Evaluation of Botulinum Toxin Type A for Preventing Shoulder Deformity in Infants with Obstetrical Brachial Plexus Palsy: A Randomized Controlled Trial

The primary objective of this study is to evaluate the **efficacy** of botulinum toxin injections into the shoulder internal rotator muscles at 12 months of age in preventing the worsening of posterior glenohumeral joint subluxation in infants aged 11 to 18 months with **obstetrical brachial plexus palsy**. This is clinically relevant as it aims to address a common complication associated with this condition, potentially improving long-term joint function and reducing the need for surgical interventions.

Secondary objectives include:

• Evaluating the efficacy of botulinum toxin injections versus Sham in preventing worsening of glenoid retroversion and three-dimensional deformity.
• Assessing the effect of injections versus Sham in improving active and passive joint amplitudes and function.
• Confirming the good clinical tolerance of this treatment.
• Assessing the impact of injections on the targeted muscles in terms of trophicity, fibrous and fatty infiltration, and muscular balance in the shoulder with POPB.
• Determining whether this treatment will eventually lead to a change in the frequency and type of surgical management.

The clinical trial focused on evaluating the efficacy of botulinum toxin injections in infants with **Obstetrical Brachial Plexus Palsy**. The study population comprised male and female infants aged between 11 and 18 months. The trial included participants who presented with unilateral palsy and specific risk factors for posterior subluxation of the humeral head, such as a limitation of passive joint amplitude in external rotation or an Active Movement Scale score below 6 for certain movements. The trial did not involve a vulnerable population, and the consent of adult parents was required for participation. The sponsor did not provide information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the **efficacy** and safety of early intramuscular **botulinum toxin type A** injections in preventing shoulder deformity in infants with **obstetrical brachial plexus palsy**. This study is a randomized, double-blind, multicenter controlled trial. The trial aims to assess the impact of botulinum toxin injections into the shoulder internal rotator muscles at 12 months of age, compared to a sham group, in preventing the worsening of posterior glenohumeral joint subluxation in infants aged between 11 and 18 months. The trial is expected to conclude by June 2025, with recruitment having commenced in May 2018.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, presence of unilateral obstetrical brachial plexus palsy, and specific risk factors for posterior subluxation of the humeral head. Following the screening, eligible participants will be randomized to receive either the active treatment or placebo. The primary endpoint is the evolution of the percentage of posterior migration of the humeral head, measured via MRI, from 11 months to 18 months of age. Secondary endpoints include assessments of 2D glenoid evolution, changes in passive joint amplitudes, and the evolution of the Active Movement Scale (AMS), among others.

Participants are expected to be involved in the study for a maximum treatment period of one month, with follow-up visits scheduled to monitor progress and collect data on the primary and secondary endpoints. The end-of-study visit will occur at 18 months of age, six months post-injection, to evaluate the long-term effects of the treatment. Conditions that may lead to early termination from the study include withdrawal of consent by the parents or the occurrence of serious adverse events. The trial is conducted under strict adherence to ethical guidelines, ensuring the safety and well-being of all participants throughout the study duration.

The clinical trial involves the administration of **BOTOX 100 Unità Allergan Polvere per soluzione iniettabile**, which contains the active substance **botulinum toxin type A**. This experimental medication is provided in the form of a **solution for injection**. The route of administration is **intramuscular injection**, specifically targeting the shoulder internal rotator muscles. The dosage is calculated based on the participant's weight, with a maximum daily and total dose of 8 IU/Kg. The treatment period is limited to a maximum of 1 day. The primary objective is to assess the efficacy of this intervention in preventing the worsening of posterior glenohumeral joint subluxation in infants with obstetric brachial plexus palsy.

In addition to the experimental treatment, the study utilizes **sodium chloride** as a placebo. This non-experimental treatment is provided in the form of a **solution for skin-prick test**. The route of administration is categorized as **other use**, and it serves as a control to compare against the effects of the botulinum toxin injections. Sodium chloride is an isotonic liquid with no active pharmacological effect in the context of this trial. The placebo is used to maintain the double-blind nature of the study, ensuring that neither the participants nor the investigators are aware of the treatment assignments.

The efficacy of botulinum toxin injections in preventing shoulder deformity in infants with obstetric brachial plexus palsy will be assessed through a series of primary and secondary endpoints. The primary endpoint involves the evaluation of the evolution of the percentage of posterior migration of the humeral head, measured using MRI on an axial section. This measurement will be taken at 11 months of age, prior to the botulinum toxin injection, and again at 18 months, six months post-injection.

Secondary endpoints include several MRI-based assessments: the 2D glenoid evolution on an axial slice, the evolution of the glenoid version, and three-dimensional humeral head migration. Additionally, changes in passive joint amplitudes and the evolution of the Active Movement Scale (AMS) will be evaluated. The progression of the mini-Assistive Hand Assessment (mini-AHA) score will also be monitored. Furthermore, the study will assess the number of non-serious and serious adverse events, as well as the trophicity (muscle volume) and fatty infiltration of injected muscles, including the supraspinatus, infraspinatus, lesser round, subscapularis, greater round, pectoralis major, deltoid, and greater dorsalis.

Data collection will occur at specified timepoints, with MRI assessments conducted at 11 and 18 months of age. The AMS and mini-AHA scores will be evaluated to track functional improvements. The study will also record surgical management of the children in each group post-study during routine clinical follow-up up to the 10th year of life, after the blind has been lifted. These comprehensive assessments will provide a robust evaluation of the efficacy of botulinum toxin injections in this patient population.