Nerve Transfers in Post-stroke Spasticity

Spasticity as Sequela of Stroke Clinical Trial

Official title:

Outcome Measurements After Cognitive Nerve Transfers to Spastic Muscles in Stroke Patients

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04437056
• Other study ID #: EK 2319/2019
• Status: Enrolling by invitation
• Phase: N/A
• Start date: September 1, 2020
• Est. completion date: December 31, 2025

Study information

• Verified date: April 2022
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 20
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Muscle Spasticity
• Nerve Transfers
• Spasticity as Sequela of Stroke
• Stroke

Intervention

Procedure:
• Cognitive nerve transfers to spastic upper extremity muscles in stroke patients
Based on the fact that upper motor neuron syndrome after stroke is presented with variable clinical features, usually without affecting in the same way the entire upper extremity, we aim to investigate the efficacy of nerve transfers to spastic muscles after stroke using as donor nerves that innervate unaffected ipsilateral volitionally controlled muscles.

Locations

Country	Name	City	State
Austria	General Hospital of Vienna	Vienna

Sponsors (3)

Lead Sponsor	Collaborator
Medical University of Vienna	Imperial College London, Shirley Ryan AbilityLab

Country where clinical trial is conducted

Austria, 

References & Publications (10)

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. — View 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. — View 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 12:1-12. doi: 10.3171/2019.4.SPINE19173. [Epub ahead of print] Review. — View 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. — View 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. — View 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. — View 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. Review. — View 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. — View 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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Chedoke Arm and Hand Activity Inventory (CAHAI-9) score	Patients can reach a score for CAHAI 9 between 9 to 63. The lower the score, the greater impairment.	0-24 months
Primary	Modified Ashworth Scale	A score of 1 indicates no resistance, and 5 indicates rigidity. A 1+ scoring category indicates resistance through less than half of the movement. Scores range from 0-4, with 6 choices .	0-24 months
Primary	Changes in electrophysiological muscle activity after nerve transfers	Low frequency-dependent depression of H-wave (in mV)	0-24 months
Secondary	Changes in muscle satellite cell population (%) in spastic muscles and comparison with healthy control group	Muscle biopsies from spastic muscles will be obtained during the surgery of nerve transfers. The muscle satellite cell population (%) will be calculated with the use of Flow Cytometry and be compared to the one of healthy muscles of control group. There will be no recruitment procedure for the control group. Routinely, when we carry out surgery for ulnar nerve release in the elbow and nerve transposition, a part of the flexor carpi ulnaris muscle needs to be excised and discarded. After obtaining informed consent from patients for further use of their biological material, we will collect these muscles and use them as control group.	During surgery- 24 months
Secondary	The Action Research Arm Test (ARAT)	The total score on the ARAT ranges from 0 to 57, with the lowest score indicating that no movements can be performed, and the upper score indicating normal performance.	0-24 months
Secondary	The Disabilities of the Arm, Shoulder and Hand (DASH) score	Scores range from 0 (no disability) to 100 (most severe disability).	0-24 months
Secondary	Motor Unit Number Estimation of donor and spastic muscles	High density electromyography with fine needle electrodes will be applied to allow an accurate estimation of motor units (absolute number) in donor muscles, in spastic muscles and in newly-innervated muscles	0-24 months
Secondary	Comparison of collagen content between spastic and healthy muscles	Muscle biopsies from spastic muscles will be obtained during the surgery of nerve transfers. Collagen content of spastic muscles (%) will be calculated with the use of Picrosirius red staining and bright field light microscopy and be compared with healthy muscles of control group. There will be no recruitment procedure for the control group. Routinely, when we carry out surgery for ulnar nerve release in the elbow and nerve transposition, a part of the flexor carpi ulnaris muscle needs to be excised and discarded. After obtaining informed consent from patients for further use of their biological material, we will collect these muscles and use them as control group.	During surgery- 12 months
Secondary	Changes in sarcomere length (µm) in spastic muscles	Biopsy of a muscle fascicle from spastic muscles will be obtained during the surgery of nerve transfers with the use of dedicated clamps and will be fixed in formalin. The sarcomere length will be calculated with the use of fractional laser. The sarcomere length of spastic muscles will be compared with the sarcomere length of healthy control group muscles.	During surgery- 12 months