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

NCT05012982 | Recruiting DMC

• 1 other identifier: 2000030152
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

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.

Conditions

Anterior Cruciate Ligament Reconstruction

Keywords

AirBand

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (3)

• 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

• 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

• Change in creatine kinase

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

Study Arms (2)

AirBand followed by uninflated AirBand

EXPERIMENTAL

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; Device: uninflated AirBand

Uninflated Airbnd followed by AirBand

EXPERIMENTAL

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; Device: uninflated AirBand

Interventions

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.

AirBand followed by uninflated AirBand; Uninflated Airbnd followed by AirBand

uninflated AirBand DEVICE

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

AirBand followed by uninflated AirBand; Uninflated Airbnd followed by AirBand

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead

Study Sites (2)

Yale New Haven Hospital

Milford, Connecticut, 06461, United States

RECRUITING

Gaylord Outpatient Physical Therapy North Haven Clinic

North Haven, Connecticut, 06473, United States

RECRUITING

Study Officials

• Rachel Perry, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rachel Perry, PhD

CONTACT

203-506-5179; rachel.perry@yale.edu

Andin Fosam, BS

CONTACT

609-578-7713; andin.fosam@yale.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2021
• First Posted: August 19, 2021
• Study Start: February 16, 2023
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: December 3, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)