PAS in Subacute SCI

• Sponsor: Helsinki University Central Hospital (Other)
• Overall Status: Enrolling by invitation
• CT.gov ID: NCT04101916
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 38
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Spinal Cord Injuries; Spinal Cord Diseases	Device: Paired associative stimulation; Device: Sham paired associative stimulation	N/A

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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.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.
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Paired Associative Stimulation in Subacute Spinal Cord Injury
• Actual Study Start Date: Oct 10, 2019
• Anticipated Primary Completion Date: Oct 10, 2022
• Anticipated Study Completion Date: Dec 10, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Paired Associative Stimulation	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 Comparator: Sham	Device: Sham paired associative stimulation; Sham transcranial magnetic stimulation and sham peripheral nerve stimulation.

Outcome Measures

Primary Outcome Measures

1. Daniels and Worthingham's Muscle Testing [Change from baseline score immediately after, 6 months after and 1 year after last stimulation session]

   hand muscle strength is evaluated on 0-5 scale (0=no movement, 5=normal)

2. Spinal Cord Independence Measure (SCIM) [Change from baseline score immediately after, 6 months after and 1 year after last stimulation session]

   standard SCIM evaluation

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	BioMag laboratory, Helsinki University Central Hospital	Helsinki	Uusimaa	Finland	00029

Sponsors and Collaborators

• Helsinki University Central Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

• Rodionov A, Savolainen S, Kirveskari E, Mäkelä 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.
• Shulga A, Lioumis P, Kirveskari E, Savolainen S, Mäkelä 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.
• Shulga A, Lioumis P, Zubareva A, Brandstack N, Kuusela L, Kirveskari E, Savolainen S, Ylinen A, Mäkelä 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.
• Shulga A, Zubareva A, Lioumis P, Mäkelä 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. eCollection 2016.
• Tolmacheva A, Mäkelä 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.
• Tolmacheva A, Savolainen S, Kirveskari E, Brandstack N, Mäkelä 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.
• Tolmacheva A, Savolainen S, Kirveskari E, Lioumis P, Kuusela L, Brandstack N, Ylinen A, Mäkelä 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.

• Responsible Party: Anastasia Shulga, Principle Investigator, Helsinki University Central Hospital
• ClinicalTrials.gov Identifier: NCT04101916
• Other Study ID Numbers: WFL-FI-15/19
• First Posted: Sep 24, 2019
• Last Update Posted: Mar 16, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Spinal Cord Injuries; Spinal Cord Diseases

Study Results

No Results Posted as of Mar 16, 2022