Clinical trial NCT04437056: Nerve Transfers in Post-stroke Spasticity
Official title: Outcome Measurements After Cognitive Nerve Transfers to Spastic Muscles in Stroke Patients
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Spasticity as Sequela of Stroke
Nerve Transfers
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
Collaborators: name: Imperial College London
name: Shirley Ryan AbilityLab
First posted: 2020-06-18
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Stroke is nowadays a leading cause of disability with devastating sequelae. Upper limb spasticity is one of them. Nevertheless, not all the muscles are equally affected, as some may turn spastic or paretic and other remain intact. This unique pathophysiological mosaic dictates a precise therapeutic plan. Existing spasticity treatment has significant drawbacks due to its unspecific targeting and short duration. A causal, life-lasting treatment, precisely adapted to every single patient's needs and to disease pattern, is currently missing. Hyperselective muscle denervation and subsequent cognitive reinnervation with appropriate unaffected donor nerves may break the pathological spastic circuit and provide volitional muscle control. With this pioneering study we will perform cognitive nerve transfers to spastic muscles and will prospectively investigate their effects on clinical, electrophysiological, molecular-biological and histological level. Accurate donor nerve selection will be for the first time quantified through motor unit number estimation with high-density needle electromyography. This revolutionary concept can open the window to a new era of therapeutic possibilities for stroke victims.


Eligibility criteria: Inclusion Criteria:

* Are undergoing nerve transfers
* Age from 18 to 75 years old
* Minimum of 1 year interval after stroke
* Are able to understand German or English
* Medical Research Council (MRC) Muscle scale for donor nerves: M4 or M5
* Walking patients, with or without crutches
* Good general health condition and social support

For the control group:

* Age 18-75 years old
* Indication for ulnar nerve release and submuscular transposition for compression neuropathy in the elbow
* No other neurological disorders

Exclusion Criteria:

* Stroke earlier than 3 years at the time of first consultation
* Lower limb spasticity and patients mobile with wheel chair

Primary outcomes:
measure: Chedoke Arm and Hand Activity Inventory (CAHAI-9) score
timeFrame: 0-24 months
measure: Modified Ashworth Scale
timeFrame: 0-24 months
measure: Changes in electrophysiological muscle activity after nerve transfers
timeFrame: 0-24 months
Secondary outcomes:
measure: Changes in muscle satellite cell population (%) in spastic muscles and comparison with healthy control group
timeFrame: During surgery- 24 months
measure: The Action Research Arm Test (ARAT)
timeFrame: 0-24 months
measure: The Disabilities of the Arm, Shoulder and Hand (DASH) score
timeFrame: 0-24 months
measure: Motor Unit Number Estimation of donor and spastic muscles
timeFrame: 0-24 months
measure: Comparison of collagen content between spastic and healthy muscles
timeFrame: During surgery- 12 months
measure: Changes in sarcomere length (μm) in spastic muscles
timeFrame: During surgery- 12 months
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: General Hospital of Vienna
Study officials:
affiliation: Department of Surgery, Medical University of Vienna
name: Oskar Aszmann, Prof
role: STUDY_DIRECTOR
References:
citation: Urban PP, Wolf T, Uebele M, Marx JJ, Vogt T, Stoeter P, Bauermann T, Weibrich C, Vucurevic GD, Schneider A, Wissel J. Occurence and clinical predictors of spasticity after ischemic stroke. Stroke. 2010 Sep;41(9):2016-20. doi: 10.1161/STROKEAHA.110.581991. Epub 2010 Aug 12.
citation: Wissel J, Manack A, Brainin M. Toward an epidemiology of poststroke spasticity. Neurology. 2013 Jan 15;80(3 Suppl 2):S13-9. doi: 10.1212/WNL.0b013e3182762448.
citation: Sommerfeld DK, Gripenstedt U, Welmer AK. Spasticity after stroke: an overview of prevalence, test instruments, and treatments. Am J Phys Med Rehabil. 2012 Sep;91(9):814-20. doi: 10.1097/PHM.0b013e31825f13a3.
citation: Zheng MX, Hua XY, Feng JT, Li T, Lu YC, Shen YD, Cao XH, Zhao NQ, Lyu JY, Xu JG, Gu YD, Xu WD. Trial of Contralateral Seventh Cervical Nerve Transfer for Spastic Arm Paralysis. N Engl J Med. 2018 Jan 4;378(1):22-34. doi: 10.1056/NEJMoa1615208. Epub 2017 Dec 20.
citation: Qiu YQ, Du MX, Yu BF, Jiang S, Feng JT, Shen YD, Xu WD. Contralateral Lumbar to Sacral Nerve Rerouting for Hemiplegic Patients After Stroke: A Clinical Pilot Study. World Neurosurg. 2019 Jan;121:12-18. doi: 10.1016/j.wneu.2018.09.118. Epub 2018 Sep 26.
citation: Khalifeh JM, Dibble CF, Van Voorhis A, Doering M, Boyer MI, Mahan MA, Wilson TJ, Midha R, Yang LJS, Ray WZ. Nerve transfers in the upper extremity following cervical spinal cord injury. Part 1: Systematic review of the literature. J Neurosurg Spine. 2019 Jul 12;31(5):629-640. doi: 10.3171/2019.4.SPINE19173. Print 2019 Nov 1.
citation: Faturi FM, Lopes Santos G, Ocamoto GN, Russo TL. Structural muscular adaptations in upper limb after stroke: a systematic review. Top Stroke Rehabil. 2019 Jan;26(1):73-79. doi: 10.1080/10749357.2018.1517511. Epub 2018 Sep 17.
citation: Smith LR, Pichika R, Meza RC, Gillies AR, Baliki MN, Chambers HG, Lieber RL. Contribution of extracellular matrix components to the stiffness of skeletal muscle contractures in patients with cerebral palsy. Connect Tissue Res. 2021 May;62(3):287-298. doi: 10.1080/03008207.2019.1694011. Epub 2019 Nov 28.
citation: Mandeville RM, Brown JM, Sheean GL. Semi-quantitative electromyography as a predictor of nerve transfer outcome. Clin Neurophysiol. 2019 May;130(5):701-706. doi: 10.1016/j.clinph.2019.02.008. Epub 2019 Feb 28.
citation: Barreca S, Gowland CK, Stratford P, Huijbregts M, Griffiths J, Torresin W, Dunkley M, Miller P, Masters L. Development of the Chedoke Arm and Hand Activity Inventory: theoretical constructs, item generation, and selection. Top Stroke Rehabil. 2004 Fall;11(4):31-42. doi: 10.1310/JU8P-UVK6-68VW-CF3W.