Clinical trial NCT03698136: Electrical Stimulation in Denervated Muscles of the Upper Limbs
Official title: Electrical Stimulation in Denervated Muscles of the Upper Limbs - Effect on Muscle Morphological Properties - a Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tetraplegia
Keywords: tetraplegia
denervated muscles
electrical stimulation
Lead sponsor: Swiss Paraplegic Research, Nottwil
Sponsor class: NETWORK
First posted: 2018-10-05
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Repeated measurement interventional Single Subject Design
Primary purpose: TREATMENT

Brief summary: In the last decade the stimulation of denervated muscles got more attention. Not at least because of the promising results of the RISE project (Use of electrical stimulation to restore standing in paraplegics with long-term denervated degenerated muscles). In this European project it was shown that electrical stimulation of denervated muscles in spinal cord injuries (SCI) increased muscle mass and improved the trophic situation of the lower extremities. Furthermore, structural altered muscle into fat- and connective tissue could be restored into contractile muscle tissue by stimulation. However, only a few studies investigated the effect of direct muscle stimulation in case of peripheral nerve damage in the upper extremities. None investigated the stimulation effect in denervated or partially denervated muscles in the upper extremities in tetraplegic patients.

Detailed description: In the last decade the stimulation of denervated muscles became part of the rehabilitation of spinal cord injuries (SCI). Not at least because of the promising results of the RISE project (Use of electrical stimulation to restore standing in paraplegics with long-term denervated degenerated muscles). In this European project it was shown that electrical stimulation of denervated muscles in SCI increased muscle mass and improved the trophic situation of the lower extremities. Furthermore, structural altered muscle into fat- and connective tissue could be restored into contractile muscle tissue by stimulation. However it has been shown that an extended time after SCI hinders the stimulation impact. The denervation process can be divided in four chronologically running steps. Muscle fibrillations are present some days after lesion followed by a loss of tension during electrical evoked tetanic contraction. After months a severe disorganization of the contractile structure in the muscle occurs and finally ends after years in a replacement of muscle fibers into fat tissue and collagen. The best results have been seen within three years after SCI. A stimulation protocol should be set up to start with single twitches combined with tetanic stimulation patterns according to the patients' improvements. The progression in stimulation training to elicit a tetanic contraction - 40 ms pulse duration with a pulse pause of 10 ms and bursts of 2 sec - could last some month in chronic stage after SCI. The stimulation of denervated muscles of the upper extremities gets more attention. It has been investigated that the cross sectional area of denervated muscle fibers could have been increased by early electrical stimulation. Furthermore, the changes in myosin heavy chain isoform, following denervation could be reversed. That indicates that early onset of stimulation could preserve the contractile muscle structure for possible reinnervation or further treatment options. Specially for tetraplegic patients who could benefit from nerve transfers, could win time for their decision.

Eligibility criteria: Inclusion Criteria:

* traumatic or non-traumatic spinal cord injury
* acute and subacute (≥ 6 weeks) and chronic (≥ 2 years) spinal cord injury
* Age ≥ 18 years
* Level of lesion C3 - Th1
* American Spinal Injury Association Impairment Score (AIS) A/B/C/D
* denervated M. extensor carpi ulnaris or M. abductor pollicis brevis or M. interosseus
* Signed informed consent

Exclusion Criteria:

* innervated or partially innervated M. extensor carpi ulnaris or M. abductor pollicis brevis or M. interosseus
* Patients' inability to follow the study, e.g. mental-health problems, language problems, dementia etc.
* Pregnancy (anamnestic)

Primary outcomes:
measure: Pennation angle (degrees)
timeFrame: Baseline and after 12 weeks of electrical stimulation
Secondary outcomes:
measure: Muscle thickness (mm)
timeFrame: Baseline
measure: Questionaire on participant perception
timeFrame: after 12 weeks of electrical stimulation
Other outcomes:
Locations:
city: Nottwil
country: Switzerland
facility: Swiss Paraplegic Centre Nottwil
state: Luzern
Study officials:
affiliation: Swiss Paraplegic Research, Nottwil
name: Jan Fridén, Prof.Dr.med.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bersch I, Koch-Borner S, Friden J. Electrical stimulation-a mapping system for hand dysfunction in tetraplegia. Spinal Cord. 2018 May;56(5):516-522. doi: 10.1038/s41393-017-0042-2. Epub 2018 Jan 22.
citation: Modlin M, Forstner C, Hofer C, Mayr W, Richter W, Carraro U, Protasi F, Kern H. Electrical stimulation of denervated muscles: first results of a clinical study. Artif Organs. 2005 Mar;29(3):203-6. doi: 10.1111/j.1525-1594.2005.29035.x.
citation: Helgason T, Gargiulo P, Johannesdottir F, Ingvarsson P, Knutsdottir S, Gudmundsdottir V, Yngvason S. Monitoring muscle growth and tissue changes induced by electrical stimulation of denervated degenerated muscles with CT and stereolithographic 3D modeling. Artif Organs. 2005 Jun;29(6):440-3. doi: 10.1111/j.1525-1594.2005.29073.x.
citation: Gordon T, English AW. Strategies to promote peripheral nerve regeneration: electrical stimulation and/or exercise. Eur J Neurosci. 2016 Feb;43(3):336-50. doi: 10.1111/ejn.13005. Epub 2015 Aug 14.
citation: Kern H, Boncompagni S, Rossini K, Mayr W, Fano G, Zanin ME, Podhorska-Okolow M, Protasi F, Carraro U. Long-term denervation in humans causes degeneration of both contractile and excitation-contraction coupling apparatus, which is reversible by functional electrical stimulation (FES): a role for myofiber regeneration? J Neuropathol Exp Neurol. 2004 Sep;63(9):919-31. doi: 10.1093/jnen/63.9.919.