Evaluation of Clostridium Botulinum Neurotoxin Type A in Degenerative Rotator Cuff Tendinopathy: A Randomized, Placebo-Controlled Trial

The primary objective of this study is to evaluate the effectiveness of **botulinum toxin** in the treatment of degenerative tendinopathy of the rotator cuff of the shoulder. This will be assessed at one month using the Shoulder Pain and Disability Index (SPADI) total score. The clinical relevance of this objective lies in determining the potential of botulinum toxin as a therapeutic option for improving shoulder function and reducing pain in patients with this condition.

Secondary objectives include:

• Evaluating the effectiveness of botulinum toxin based on the total SPADI score at 3 months.
• Assessing the effectiveness based on SPADI sub-scores for pain and functional limitation at 3 months.
• Evaluating perceived overall improvement using the Visual Analog Scale (VAS) from 0 to 100 at 1 and 3 months.
• Assessing the effectiveness based on painkiller medication consumption over the 3 months of follow-up.
• Evaluating the acceptability of treatment by VAS from 0 to 100 at 1 month and 3 months.
• Assessing the tolerance of botulinum toxin at 1 week by collecting adverse effects such as muscle weakness, difficulty swallowing, speaking, dyspnea, and allergic reactions.

The clinical trial focuses on individuals diagnosed with **degenerative shoulder rotator cuff tendinopathy**. The study population includes both male and female participants, with an age range starting from 40 years and above. Participants are required to be in general good health, with specific criteria such as a pain duration of more than one month and a pain intensity of at least 40 out of 100 on the visual analog scale. The trial does not involve a vulnerable population. Participants must have a **SPADI** score of 30 or higher and must have undergone an ultrasound within 30 days showing supraspinatus tendinopathy. Lifestyle considerations include the requirement for women of childbearing potential to use effective contraception. The sponsor has not provided information regarding the total number of participants in the trial. Selection criteria also include the ability to attend scheduled visits and provide informed consent. Participants must have stable pain medication usage for at least 30 days prior to enrollment. The trial does not focus on any specific lifestyle habits such as diet or physical activity.

The clinical trial is designed to evaluate the effectiveness of **botulinum toxin** in the treatment of degenerative shoulder rotator cuff tendinopathy. This study is a randomized, double-blind, controlled trial, involving the administration of XEOMIN 100 units, a **solution for injection**, and a placebo. The trial is set to span a duration from January 20, 2023, to January 20, 2027, with the primary endpoint being the total Shoulder Pain and Disability Index (SPADI) score at one month. Secondary endpoints include the total SPADI score at three months, SPADI sub-scores at three months, perceived overall improvement by visual analog scale (VAS) at one and three months, painkiller medication consumption over the three months of follow-up, and acceptability of treatment by VAS from 0 to 100 at one month and three months.

Participants will undergo a sequence of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age over 40 years, pain duration greater than one month, and a SPADI score of at least 30/100. The inclusion visit will also ensure that pain medication has remained unchanged within 30 days prior to enrollment and that an ultrasound within 30 days shows supraspinatus tendinopathy. Following the screening, participants will be randomized to receive either the active treatment or placebo via **intramuscular injection**. Follow-up visits will be conducted at one month and three months to assess the primary and secondary endpoints. The end-of-study visit will mark the conclusion of the participant's involvement in the trial.

The expected length of participant involvement is approximately three months, with conditions for early termination including non-compliance with the study protocol, withdrawal of consent, or adverse events that necessitate discontinuation. Participants are required to use effective contraception if of childbearing potential and must have a negative urine test if applicable. The trial is conducted under the auspices of Merz Pharmaceuticals GmbH, with the investigational product being XEOMIN 100 units, and the placebo being a powder for injection. The trial is categorized as Phase 4, with a focus on evaluating the therapeutic efficacy and safety of the intervention in a real-world setting.

The clinical trial involves the administration of **XEOMIN**, a pharmaceutical product containing **Clostridium botulinum neurotoxin type A (150kD), free of complexing proteins**. XEOMIN is provided in the form of a powder for solution for injection, specifically designed for intramuscular administration. The dosage for this trial is set at 100 international units (IU) per administration, with a maximum daily and total dose of 100 IU. The treatment period is limited to one month. XEOMIN is manufactured by Merz Pharmaceuticals GmbH and is classified under the ATC code M03AX01, which corresponds to botulinum toxin. The administration of XEOMIN will be monitored to ensure participant compliance with the dosing schedule.

In addition to the experimental treatment, a placebo is utilized in this study. The placebo is designed to mimic the appearance and administration route of XEOMIN, being a powder for injection. However, it contains no active substance. The placebo serves as a comparator to evaluate the effectiveness of XEOMIN in treating degenerative tendinopathy of the rotator cuff of the shoulder. The placebo is administered following the same schedule and route as the experimental medication to maintain the study's integrity and ensure blinding.

Efficacy in the clinical trial titled "DEROTOX: DEgenerative ROtator cuff disease and botulinum TOXin" will be assessed using the Shoulder Pain And Disability Index (SPADI) score. The primary endpoint is the total SPADI score at one month. Secondary endpoints include the total SPADI score at three months, SPADI sub-scores at three months, perceived overall improvement measured by the Visual Analog Scale (VAS) at one and three months, painkiller medication consumption over the three months of follow-up, and the acceptability of treatment assessed by VAS from 0 to 100 at one month and three months.

The SPADI score is a validated tool used to measure pain and disability associated with shoulder conditions. The VAS is a commonly used instrument for assessing perceived improvement and treatment acceptability. Efficacy parameters will be collected at specified timepoints, including one month and three months post-treatment. The analysis will focus on changes in SPADI scores and VAS ratings to determine the effectiveness of **botulinum toxin** in treating degenerative tendinopathy of the rotator cuff.