immunometabolic response correlates with patient-reported soreness following a physical therapy training session. | Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise | 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. |
| Change in creatine kinase | Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise | Creatine kinase concentration |
| Whether a baseline immunometabolic blueprint predicts the immunometabolic response to resistance training or to BFR. | Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise | Correlation between Outcomes 1-9 at 0, 30 and 60 minutes after training, to Outcomes 1-9 before training |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRachel Perry, PhD
Yale University
Outcome results
None listed