Skip to main content
OpenTrials
Recruiting

NCT Number: NCT05012982

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

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.

Recruiting

Interested in participating?

Request Info

Key information

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Yale New Haven Hospital, Milford, Connecticut, United States

Loading trial locations.

About this study

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

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

AirBand

Device

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.

uninflated AirBand

Device

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

Primary outcomes

  1. Change in Leukocyte metabolic gene expression

    Time frame: 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.

  2. Change in leukocyte substrate preference

    Time frame: 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.

  3. Change in amino acids concentrations

    Time frame: 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).

  4. Change in glucose concentrations

    Time frame: 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.

  5. Change in lactate concentrations

    Time frame: 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.

  6. Change in fatty acid concentrations

    Time frame: 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.

  7. Change in insulin concentrations

    Time frame: 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.

  8. Change in glucagon concentrations

    Time frame: 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.

  9. Change in catecholamines concentrations

    Time frame: 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.

Secondary outcomes

  1. 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

    Correlation between Outcomes 1-9 at 0, 30 and 60 minutes after training, to Outcomes 1-9 before training

  2. 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

    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.

  3. Change in creatine kinase

    Time frame: Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise

    Creatine kinase concentration

Study contacts

Contact information is provided by the study sponsor or research team.

Andin Fosam, BS

CONTACT

[email protected]

609-578-7713

Rachel Perry, PhD

CONTACT

[email protected]

203-506-5179

Sponsors and collaborators

Lead sponsor

Yale University

Other

Registry information

Official study title

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

Important dates

Study start
2023
Primary completion
2026
Study completion
2026
First posted
Aug 19, 2021
Registry last updated
Dec 3, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.