The Effectiveness and Safety of Resective Epilepsy Surgery for TRE

Clinical Evaluation of the Effectiveness and Safety of Resective Epilepsy Surgery for Tuberous Sclerosis Complex Related Epilepsy

A prospective cohort studies to identify clinical seizure control, cognitive changes, and safety in resective epilepsy surgery in patients with TSC-related drug-resistant epilepsy.

Study Overview

• Status: Active, not recruiting
• Conditions: Epilepsy; Tuberous Sclerosis Complex
• Intervention / Treatment: Procedure: Surgery

Detailed Description

Two hundred candidates are recruited and assigned to the control and surgery groups with 100 cases in each group, respectively. All patients will accept first-stage pre-enrollment evaluations and patients in surgery group will accept second-stage invasive evaluation.

All patients will be advised to visit the hospitals for examination each year after enrollment. Seizure outcomes will be assessed with reference to patients' seizure diaries and caregivers' oral statements by both neurosurgeons and neurologists.

All adverse effects will be classified according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (2017).

Statistical analyses were conducted using SPSS (version 26.0, IBM, USA), Stata (version 16.0, Stata Corp LLC, USA), and R (version 4.3.3, R Foundation for Statistical Computing, Austria). Outcomes were presented according to data type as percentages, mean ± standard deviation, or median (interquartile range, IQR).

Multiple imputation was employed to address missing data for IQ and QOL at enrollment and the 2-year follow-up. A sensitivity analysis was conducted to assess the robustness of the multiple imputation results. The "mi impute regress" statement in Stata facilitated the multiple imputations. 20 T-tests were utilized for comparing continuous variables, with results reported as mean ± standard deviation. The Mann-Whitney U test was applied for non-normally distributed continuous variables, presenting results as median values and IQRs. Chi-square and Fisher's exact tests were used for univariate analyses. A significance level of p < 0.05 was established.

To account for differences in covariates between the surgery and medicine groups, propensity score matching (PSM) was performed. Based on PSM, Kaplan-Meier curves and the log-rank test were utilized to analyze time-to-seizure recurrence differences between the surgery and medicine groups. Additionally, multivariable Cox proportional hazards regression was applied to predict risk factors for postoperative seizure recurrence within a 51-month follow-up period after PSM.

• Study Type: Observational
• Enrollment (Actual): 200

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100045
      • Beijing Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients from participating medical institutions

Description

Inclusion Criteria:

• 2 years old and above, no gender restriction, TSC gene monitoring with or without abnormality
• Diagnosis of tuberous sclerosis- related drug-resistant epilepsy
• Epilepsy course for more than 1 year
• Patients who have taken 3 or more reasonable choices with appropriate and tolerable antiepileptic drugs (excluding mTOR inhibitors and traditional Chinese medicine and prescriptions) had seizures more than 12 times in the 3 months before enrollment
• The family members agreed to enroll and signed the informed consent.

Exclusion Criteria：

• Obvious renal angiomyolipoma, pulmonary lymphoma leiomyomatosis, and subventricular giant cell astrocytoma
• Abnormal heart, lung, liver, and kidney functions and coagulation function
• Preoperative evaluation, it is considered that no surgical treatment is needed
• The patient received other craniocerebral surgical treatment within 1 year during the follow-up period

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Control Group; Patients in the surgery group will accept exclusive rational medicine therapy.
Surgery Group; Patients in the surgery group will undergo resective surgery combined with rational medicine therapy.	Procedure: Surgery; Resective surgery included lobectomy (partial or total brain lobe resection), tuberectomy (epileptogenic tuber resection), and tuberectomy plus (resection of epileptogenic tuber and perituberal gyri). Tuberectomy was typically performed on the epileptogenic tuber within or near an eloquent area. Lobectomy was performed in patients with large epileptogenic tubers in the brain lobes. Multiple lobectomies, tuberectomies, tuberectomies plus, and lobectomy combined with tuberectomy/tuberectomies plus were further performed in patients with multiple epileptogenic tubers.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
% of patients with ILAE grading	The grading made by ILAE for the classification of outcome with respect to epileptic seizures following epilepsy surgery. It contains a total of 6 levels. The higher the level, the worse the result. We will count the percentage of patients at each level.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life: QOLIE-31	QOLIE-31 is suitable for patients 14 years and older. QOLCE-76 is applied to patients aged 2-13 by parents.	3 years
IQ	Wechsler Preschool and Primary Scale of Intelligence（WPPSI-III），Wechsler Intelligence Scale for Children (WISC-IV) and Wechsler Adult Intelligence Scale (WAIS-IV)，3 scales will be used for different ages to measure IQ. Higher scores mean better outcomes.	3 years

Collaborators and Investigators

• Sponsor: Beijing Children's Hospital
• Collaborators: Xiangya Hospital of Central South University; Peking University People's Hospital; The Second Hospital of Hebei Medical University; West China Hospital; Beijing Sanbo Brain Hospital; First Affiliated Hospital Xi'an Jiaotong University; Xuanwu Hospital, Beijing; Shandong Provincial Hospital; Shanghai Children's Hospital; The First Hospital of Jilin University; Henan Provincial People's Hospital; Capital Medical University; The First Affiliated Hospital of Shanxi Medical University; The First Affiliated Hospital of University of Science and Technology of China; Shenzhen Children's Hospital; Guangdong 999 Brain Hospital; The Affiliated Nanjing Brain Hospital of Nanjing University Medical School; Xinqiao Hospital, Amry Medical University; First Medical Center, PLA General Hospital; Fourth Medical Center, PLA General Hospital; Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2019
• Primary Completion (Estimated): March 15, 2027
• Study Completion (Estimated): March 15, 2027

Study Registration Dates

• First Submitted: December 9, 2019
• First Submitted That Met QC Criteria: December 12, 2019
• First Posted (Actual): December 13, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 16, 2025
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: epilepsy; tuberous sclerosis complex; resective epilepsy surgery
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neoplasms; Genetic Diseases, Inborn; Neurodegenerative Diseases; Congenital Abnormalities; Heredodegenerative Disorders, Nervous System; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Hamartoma; Neoplasms, Multiple Primary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Sclerosis; Tuberous Sclerosis; Epilepsy
• Other Study ID Numbers: TRE-RES

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No