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

Official title

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

Overview

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

• Device AirBand
  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 phys
• Device uninflated AirBand
  Uninflated AirBand will be used as the control intervention during the session in which BFR is not performed

Primary outcome measures

• Change in Leukocyte metabolic gene expression [Time frame: Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise]
• Change in leukocyte substrate preference [Time frame: Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise]
• Change in amino acids concentrations [Time frame: Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise]
• Change in glucose concentrations [Time frame: Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise]
• Change in lactate concentrations [Time frame: Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise]
• Change in fatty acid concentrations [Time frame: Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise]
• Change in insulin concentrations [Time frame: Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise]
• Change in glucagon concentrations [Time frame: Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise]
• Change in catecholamines concentrations [Time frame: Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise]

Secondary outcome measures (3)

• Whether a baseline immunometabolic blueprint predicts the immunometabolic response to resistance training or to BFR. [Time frame: 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. [Time frame: Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise]
• Change in creatine kinase [Time frame: Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Single blind

Primary purpose

Basic science

Study locations

United States · 2 centers

• Yale New Haven Hospital — Milford
• Gaylord Outpatient Physical Therapy North Haven Clinic — North Haven

Identifiers

NCT: NCT05012982 · 2000030152

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗