Aspirin as an add-on Treatment of Refractory Epilepsy in Tuberous Sclerosis Complex

June 5, 2020 updated by: Peking Union Medical College Hospital

A Placebo-controlled Study of Efficacy & Safety of Aspirin as an add-on Treatment in Patients With Tuberous Sclerosis Complex (TSC) & Refractory Seizures

There had been much evidence in aspirin controlling tumorous conditions conducted by basic researches, especially through mammilian target of rapamycin (mTOR) pathway. The investigator observed efficacy of aspirin in the treatment of tuberous sclerosis complex (TSC) in one child who got Kawasaki disease and in the addition four TSC patients with epilepsy. The investigator intend to evaluate whether aspirin would be an effective add-on treatment in TSC patients with refractory seizures.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

There is no optional treatment for patients with tuberous sclerosis complex (TSC) and refractory epilepsy.The investigator observed efficacy of aspirin in the treatment of in one child who got Kawasaki disease. Subsequent adjunctive aspirin therapy in four patients yielded a reducted frequency of seizure for 51.2-89.7%. The investigator intend to evaluate whether aspirin would be an effective add-on treatment in TSC patients with refractory seizures.

Refractory epilepsy was defined as more than 8 times of epileptic events in 4 weeks at baseline, and had been given more than two antiepileptic drugs maintaining for more than 3 months.TSC patients aged 6-30 years' old would be recruited with refractory seizures and randomly assigned to two groups, aspirin and antiepileptic drugs(AEDS) group and placebo-AEDS group after written informed consent be obtained. Patients and their guardians would be instructed to record their own seizure diary on the epileptic events and report monthly.The primary outcome would be reduction of seizure frequency (measured by average seizure frequency and response rate). The secondary outcome would include seizure-free days, seizure-free rates, changes in EEG, changes of facial angiofibromas, and exposure-response relationship analysis.The study is designed as a placebo-controlled, randomized, blinded evaluation trial.

Study Type

Interventional

Enrollment (Anticipated)

98

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100005
        • Recruiting
        • Department of Neurology, Peking Union Medical College Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 years to 30 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. 6-30 years old TSC patients (by Gomez criteria)
  2. more than 8 seizures occurred in the 4-week baseline time,with no continued seizure-free time of more than 10 days a month
  3. more than two antiepileptic drugs (AED) had been administered but fail to control the situation; maintaining with 1 or more than 1 AEDS for over 2 months and intending to continue with the drugs
  4. patients who had been treated with rapamycin should have been stopped for more than 3 months
  5. vagus nerve stimulation (VNS) is allowed as a previous or current therapy and would maintain until the end of the trial

Exclusion Criteria:

  1. Subependymal Giant Cell Astrocytoma and requires immediate surgery；
  2. a history of intracranial surgery within 6 months;
  3. epilepsy caused by improper use of drugs;
  4. patients treated with aspirin had severe or intolerant side effects, including gastrointestinal ulcer, bleeding, aspirin allergy, and other conditions;
  5. psychogenic seizures;
  6. severe renal dysfunction and infection
  7. pregnant women and lactating women
  8. not regular follow-up
  9. other: because when children and adolescents suffering from influenza or chickenpox, using aspirin may cause a rare life-threatening Reye syndrome (characterized with persistent vomiting）, should temporary withdrawal, medication needs to consult a physician before using again.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: experimental：asprin & AEDS
Aspirin 5mg/kg，maximum 300mg; once a day plus AEDS
Drug: Aspirin
low-dose of aspirin, 5mg/Kg/d, once every day, 25mg per tablets
Other Names:
  • acetylsalicylic acid
  • enteric-coated aspirin tablets
Drug: AED
maintain the dosages and the drugs throughout the 3-month observation time
Other Names:
  • antiepileptic drugs
PLACEBO_COMPARATOR: control: placebo & AEDS
placebo 5mg/kg，maximum 300mg; once a day plus AEDS
Drug: AED
maintain the dosages and the drugs throughout the 3-month observation time
Other Names:
  • antiepileptic drugs
Drug: Placebo
placebo, 5mg/Kg/d, once every day, 25mg per tablets
Other Names:
  • Placebo tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of reduction in seizure frequency
Time Frame: Baseline phase (week 0); Observation phase week 1（±1 days）；Observation phase week 2（±2 days）；Observation phase week 4（±3 days）d；Observation phase week 8（±7 days）；Observation phase week 12（±14 days）

Estimated by median percentage of seizure frequency reduction and response rate comparing each group with the baseline; response rate is defined as more than 50% of reduction in seizure frequency.

The seizure diary of individual participants would be recorded every day during the trial time by the participants and their guardians. The correct way of recording will be guided by investigator specialized in epileptic disease with discrimination of real or false seizure events.

•seizure information was known within the same period of time (baseline or maintenance phase)
Baseline phase (week 0); Observation phase week 1（±1 days）；Observation phase week 2（±2 days）；Observation phase week 4（±3 days）d；Observation phase week 8（±7 days）；Observation phase week 12（±14 days）

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total days of seizure free
Time Frame: Baseline, Week 0-4, Week 4-8, Week 8-12
Days of seizure free in a four week observation time
Baseline, Week 0-4, Week 4-8, Week 8-12
A mild reduction in seizure frequency
Time Frame: baseline, Week 12
At least 25% of median seizure frequency reduction comparing with those in the baseline
baseline, Week 12
Changes of epileptic discharges in electroencephalogram
Time Frame: Baseline, Week 12
Epileptic discharge on 2-hour video electroencephalogram in frequency detected at the same lead(s) comparing with baseline
Baseline, Week 12
Improvement of facial angiofibromas
Time Frame: Baseline, Week 4, Week 8, Week 12
We observed improvement of facial lesions concurrent with seizure control, in the size, color and number of facial angiofibromas. The improvement will be estimated by Physician's Global Assessement Overall Score (PGA, 7-grade:more than -25%, -25% to 25%, 25-50%, 50-75%, 75%-100%, 100% improvement)
Baseline, Week 4, Week 8, Week 12
Changes of cognitive condition
Time Frame: Baseline, Week 12
Raven standard reasoning test
Baseline, Week 12
Subjective evaluation of treatment-response condition
Time Frame: Baseline, Week 12
evaluated by physician/Caregiver who is familial with the patient with Physician's Global Assessement Overall Score (PGA, 7-grade:more than -25%, -25% to 25%, 25-50%, 50-75%, 75%-100%, 100% improvement ) and a two-page age-specific questionaire
Baseline, Week 12

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
genetic analysis
Time Frame: Baseline, Week 12
genotype-phenotype correlation; evaluated by severity of symptoms and treatment effects
Baseline, Week 12
treatment-response annotation
Time Frame: Baseline phase (week 0); Observation phase week 1（±1 days）；Observation phase week 2（±2 days）；Observation phase week 4（±3 days）d；Observation phase week 8（±7 days）；Observation phase week 12（±14 days）
Charts of seizure frequency reduction on different treatment time points would show the fluctuations of treatment effects (eg. the effective time)
Baseline phase (week 0); Observation phase week 1（±1 days）；Observation phase week 2（±2 days）；Observation phase week 4（±3 days）d；Observation phase week 8（±7 days）；Observation phase week 12（±14 days）

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking Union Medical College Hospital

Collaborators

Shijiazhuang Yiling Pharmaceutical Co. Ltd

Investigators

  • Principal Investigator: Qing Liu, MD PhD, Peking Union Medical College Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

November 20, 2017

Primary Completion (ANTICIPATED)

November 20, 2021

Study Completion (ANTICIPATED)

November 20, 2021

Study Registration Dates

First Submitted

November 2, 2017

First Submitted That Met QC Criteria

November 23, 2017

First Posted (ACTUAL)

November 29, 2017

Study Record Updates

Last Update Posted (ACTUAL)

June 9, 2020

Last Update Submitted That Met QC Criteria

June 5, 2020

Last Verified

September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • JS-1425

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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