UltraSound-Guided Versus Non-Ultrasound-Guided Botulinum Toxin Injections in Cervical Dystonia [CUSTODY] (CUSTODY)

A Randomised, Cross-over, Double-blind, Sham-Controlled Superiority Trial of UltraSound-Guided Versus Non-Ultrasound-Guided Botulinum TOxin Injections in Cervical DYstonia

Cervical dystonia is a condition that causes the neck muscles to tighten or spasm, leading to abnormal head positions and pain.

The main questions it aims to answer are:

• Do ultrasound-guided BoNT injections improve quality of life more than injections without ultrasound?
• Are ultrasound-guided injections as safe as injections without ultrasound?

Researchers will compare:

• BoNT injections with ultrasound guidance
• BoNT injections without ultrasound guidance (based only on body landmarks)

Participants will:

• Receive both types of injections during the study (one first, then the other)
• Complete questionnaires about quality of life, movement, pain, and mood
• Attend follow-up visits over about 8 months About 37 adults with cervical dystonia will take part. The study will take place at the Fondazione IRCCS Istituto Neurologico Carlo Besta in Milan, Italy.

Study Overview

• Status: Recruiting
• Conditions: Idiopathic Cervical Dystonia
• Intervention / Treatment: Procedure: Ultrasound-guided botulinum toxin injection; Procedure: Non-ultrasound-guided botulinum toxin injection

Detailed Description

Cervical dystonia (CD) is the most common type of focal dystonia and is characterised by sustained or intermittent involuntary contractions of the neck muscles. These contractions lead to abnormal head postures and movements, frequently associated with pain and tremor, and have a major impact on quality of life.

The established treatment for CD is repeated intramuscular injections of botulinum toxin type A (BoNT-A), usually every 12 to 16 weeks. BoNT-A blocks acetylcholine release at the neuromuscular junction, producing a temporary and reversible chemodenervation of the target muscle. Clinical benefit generally appears within a few days, peaks after 2 to 4 weeks, and gradually wears off after 3 to 4 months, requiring repeated injections. Although this therapy is effective and safe, its clinical success largely depends on the accuracy of muscle targeting. Suboptimal precision in injections can lead to unsatisfactory outcomes, persistence of symptoms, or treatment discontinuation.

Several approaches are used in clinical practice to guide injections. The conventional method relies on palpation and anatomical landmarks, is widely available, and requires limited resources. However, it depends heavily on the injector's experience and may result in inaccurate targeting. Ultrasound (US) guidance, on the other hand, allows direct, real-time visualisation of the cervical muscles and adjacent structures. This technique may increase accuracy, optimise toxin distribution, and lower the risk of misplaced injections and adverse events.

Cadaveric studies have demonstrated higher accuracy of US-guided injections compared with landmark-based methods, and preliminary clinical studies suggest that US guidance may improve outcomes. However, these studies have been limited by small sample sizes, lack of randomisation, or non-blinded assessments. Robust evidence from randomised controlled trials is still lacking, and therefore the clinical superiority of US guided injectionsance remains uncertain.

US-guided injections also require additional equipment, time, and operator training. This may limit their widespread adoption in routine clinical practice unless a clear advantage over landmark-based injections is demonstrated. Addressing this knowledge gap is essential to inform clinical decisions and optimise the management of CD.

The present study has been designed to evaluate the impact of US-guided BoNT-A injections compared with injections based only on anatomical landmarks in adults with idiopathic CD. The primary objective is to determine whether US guidance provides superior improvements in quality of life. Secondary objectives include assessing the effects of the two techniques on motor and non-motor symptoms, as well as comparing their safety.

A total of approximately 37 participants with idiopathic cervical dystonia and a documented good response to prior BoNT-A therapy will be recruited at the Fondazione IRCCS Istituto Neurologico Carlo Besta in Milan, Italy. Each participant will undergo two treatment cycles, one with US guidance and one without, in randomised order. The duration of participation for each individual will be about 8 months. By directly comparing two widely used approaches, this trial will provide high-quality evidence to guide clinical practice and improve care for people with cervical dystonia.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Roberto Eleopra, MD; Phone Number: + 39 02.2394; Email: roberto.eleopra@istituto-besta.it

Study Locations

• Italy
  • Milan, Italy
    • Recruiting
    • Fondazione IRCCS Istituto Neurologico Carlo Besta
    • Contact: Valentina Leta, MD; Phone Number: + 39 02.2394; Email: valentina.leta@istituto-besta.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Minimum age 18 years old
• Clinical diagnosis of Idiopathic Cervical Dystonia
• On a stable dose of other medications (if any) used for focal dystonia treatment (e.g. anticholinergics and benzodiazepines) for at least 3 months prior to screening and expected to be maintained throughout the study
• Treatment non-naïve to BoNT type A therapy for CD
• At least 4 months have passed between the last BoNT injection at screening
• Good clinical response to previous BoNT injections, on stable dosing and treatment scheme
• Informed Consent as documented by signature.
• Ability to perform study requirements (to attend assessment and treatments)

Exclusion Criteria:

• Diagnosis of other types of Cervical Dystonia (Inherited and Acquired)

  • Concomitant diagnosis of diseases that contraindicate the use of botulinum toxin, such as myasthenia gravis
  • Known hypersensitivity or allergy to Botulinum-A Toxin
  • Women who are pregnant or breast feeding
  • Intention to become pregnant during the study
  • Lack of safe contraception
  • Other clinically significant and unstable concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease, etc.).
  • Inability to follow the procedures of the study, e.g., due to language problems, psychological disorders, dementia, etc. of the participant
  • Participation in another study with investigational drug within the 30 days preceding and during the present study
  • Previous enrolment into the current study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ultrasound-Guided BoNT Injections; Participants receive botulinum toxin type A injections into cervical muscles using real-time ultrasound guidance to visualise target muscles and surrounding structures	Procedure: Ultrasound-guided botulinum toxin injection; Botulinum toxin type A is injected into dystonic cervical muscles under real-time ultrasound guidance, allowing visualisation of target muscles and adjacent structures. Injections are performed according to standard clinical practice with a stable dose and scheme; Procedure: Non-ultrasound-guided botulinum toxin injection; Botulinum toxin type A is injected into dystonic cervical muscles using anatomical landmarks, without ultrasound guidance. To maintain blinding, the ultrasound device is present in all procedures, but the screen is turned off in this arm. Injections are performed according to standard clinical practice with a stable dose and scheme
Sham Comparator: Non-Ultrasound-Guided BoNT Injections; Participants receive botulinum toxin type A injections into cervical muscles using anatomical landmarks, without ultrasound guidance. The ultrasound device is present but the screen is turned off to maintain blinding.	Procedure: Ultrasound-guided botulinum toxin injection; Botulinum toxin type A is injected into dystonic cervical muscles under real-time ultrasound guidance, allowing visualisation of target muscles and adjacent structures. Injections are performed according to standard clinical practice with a stable dose and scheme; Procedure: Non-ultrasound-guided botulinum toxin injection; Botulinum toxin type A is injected into dystonic cervical muscles using anatomical landmarks, without ultrasound guidance. To maintain blinding, the ultrasound device is present in all procedures, but the screen is turned off in this arm. Injections are performed according to standard clinical practice with a stable dose and scheme

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cervical Dystonia Impact Profile-58 (CDIP-58) score	Total score on the Cervical Dystonia Impact Profile (CDIP-58), a patient-reported outcome measure of quality of life in cervical dystonia. Score range: 0-100, with higher scores indicating greater impact on quality of life (worse outcome).	6 weeks (±2 weeks) after each treatment, during both periods of the cross-over desig

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of adverse events	Number and type of any adverse events reported during both crossover periods. Safety will be assessed by comparing the frequency of adverse events between the two injection techniques.	From baseline to 16 weeks (±2 weeks) after each treatment, during both periods of the cross-over design.
Change in Toronto Western Spasmodic Torticollis Rating Scale - 2 (TWSTRS-2)	Total score on the Toronto Western Spasmodic Torticollis Rating Scale, 2nd edition (TWSTRS-2), a clinician-rated scale assessing severity, disability, and pain in cervical dystonia. Score range: 0-100, with higher scores indicating greater severity, disability, or pain (worse outcome).	6 weeks (±2 weeks) after each treatment, during both periods of the cross-over design.
Change in Patient Global Impression - Change (PGI-C) score	Score on the Patient Global Impression of Change (PGI-C), a 7-point patient-reported scale reflecting the patient's impression of improvement. Score range: 1-7, with higher scores indicating greater improvement (better outcome).	6 weeks (±2 weeks) after each treatment, during both periods of the cross-over design.
Change in Psychiatric Screening Tool (TWSTRS-PSYCH) score	The TWSTRS-PSYCH assesses psychiatric comorbidity associated with cervical dystonia. The total score ranges from [inserire range corretto, es. 0-X], with higher scores indicating greater psychiatric symptom severity (worse outcome).	6 weeks (±2 weeks) after each treatment, during both periods of the cross-over design.
Change in Hospital Anxiety and Depression Scale (HADS) score	The HADS is a 14-item self-administered questionnaire assessing anxiety and depressive symptoms. The total score ranges from 0 to 42, with higher scores indicating greater anxiety and depressive symptom severity (worse outcome). Each subscale (HADS-A and HADS-D) ranges from 0 to 21, with higher scores indicating worse symptoms.	6 weeks (±2 weeks) after each treatment, during both periods of the cross-over design.
Change in Pain Numerical Rating Scale (NRS) score	Pain intensity is assessed using the Numeric Rating Scale (NRS), which ranges from 0 (no pain) to 10 (worst imaginable pain). The outcome measure is the change in NRS score from baseline to 6 weeks after each injection in both crossover periods. Higher scores indicate greater pain severity (worse outcome).	6 weeks (±2 weeks) after each treatment, during both periods of the cross-over design.
Change in Clinical Global Impression - Change (CGI-C) score	The CGI-C is a 7-point clinician-rated scale assessing overall clinical improvement compared to baseline. Scores range from: = Very much improved; = Much improved; = Minimally improved; = No change; = Minimally worse; = Much worse; = Very much worse Lower scores indicate greater clinical improvement (better outcome).	6 weeks (±2 weeks) after each treatment, during both periods of the cross-over design.

Collaborators and Investigators

• Sponsor: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta

Publications and helpful links

General Publications

• Albanese A, Bhatia K, Bressman SB, Delong MR, Fahn S, Fung VS, Hallett M, Jankovic J, Jinnah HA, Klein C, Lang AE, Mink JW, Teller JK. Phenomenology and classification of dystonia: a consensus update. Mov Disord. 2013 Jun 15;28(7):863-73. doi: 10.1002/mds.25475. Epub 2013 May 6.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 14, 2025
• First Posted (Actual): November 18, 2025

Study Record Updates

• Last Update Posted (Actual): February 13, 2026
• Last Update Submitted That Met QC Criteria: February 11, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Quality of life; Botulinum toxin; Non-motor symptoms; Motor symptoms; Cervical dystonia; Idiopathic cervical dystonia; BoNT injections; Ultrasound-guided injections; Anatomical landmark
• Additional Relevant MeSH Terms: Neurologic Manifestations; Dyskinesias; Dystonia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Torticollis
• Other Study ID Numbers: CUSTODY

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No