Cognitive Function and Glymphatic System in Children With Epilepsy

Epilepsy Clinical Trial

Official title:

The Effect of Respiratory Muscle Performance on Cognitive Functions in Children With Epilepsy: Monitoring With Glymphatic System Activation and Neuropeptides

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06143241
• Other study ID #: 16.11.2023
• Status: Recruiting
• Phase: N/A
• Start date: March 1, 2024
• Est. completion date: August 24, 2024

Study information

• Verified date: May 2024
• Source: Ege University
• Contact: Miray Baser, MSc
• Phone: +905456936293
• Email: miraybaser1[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Epilepsy, one of the most common neurological disorders in childhood, is a chronic brain disease characterized by neurobiological, psychological and cognitive effects. Neuropeptide-Y (NPY) and neural growth factor (NGF) play a role in different pathological processes seen in epileptogenesis. Neuron-specific enolase (NSE), a quantitative indicator of brain damage, has been shown to exhibit elevated serum levels in individuals with epilepsy and is associated with cognitive functions.

It is reported that the glymphatic system, which is associated with epileptic seizures, is a treatment method that can prevent cognitive impairment by preventing the accumulation of toxic waste proteins.

Inspiratory muscle training, one of the respiratory physiotherapy techniques, is used as supportive treatment in patients with weak respiratory muscle strength. Weakness in respiratory muscle strength has also been detected in the epilepsy group in which the glymphatic system is affected.

40 children with epilepsy who meet the inclusion criteria and volunteer to participate in the study will participate. Children with epilepsy will be divided into two groups: experimental group (n = 20) and control group (n = 20) using the block randomization method.

The experimental group will be given Inspiratory Muscle Training (IMT) with the Threshold device for 30 minutes every day for 8 weeks after routine medication use. The control group will be followed only with routine medication use.

Demographic information of all participants will be recorded. Respiratory function will be evaluated with a portable spirometer device, respiratory muscle strength will be evaluated with a portable electronic mouth pressure measurement device, and cognitive performance will be evaluated with the Serial Digit Learning Test (SDLT).

Biochemical analyses; Serum levels of neuron specific enolase (NSE), neuropeptide-Y (NPY) and neural growth factor (NGF) will be determined with an ELISA kit set. The glymphatic system will be evaluated with Diffusion Tensor Imaging Analysis Across the Perivascular Space (DTI-ALPS). In both groups, the initial evaluations will be repeated after 8 weeks.

This research project was planned to prevent the development of seizures and improve biochemical parameters, glymphatic system dysfunction and cognitive functions with inspiratory muscle training in pediatric epilepsy patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: August 24, 2024
• Est. primary completion date: June 24, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years to 17 Years

Eligibility

Inclusion Criteria:

• Diagnosed with absence and rolandic type epilepsy according to the International League Against Epilepsy (ILAE) classification.

• No previous respiratory physiotherapy.

• Maximal Inspiratory Pressure (MIP) value is below the expected value according to age and gender.

• Co-operative.

Exclusion Criteria:

• Diagnosed with respiratory system disease.

• Has kyphoscoliosis and/or advanced postural alignment problems that affect respiratory function.

• Have severe mental problems.

• Receiving ketogenic diet application.

• Have any neuromuscular disease.

• Have severe cardiac involvement, pulmonary embolism, mesenteric or portal thrombosis.

• Diagnosis of inflammatory disease or C-reactive protein (CRP) analysis above normal limits.

• The presence of orthopedic surgery.

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Epilepsy
• Seizure, Epileptic
• Seizures

Intervention

Device:
• Threshold IMT
Threshold is used in respiratory muscle training in the form of resistance loading.

Drug:
• Antiepileptic medication
They will continue their antiepileptic medication prescribed by their doctor.

Locations

Country	Name	City	State
Turkey	Ege University	Izmir	Bornova

Sponsors (1)

Lead Sponsor	Collaborator
Ege University

Country where clinical trial is conducted

Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Respiratory Muscle Strength	Respiratory muscle strength will be measured according to American Thoracic Society (ATS) / European Respiratory Society (ERS) criteria using a portable electronic mouth pressure measurement device (micro RPM). A measurement result of 80 cmH2O and above indicates a good result.	It will be measured at baseline and at the end of the experiment (at the end of 8 weeks).
Primary	Spirometer	It will be performed using a portable spirometer (Cosmed Pony FX, Italy). The test will be performed in a seated position with the patient being asked to first take a deep breath and then exhale rapidly into the spirometer device. A nose clip will be used during exhalation. The forced vital capacity (FVC) value will be recorded in litres and %.	It will be measured at baseline and at the end of the experiment (at the end of 8 weeks).
Primary	Spirometer	It will be performed using a portable spirometer (Cosmed Pony FX, Italy). The test will be performed in a seated position with the patient being asked to first take a deep breath and then exhale rapidly into the spirometer device. A nose clip will be used during the exhalation. The forced expiratory volume in one second (FEV1) value will be recorded in litres and %.	It will be measured at baseline and at the end of the experiment (at the end of 8 weeks).
Primary	Spirometer	It will be performed using a portable spirometer (Cosmed Pony FX, Italy). The test will be performed in a seated position with the patient being asked to first take a deep breath and then exhale rapidly into the spirometer device. A nose clip will be used during the exhalation. The forced expiratory volume in one second/forced vital capacity (FEV1/FVC) value will be recorded in litres and %.	It will be measured at baseline and at the end of the experiment (at the end of 8 weeks).
Primary	Spirometer	It will be performed using a portable spirometer (Cosmed Pony FX, Italy). The test will be performed in a seated position with the patient being asked to first take a deep breath and then exhale rapidly into the spirometer device. A nose clip will be used during exhalation. The peak expiratory flow (PEF) value will be recorded in litres and %.	It will be measured at baseline and at the end of the experiment (at the end of 8 weeks).
Primary	Neuron specific enolase (NSE)	Blood samples will be collected interictal and serum will be separated and stored. Analyses will be performed by ELISA.	It will be measured at baseline and at the end of the experiment (at the end of 8 weeks).
Primary	Neuropeptide-Y (NPY)	Blood samples will be collected interictal and serum will be separated and stored. Analyses will be performed by ELISA.	It will be measured at baseline and at the end of the experiment (at the end of 8 weeks).
Primary	Neural growth factor (NGF)	Blood samples will be collected interictal and serum will be separated and stored. Analyses will be performed by ELISA.	It will be measured at baseline and at the end of the experiment (at the end of 8 weeks).
Primary	Serial Digit Learning Test (SDLT)	Evaluates short-term memory and learning ability. In the test content, there are two separate sequences of 8 or 9 digits in which the digits from 1 to 9 are mixed according to the age and education level of the participant. The selected sequence is read to the subject in order and the subject is asked to remember and say the sequence in the correct order.	It will be measured at baseline and at the end of the experiment (at the end of 8 weeks).
Primary	Diffusion Tensor Imaging Analysis Across Perivascular Space (DTI-ALPS)	It is used to measure glymphatic system activation. A rectangular ROI is drawn and fiber orientations and diffusivities in all three directions along the x-, y-, and z-axes are obtained as voxel levels. Among several voxels, for each fiber on the same x-axis (projection, association, and subcortical fibers), one voxel is selected that shows the most common orientation in each fiber. The DTI-ALPS index is the average of two sets of diffusivity values perpendicular to the dominant fibers in the tissue, namely the x-axis diffusivity in the area of projection fibers (Dxproj) and the x-axis diffusivity in the area of association fibers (Dxassoc), the y-axis diffusivity in the area of projection fibers (Dyproj) and the area of association fibers. It is calculated as the ratio of the z-axis diffusivity (Dzaccoc) to its average.	It will be measured at baseline and at the end of the experiment (at the end of 8 weeks).