NCT04837417: AQUARIUS

Deficit in Quadriceps Voluntary Activation After Anterior Cruciate Ligament Reconstruction: Roles of the "Learned Non-use" Paradigm and the Interhemispheric Inhibition

Completed Last updated 18 November 2025

What this trial tests

trial testing Pathologic group in Anterior Cruciate Ligament Injuries in 10 participants. Completed in 31 December 2024.

Timeline

14 July 2021

Primary endpoint
31 December 2024

31 December 2024

Quick facts

Lead sponsor	Istituto Auxologico Italiano
Status	Completed
Study type	OBSERVATIONAL
Enrollment	10
Start date	14 July 2021
Primary completion	31 December 2024
Estimated completion	31 December 2024
Sites	2 locations across Italy

Drugs / interventions tested

• Pathologic group

Conditions studied

• Anterior Cruciate Ligament Injuries — all drugs for Anterior Cruciate Ligament Injuries →

Sponsor

Istituto Auxologico Italiano — full company profile →

Who can join

Adults 18 to 35, male only, with Anterior Cruciate Ligament Injuries. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Anterior cruciate ligament (ACL) tear is mainly caused by sport injuries. 40% of injuries are attributed to noncontact mechanisms involving pivoting. Regaining quadriceps strength is a primary focus of patients pursuing a rehabilitation program after ACL reconstruction (ACLR). Unfortunately, despite rehabilitation programs aimed at reversing this muscle weakness, quadriceps strength deficits may persist for years. Moreover, this deficit leads to increased risk of sustaining another knee injury, and increased risk for developing posttraumatic osteoarthritis. At present, neither the optimal rehabilitative program nor the clinical and instrumental parameters to take into account at the time of return to activity have reached a consensus among clinicians.

The investigators hypothesize that:

* a persistent deficit in voluntary activation, that is an inability to achieve complete activation of a muscle, is present after ACLR.
* this deficit in voluntary activation is associated with a phenomenon of "learned/acquired non-use" both in balance and during gait. This phenomenon will be demonstrated by investigating asymmetries in the recruitment of the injured lower limb in balance tests and during gait.
* the "learned/acquired non-use" paradigm is associated to asymmetries in the hemispheric cortical activity. This phenomenon will be investigated through transcranial magnetic stimulation.

The primary endpoint is the demonstration that the quadriceps muscle weakness after ACLR may represent a case of "learned non-use". This behaviour looks automatic and unconscious, so that the adjective "acquired" seems preferable to "learned". It consists of the under recruitment of the impaired side, once healed, as a form of unconscious protection, which is adopted when the contralateral side may carry out the function.

The secondary outcome is the investigation of the correlation among the deficits in voluntary activation, in balance tests, during gait, and in the neurophysiologic trials, with the clinical conditions of the patients.

It is expected that the injured lower limb show a deficit in the activation of the quadriceps muscle with respect to the contralateral one and with respect to normative data. The impaired limb will present lower recruitment in balance tests and a deficit in power production during gait.

The contralesional hemisphere will demonstrate higher interhemispheric inhibition, lower short-interval intracortical inhibition (SICI) and higher short-interval intracortical facilitation (SICF) with respect to the ipsilesional hemisphere.

The evidence for an asymmetry between the two lower limbs would support the hypothesis that the "acquired non-use" paradigm has a role in the deficits following ACL lesions and that it is unspecific across asymmetric impairments, and independent of the underlying disease.

Results from the present study will allow:

* the identification of clinical and instrumental criteria to guide the return-to-sport decision following ACLR.
* the estimate of the sample size for future experimental protocols and new rehabilitative programs.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Anterior cruciate ligament reconstruction is associated with increased corticospinal excitability and rate of force development.
   Scarano S, Caronni A, Menon A, Rota V, et al · · 2026 · PMID 41656237 · DOI 10.1186/s13102-026-01577-0