Clinical trial NCT04101916: PAS in Subacute SCI
Official title: Paired Associative Stimulation in Subacute Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Spinal Cord Injuries
Spinal Cord Diseases
Lead sponsor: Helsinki University Central Hospital
Sponsor class: OTHER
First posted: 2019-09-24
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The aim is 20 participants and the anticipated dropout percentage is 20%, therefore maximum number of randomized patients will be 24. If there will be no dropouts, only 20 patients will be recruited.
Primary purpose: TREATMENT

Brief summary: The investigators have recently shown in incomplete SCI patients that long-term paired associative stimulation is capable of restoring voluntary control over some paralyzed muscles and enhancing motor output in the weak muscles. In this study, the investigators will administer long-term paired associative stimulation to patients with incomplete cervical level SCI at the subacute stage, and investigate its effectiveness for upper extremity rehabilitation.


Eligibility criteria: Inclusion Criteria:

1. SCI caused by an external trauma or SCI caused by nontraumatic non-progressive disease of the spinal cord
2. Cervical level injury, tetraplegia
3. Time from injury/onset of symptoms 1-4 months
4. Medical condition stable
5. Residual neural connectivity in upper extremity: some voluntary activity in finger muscles or MEPs obtainable from distal hand muscles

Exclusion Criteria:

1. Diagnosed brain damage, visible in MRI or CT.
2. No activity in hands/fingers and no MEPs recorded from distal hand muscles.
3. Epilepsy
4. Metal inclusion in the head area
5. High intracranial pressure
6. Pacemaker
7. Implanted hearing device
8. Progressive diseases of spinal cord or brain (e.g. malignant tumors, degenerative diseases).
9. History of malignant tumor within the past 5 years.
10. Previous head or spinal cord injury affecting the motor performance of upper extremities.
11. Congenital anomaly in the anatomical structure of spinal canal/cord or dura.
12. Significant systemic disease or other condition that could cause neurological deficit, or may affect subject's capability to undergo investigation-related procedures.
13. Acute severe infection.
14. Contraindications for MRI.
15. Current severe psychiatric diseases.
16. Current chronic drug and/or alcohol abuse.
17. Pregnancy.
18. Severe emergency care polyneuropathy
19. Pressure ulcer affecting the subject's capability to undergo the procedure safely

Primary outcomes:
measure: Daniels and Worthingham's Muscle Testing
timeFrame: Change from baseline score immediately after, 6 months after and 1 year after last stimulation session
measure: Spinal Cord Independence Measure (SCIM)
timeFrame: Change from baseline score immediately after, 6 months after and 1 year after last stimulation session
Secondary outcomes:
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: BioMag laboratory, Helsinki University Central Hospital
state: Uusimaa
Study officials:
References:
citation: Tolmacheva A, Savolainen S, Kirveskari E, Lioumis P, Kuusela L, Brandstack N, Ylinen A, Makela JP, Shulga A. Long-Term Paired Associative Stimulation Enhances Motor Output of the Tetraplegic Hand. J Neurotrauma. 2017 Sep 15;34(18):2668-2674. doi: 10.1089/neu.2017.4996. Epub 2017 Jul 21.
citation: Shulga A, Lioumis P, Zubareva A, Brandstack N, Kuusela L, Kirveskari E, Savolainen S, Ylinen A, Makela JP. Long-term paired associative stimulation can restore voluntary control over paralyzed muscles in incomplete chronic spinal cord injury patients. Spinal Cord Ser Cases. 2016 Jul 14;2:16016. doi: 10.1038/scsandc.2016.16. eCollection 2016.
citation: Tolmacheva A, Makela JP, Shulga A. Increasing the frequency of peripheral component in paired associative stimulation strengthens its efficacy. Sci Rep. 2019 Mar 7;9(1):3849. doi: 10.1038/s41598-019-40474-0.
citation: Shulga A, Lioumis P, Kirveskari E, Savolainen S, Makela JP, Ylinen A. The use of F-response in defining interstimulus intervals appropriate for LTP-like plasticity induction in lower limb spinal paired associative stimulation. J Neurosci Methods. 2015 Mar 15;242:112-7. doi: 10.1016/j.jneumeth.2015.01.012. Epub 2015 Jan 15.
citation: Shulga A, Zubareva A, Lioumis P, Makela JP. Paired Associative Stimulation with High-Frequency Peripheral Component Leads to Enhancement of Corticospinal Transmission at Wide Range of Interstimulus Intervals. Front Hum Neurosci. 2016 Sep 23;10:470. doi: 10.3389/fnhum.2016.00470. eCollection 2016.
citation: Tolmacheva A, Savolainen S, Kirveskari E, Brandstack N, Makela JP, Shulga A. Paired associative stimulation improves hand function after non-traumatic spinal cord injury: A case series. Clin Neurophysiol Pract. 2019 Aug 13;4:178-183. doi: 10.1016/j.cnp.2019.07.002. eCollection 2019.
citation: Rodionov A, Savolainen S, Kirveskari E, Makela JP, Shulga A. Restoration of hand function with long-term paired associative stimulation after chronic incomplete tetraplegia: a case study. Spinal Cord Ser Cases. 2019 Oct 1;5:81. doi: 10.1038/s41394-019-0225-5. eCollection 2019.