SCED Myokines and Cognition in SCI

Spinal Cord Injuries Clinical Trial

Official title:

Myokines and Cognitive Aging in People With Spinal Cord Injury: a Single Case Experimental Design Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05822297
• Other study ID #: CoBes22.055
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 2024
• Est. completion date: September 2024

Study information

• Verified date: December 2023
• Source: Adelante, Centre of Expertise in Rehabilitation and Audiology
• Contact: Wouter Vints, MD
• Phone: +31455282828
• Email: wouter.vints[@]adelantegroep.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Rationale: Individuals with spinal cord injury (SCI) suffer from accelerated cognitive aging. In able-bodied individuals, a vast amount of studies have shown that exercise interventions can improve cognitive function. Myokines (i.e. factors released into the blood stream from muscle cells) are considered one of the mediators of this beneficial effect. Neuromuscular electrical stimulation (NMES), used to replace or support muscle training in disabled individuals with poor exercise possibilities, was shown to elicit a large release of myokines (in some studies larger than following voluntary exercise). However, so far, the effects of NMES on cognitive function have never been studied before. In fact, only one study has previously investigated the effect of exercise on cognitive function in persons with SCI.

Objective: The primary aim is to assess to what extent a 12 week intervention with NMES to the quadriceps muscles of people with SCI can change their performance on a set of cognitive tests. Secondarily, the investigators will measure to what extent NMES to the quadriceps muscles of people with SCI induces changes in blood levels of the myokine brain-derived neurotrophic factor (BDNF), which is considered a potential mediator of the exercise-cognition effect, facilitating neuroplastic processes.

Study design: A single case experimental design (SCED) with sequential multiple baseline time series and a single-armed prospective study design, with a random duration of the baseline phase ranging from 3 to 6 weeks, an intervention phase of 12 weeks, and a 12 week period without measurements, followed by a follow-up phase of 3 weeks; in addition to a single-armed prospective study design.

Study population: Individuals (n = 15) aged 18 years and older with a chronic SCI (>1y post-injury) and with visible or palpable contraction of the quadriceps muscles upon NMES will be recruited at the rehabilitation centre of Adelante in Hoensbroek, the Netherlands.

Intervention: The study participants will receive 30min of NMES using surface electrodes on the quadriceps muscles three times per week for a total duration of 12 weeks.

Main study parameters/endpoints: The primary outcome is cognitive function changes which will be measured using a secured smartphone application (e.g. m-Path). Secondary outcome measures are changes in the blood myokine levels of BDNF and changes in cognitive outcome scores on an verbal cognitive test battery.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 15
• Est. completion date: September 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Persons with spinal cord injury

• Completeness of injury: American Spinal Injury Association (ASIA) Impairment Scale (AIS) A, B or C

• Level of injury: L2 or higher

• At least 18 years old

• Chronic stage (> 1 year) since injury

• No previous surgery to the quadriceps muscles

• Intact hand function

• Able to use apps on smartphone (i.e. participants should have their own smartphone and should not have disabilities that impair them to operate it independently)

• Able to follow the instructions of placing the surface electrodes of the NMES device correctly or to have someone else put the electrodes for them

• Dutch as a native language

Exclusion Criteria:

• Malignant processes, or history of undergoing chemotherapy, or history of radiotherapy to the head

• No visible or palpable contraction of the quadriceps muscle upon electrical stimulation

• Intolerance to electrical stimulation of the quadriceps muscle

• Recent or current participation in an electrical stimulation-induced exercise or therapy program in which regular electrical stimulation was given (up to 6 months prior to study inclusion)

• Known neurodegenerative disorder, such as Alzheimer's disease or Parkinson's disease

• Known psychiatric disorder, such as major depressive disorder or bipolar disorder

• Current pressure ulcer

• History of severe autonomic dysreflexia

• Metal implants in the electrical stimulation area

• Intrathecal baclofen (ITB) device

• Pregnancy

Related Conditions & MeSH terms

• Cognitive Decline
• Cognitive Dysfunction
• Spinal Cord Injuries

Intervention

Device:
• Neuromuscular electrical stimulation
NMES will consist of a 12 week electrical stimulation program, three times a week. Electrical stimulation will be done on the quadriceps muscles of both legs simultaneously. For each leg, one electrode is placed on the proximal side and one on the distal side of the quadriceps muscle. Electrical stimulation sessions will take 30min, at a stimulation frequency of 50Hz, an intensity where we can at least see a visible or palpable contraction with a maximum intensity of 100mA (we will choose the highest intensity that is easily supported by the participant without inducing discomfort) and a pulse width of 400µs. The activation within the activation-rest cycle consists of a 1s ramp-up, 7s full activation and 1s ramp-down, followed by 18s rest. Every 4 weeks the rest period will be diminished with 3s until a total of 9s.

Locations

Country	Name	City	State
Netherlands	Adelante Zorggroep	Maastricht	Limburg

Sponsors (1)

Lead Sponsor	Collaborator
Adelante, Centre of Expertise in Rehabilitation and Audiology

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in executive function	response time (in ms) on the momentary digital symbol substitution task	measured a total of 54-63 times in 30-33 weeks time
Secondary	Neurocognitive test battery, change in cognitive scores	A neurocognitive test battery will be used to assess cognitive changes on various cognitive domains over time	before and after the 12 week intervention and after a 12 week follow-up
Secondary	Concentration of brain-derived neurotrophic factor (BDNF)	Brain-derived neurotrophic factor will be measured in blood of the participants	before and after the 12 week intervention and after a 12 week follow-up
Secondary	Self-perceived cognitive function	measured using the cognitive failures index (CFI), ranging from 0-100, with a higher score indicating more subjective cognitive problems	before and after the 12 week intervention and after a 12 week follow-up
Secondary	Pain score	measured using the McGill Pain Questionnaire (MPQ), ranging from 0-78, with a higher score indicating higher subjective pain level	before and after the 12 week intervention and after a 12 week follow-up
Secondary	Fatigue	measured using the Fatigue Severity Scale (FSS), ranging from 1-7, with a higher score indicating more fatigue/higher impact of fatigue on daily activities	before and after the 12 week intervention and after a 12 week follow-up
Secondary	Participation in daily life activities	measured using the Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-P), ranging from 0-100, with a higher score indicating larger participation in daily life activities	before and after the 12 week intervention and after a 12 week follow-up
Secondary	Spasticity	measured using the Perceived Resistance to Passive Movement (PRPM) test at all four limbs.	before and after the 12 week intervention
Secondary	Electrically-evoked quadriceps strength	measured using the MicroFET2 dynamometer	before and after the 12 week intervention