A Multimodal Approach to Cervical Dystonia Treatment With Association of Botulinum Toxin and Motor Learning Techniques (SPRInt)

• ClinicalTrials.gov Identifier: NCT03247868
• Recruitment Status: Unknown
• First Posted: August 14, 2017
• Last Update Posted: August 14, 2017
• Sponsor: Fondazione Don Carlo Gnocchi Onlus
• Information provided by (Responsible Party): Fondazione Don Carlo Gnocchi Onlus

Tracking Information

• First Submitted Date: July 27, 2017
• First Posted Date: August 14, 2017
• Last Update Posted Date: August 14, 2017
• Study Start Date: March 16, 2016
• Estimated Primary Completion Date: March 28, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 11, 2017)

Dystonia phenomenology improvement [ Time Frame: every six weeks during six months time ]

a clinical assessment of dystonia will be conducted at each study visit using TWSTRS

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: August 11, 2017)

• quality of life [ Time Frame: every six weeks during six months time ]
  a clinical assessment of dystonia severity will be conducted at each study visit using quality of life scale (EQ5D5L)
• brain plasticity [ Time Frame: every six weeks during six months time ]
  study of functional connectivity using functional magnetic resonance
• depression [ Time Frame: every six weeks during six months time ]
  depression scale (BECK)
• anxiety [ Time Frame: every six weeks during six months time ]
  anxiety scale (ZUNG)
• structural grey matter plasticity [ Time Frame: every six weeks during six months time ]
  brain study of morphometry using functional magnetic resonance
• structural white matter plasticity [ Time Frame: every six weeks during six months time ]
  tractography of brain areas using functional magnetic resonance
• kinematic assessment of dystonia severity [ Time Frame: every six weeks during six months time ]
  visit with optoelectronic system

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Multimodal Approach to Cervical Dystonia Treatment With Association of Botulinum Toxin and Motor Learning Techniques
• Official Title: Multimodal Treatment of Cervical Dystonia With Botulinum Toxin Injections Associated With a Sensory-motor Perceptive Rehabilitation Integrated Approach (SPRInt) Based on Motor Learning Techniques
• Brief Summary: the aim of this study protocol is to describe, using a longitudinal study, a multimodal approach of treatment of cervical dystonia with botulinum toxin (BoNTA) and a new rehabilitation protocol named SPRInt (Sensory-motor perceptive rehabilitation integrated) approach based on motor learning techniques and spatial rehabilitation.

Detailed Description

Longitudinal study utilizing a multimodal treatment protocol developing in six months time:

Phase 1 : BoNTA injections localized in dystonic cervical muscles with EMG/US guides performed after polygraphy and kinematic analysis of cervical region Times: T0: pre treatment; T1: 6 weeks after T0 considered BoNTA pharmacological peak effect; T2: 12 weeks after T0 considered from guidelines and pharmaceutical data sheet the lowest BoNTA effect.

Phase 2: BoNTA performed in the same way of Phase 1 associated to SPRInt protocol Times: T2: before combination of BoNTA and rehabilitation treatment (18 sessions of 45 minutes three times a week); T3: 6 weeks after T2 considered BoNTA pharmacological peak effect and the end of SPRInt protocol; T4: 12 weeks after T2 considered from guidelines and pharmaceutical data sheet the lowest BoNTA effect and follow up of SPRInt-consolidation.

The SPRInt approach aims are to improve body perception, posture and movement quality and to restore body axis by using specific sensory feedbacks, both intrinsic (IFB) and extrinsic (EFB), and motor exercises (ME) with specific rhythmic temporal structure.The ME can be focused on different body parts (eyes, head, neck, trunk, arm) and involve different spatial planes (frontal, sagittal, horizontal, multiplanar).

The exercises can be performed with eyes closed and with an external passive motor leading in order to improve proprioception and facilitate sensory integration by excluding visual or verbal information that can be misleading for the patient. The ability to perceive and integrate intrinsic feedback is the fundamental element to create mental image that define body scheme and motor behaviour.

The extrinsic feedback can be continuous or discontinuous (on-off timing) and gives the patient information about the performance or result by positive or negative reinforcement; this process can be important to motivate and empower the patient in reaching new skills.

The final goal for the patient is to reinforce and retain the informations collected with working memory and then stored with the consolidation process which ends in learning new skills (ie rescue postural axis) and improving motor tasks (ie move the head in the opposite position).

At each time point these test are performed:

• CLINICAL SCALES i. Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)

  1. Severity
  2. Disability
  3. Pain ii. Quality of life iii. Depression Beck Scale iv. Zung Self Rating Anxiety Scale v. Rey Test to test visuo spatial abilities
• MOVEMENT ANALYSIS and KINEMATIC AND EMG MAPPING of cervical region ( head and neck)
• FUNCTIONAL MAGNETIC RESONANCE BRAIN STUDY to perform brain measurements of functional connectivity (resting state-Default Mode Network), morphometry (volume, area, cortical thickness, cortical curvature, node degree) and tractography.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cervical Dystonia,Primary

Intervention

Combination Product: Botulinum Toxin+SPRInt

Botulinum toxin injections in association with rehabilitative approach to cervical dystonia (SPRInt)

Study Arms

Experimental: Botulinum toxin+SPRInt protocol

patients affected by cervical dystonia receive botulinum toxin treatment (EMG-US guided injections in dystonic muscles) for two times at T0 and T2; after T2 patients are treated also with SPRInt rehabilitation protocol based on motor learning techniques.

Intervention: Combination Product: Botulinum Toxin+SPRInt

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. Review.
• Boccagni C, Carpaneto J, Micera S, Bagnato S, Galardi G. Motion analysis in cervical dystonia. Neurol Sci. 2008 Dec;29(6):375-81. doi: 10.1007/s10072-008-1033-z. Epub 2008 Nov 29.
• Walter U, Dressler D. Ultrasound-guided botulinum toxin injections in neurology: technique, indications and future perspectives. Expert Rev Neurother. 2014 Aug;14(8):923-36. doi: 10.1586/14737175.2014.936387. Epub 2014 Jul 21. Review.
• Prudente CN, Hess EJ, Jinnah HA. Dystonia as a network disorder: what is the role of the cerebellum? Neuroscience. 2014 Feb 28;260:23-35. doi: 10.1016/j.neuroscience.2013.11.062. Epub 2013 Dec 11. Review.
• Delnooz CC, Pasman JW, van de Warrenburg BP. Dynamic cortical gray matter volume changes after botulinum toxin in cervical dystonia. Neurobiol Dis. 2015 Jan;73:327-33. doi: 10.1016/j.nbd.2014.10.013. Epub 2014 Oct 28.
• Delnooz CC, Pasman JW, Beckmann CF, van de Warrenburg BP. Task-free functional MRI in cervical dystonia reveals multi-network changes that partially normalize with botulinum toxin. PLoS One. 2013 May 1;8(5):e62877. doi: 10.1371/journal.pone.0062877. Print 2013.
• De Pauw J, Van der Velden K, Meirte J, Van Daele U, Truijen S, Cras P, Mercelis R, De Hertogh W. The effectiveness of physiotherapy for cervical dystonia: a systematic literature review. J Neurol. 2014 Oct;261(10):1857-65. doi: 10.1007/s00415-013-7220-8. Epub 2014 Jan 12. Review.
• van den Dool J, Visser B, Koelman JH, Engelbert RH, Tijssen MA. Cervical dystonia: effectiveness of a standardized physical therapy program; study design and protocol of a single blind randomized controlled trial. BMC Neurol. 2013 Jul 15;13:85. doi: 10.1186/1471-2377-13-85.
• Simpson DM, Hallett M, Ashman EJ, Comella CL, Green MW, Gronseth GS, Armstrong MJ, Gloss D, Potrebic S, Jankovic J, Karp BP, Naumann M, So YT, Yablon SA. Practice guideline update summary: Botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2016 May 10;86(19):1818-26. doi: 10.1212/WNL.0000000000002560. Epub 2016 Apr 18.
• Currà A, Trompetto C, Abbruzzese G, Berardelli A. Central effects of botulinum toxin type A: evidence and supposition. Mov Disord. 2004 Mar;19 Suppl 8:S60-4. Review.
• Kitago T, Krakauer JW. Motor learning principles for neurorehabilitation. Handb Clin Neurol. 2013;110:93-103. doi: 10.1016/B978-0-444-52901-5.00008-3. Review.
• Castagna A, Caronni A, Crippa A, Sciumè L, Giacobbi G, Corrini C, Montesano A, Ramella M. Sensorimotor Perceptive Rehabilitation Integrated (SPRInt) program: exercises with augmented movement feedback associated to botulinum neurotoxin in idiopathic cervical dystonia-an observational study. Neurol Sci. 2020 Jan;41(1):131-138. doi: 10.1007/s10072-019-04061-5. Epub 2019 Sep 2.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: August 11, 2017): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 30, 2018
• Estimated Primary Completion Date: March 28, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• more than 18 yo
• diagnosis of idiopathic cervical dystonia
• disease duration more than 6 months

Exclusion Criteria:

• diagnosis of secondary dystonia on previously performed neuroimaging data (ie structural lesion of cervical spine, vascular or traumatic brain injuries)
• history of neuroleptic drug treatment (antidopaminergic drugs)
• associated neurological illness
• botulinum toxin treatment in the 3 previous months before recruitment
• head tremor without dystonic posturing

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy

Administrative Information

• NCT Number: NCT03247868
• Other Study ID Numbers: SPRIntFdG
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Fondazione Don Carlo Gnocchi Onlus
• Study Sponsor: Fondazione Don Carlo Gnocchi Onlus
• Collaborators: Not Provided

Investigators

• Principal Investigator: Anna Castagna, MD; IRCCS Fondazione Don Gnocchi

• PRS Account: Fondazione Don Carlo Gnocchi Onlus
• Verification Date: July 2017