Cognitive Function and Glymphatic System in Children With Epilepsy

Sponsor

Ege University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06143241

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Epilepsy, one of the most common neurological disorders in childhood, is a chronic brain disease characterised by neurobiological, psychological and cognitive effects. Brain-derived neurotrophic factor (BDNF), 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 this has been associated with cognitive function.

In neurological diseases, glymphatic fluid transport facilitated by astrocytic end feet and their expression of aquaporin-4 water channels is impaired. Activation of astrocytes is associated with tumour necrosis factor-α (TNF-α). The glymphatic system is reported as a therapeutic modality that may prevent cognitive impairment by preventing toxic waste protein accumulation.

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

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

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

Demographic information of all participants will be recorded. Respiratory function will be assessed with a portable spirometer device, respiratory muscle strength with a portable electronic mouth pressure measuring device, and cognitive performance with the Number Sequence Learning Test (NSLT). EEG results, which will be used as epilepsy diagnosis method, will be recorded from the hospital database. Biochemical analyses; serum levels of brain derived neurotrophic factor (BDNF), neuron specific enolase (NSE), tumour necrosis factor alpha (TNF-α), neuropeptide-Y (NPY) and neural growth factor (NGF) will be performed with ELISA kit set. The initial evaluations performed at baseline in both groups will be repeated after 8 weeks.

This research project was planned to prevent seizure development and improve biochemical parameters and cognitive function in paediatric epilepsy patients with inspiratory muscle training.

Condition or Disease	Intervention/Treatment	Phase
Epilepsy Cognitive Dysfunction Seizure, Epileptic	Device: Threshold IMT Drug: Antiepileptic medication	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Children diagnosed with epilepsy will be divided into two groups as experimental group and control group using block randomisation method.Children diagnosed with epilepsy will be divided into two groups as experimental group and control group using block randomisation method.

Masking:

Double (Participant, Outcomes Assessor)

Masking Description:

Patients will not be informed about the intergroup practice. The person who will carry out the evaluations will not be informed about the application.

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jan 24, 2024

Anticipated Primary Completion Date :

Feb 24, 2024

Anticipated Study Completion Date :

Aug 24, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental Group It consists of 20 children diagnosed with epilepsy who will receive inspiratory muscle training following routine medication use. The experimental group will receive inspiratory muscle training with the Thershold device for 30 minutes every day for 8 weeks.	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.
Active Comparator: Control Group The control group consists of 20 children diagnosed with epilepsy who will only be followed up with routine medication.	Drug: Antiepileptic medication They will continue their antiepileptic medication prescribed by their doctor.

Arm

Intervention/Treatment

Experimental: Experimental Group

It consists of 20 children diagnosed with epilepsy who will receive inspiratory muscle training following routine medication use. The experimental group will receive inspiratory muscle training with the Thershold device for 30 minutes every day for 8 weeks.

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.

Active Comparator: Control Group

The control group consists of 20 children diagnosed with epilepsy who will only be followed up with routine medication.

Drug: Antiepileptic medication

They will continue their antiepileptic medication prescribed by their doctor.

Outcome Measures

Primary Outcome Measures

Respiratory Muscle Strength [It will be measured at baseline and at the end of the experiment (at the end of 8 weeks).]
It will be measured using a portable electronic mouth pressure measuring device (micro RPM brand).
Spirometer [It will be measured at baseline and at the end of the experiment (at the end of 8 weeks).]
Pulmonary function test will be performed using Cosmed Pony FX.
Brain-derived neurotrophic factor (BDNF) [It will be measured at baseline and at the end of the experiment (at the end of 8 weeks).]
Blood samples will be collected interictal and serum will be separated and stored. Analyses will be performed by ELISA.
Neuron specific enolase (NSE) [It will be measured at baseline and at the end of the experiment (at the end of 8 weeks).]
Blood samples will be collected interictal and serum will be separated and stored. Analyses will be performed by ELISA.
Tumour necrosis factor alpha (TNF-α) [It will be measured at baseline and at the end of the experiment (at the end of 8 weeks).]
Blood samples will be collected interictal and serum will be separated and stored. Analyses will be performed by ELISA.
Neuropeptide-Y (NPY) [It will be measured at baseline and at the end of the experiment (at the end of 8 weeks).]
Blood samples will be collected interictal and serum will be separated and stored. Analyses will be performed by ELISA.
Neural growth factor (NGF) [It will be measured at baseline and at the end of the experiment (at the end of 8 weeks).]
Blood samples will be collected interictal and serum will be separated and stored. Analyses will be performed by ELISA.
Number Sequence Learning Test (NDSLT) [It will be measured at baseline and at the end of the experiment (at the end of 8 weeks).]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

8 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosed with absence and rolandic type epilepsy according to International League Against Epilepsy (ILAE) classification.
No previous respiratory physiotherapy.
Maximal Inspiratory Pressure (MIP) value was below the expected value according to age and gender.
Co-operative.

Exclusion Criteria:

Diagnosed with respiratory system disease.
Have kyphoscoliosis and/or advanced postural alignment problems that affect respiratory function.
Have severe mental problems.
Those who follow the ketogenic diet.
Any neuromuscular disease.
Children with severe cardiac involvement, pulmonary embolism, mesenteric or portal thrombosis.
Children with a diagnosis of inflammatory disease or C-reactive protein (CRP) analysis above normal limits.
History of orthopaedic surgery.