SCED Myokines and Cognition in SCI

NCT05822297 | Unknown

• 1 other identifier: CoBes22.055
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Spinal Cord Injuries; Cognitive Decline

Keywords

Aging; Myokine; Cognition; Spinal cord injury; Neuromuscular electrical stimulation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Neurocognitive test battery, change in cognitive scores

  before and after the 12 week intervention and after a 12 week follow-up

• Concentration of brain-derived neurotrophic factor (BDNF)

  before and after the 12 week intervention and after a 12 week follow-up

• Self-perceived cognitive function

  before and after the 12 week intervention and after a 12 week follow-up

• Pain score

  before and after the 12 week intervention and after a 12 week follow-up

• Fatigue

  before and after the 12 week intervention and after a 12 week follow-up

Study Arms (1)

All participants

EXPERIMENTAL

Each participant will undergo the same procedures and intervention, consisting of a baseline phase, intervention phase and follow-up phase. The length of the baseline phase will be randomized 3, 4, 5 or 6 weeks.

Device: Neuromuscular electrical stimulation

Interventions

Neuromuscular electrical stimulation DEVICE

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.

All participants

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Adelante, Centre of Expertise in Rehabilitation and Audiology: lead

Study Sites (1)

Adelante Zorggroep

Maastricht, Limburg, 6430 AB, Netherlands

Location

Related Publications (1)

• Vints WAJ, Levin O, van Griensven M, Vlaeyen JWS, Masiulis N, Verbunt J, van Laake-Geelen CCM. Neuromuscular electrical stimulation to combat cognitive aging in people with spinal cord injury: protocol for a single case experimental design study. BMC Neurol. 2024 Jun 11;24(1):197. doi: 10.1186/s12883-024-03699-9.

  PMID: 38862912 DERIVED

MeSH Terms

Conditions

Spinal Cord Injuries; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Charlotte van Laake, MD, PhD

  Center of Exertise in Rehabilitation and Audiology, Adelante Zorggroep

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wouter Vints, MD

CONTACT

+31455282828; wouter.vints@adelantegroep.nl

Charlotte van Laake, MD,PhD

CONTACT

+31455282424; charlotte.vanlaake@adelantegroep.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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 Record Dates

• First Submitted: April 7, 2023
• First Posted: April 20, 2023
• Study Start: January 1, 2024
• Primary Completion: September 1, 2024
• Study Completion: September 1, 2024
• Last Updated: December 4, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)