PAS in Subacute SCI

Spinal Cord Injuries Clinical Trial

Official title:

Paired Associative Stimulation in Subacute Spinal Cord Injury

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04101916
• Other study ID #: WFL-FI-15/19
• Status: Enrolling by invitation
• Phase: N/A
• Start date: October 10, 2019
• Est. completion date: December 10, 2024

Study information

• Verified date: March 2024
• Source: Helsinki University Central Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 24
• Est. completion date: December 10, 2024
• Est. primary completion date: May 10, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Spinal Cord Diseases
• Spinal Cord Injuries

Intervention

Device:
• Paired associative stimulation
Paired associative stimulation (PAS) administered several times per week for 12 weeks to upper limbs. PAS comprises transcranial magnetic stimulation (eXimia magnetic stimulator, Nexstim Ltd, Helsinki, Finland) and peripheral nerve stimulation (given with Dantec Keypoint® electroneuromyography device (Natus Medical Incorporated, Pleasanton, CA, USA)).
• Sham paired associative stimulation
Sham transcranial magnetic stimulation and sham peripheral nerve stimulation.

Locations

Country	Name	City	State
Finland	BioMag laboratory, Helsinki University Central Hospital	Helsinki	Uusimaa

Sponsors (1)

Lead Sponsor	Collaborator
Helsinki University Central Hospital

Country where clinical trial is conducted

Finland, 

References & Publications (7)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Daniels and Worthingham's Muscle Testing	hand muscle strength is evaluated on 0-5 scale (0=no movement, 5=normal)	Change from baseline score immediately after, 6 months after and 1 year after last stimulation session
Primary	Spinal Cord Independence Measure (SCIM)	standard SCIM evaluation	Change from baseline score immediately after, 6 months after and 1 year after last stimulation session