ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03356769
Recruitment Status : Recruiting
First Posted : November 29, 2017
Last Update Posted : November 29, 2017
Sponsor:
Collaborator:
Shijiazhuang Yiling Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Peking Union Medical College Hospital

November 2, 2017
November 29, 2017
November 29, 2017
November 20, 2017
November 20, 2019   (Final data collection date for primary outcome measure)
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)

Same as current
No Changes Posted
  • 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
  • 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
  • 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
  • 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)
  • Changes of cognitive condition [ Time Frame: Baseline, Week 12 ]
    Raven standard reasoning test
  • 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
Same as current
  • genetic analysis [ Time Frame: Baseline, Week 12 ]
    genotype-phenotype correlation; evaluated by severity of symptoms and treatment effects
  • 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)
Same as current
 
Aspirin as an add-on Treatment of Refractory Epilepsy in Tuberous Sclerosis Complex
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.

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.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Patients, investigators, site personnel, and the sponsor's study team were masked to treatment allocation, but allocation was not concealed from personnel in charge of drug supply, and implementation of the randomisation list. The Data Safety Monitoring Board (DSMB) independent statistician and programmer were semi-blind to treatment allocation at the time of DSMB meetings.
Primary Purpose: Treatment
  • Tuberous Sclerosis Complex
  • Aspirin
  • Epilepsy
  • Cognitive Decline
  • Skin Lesions
  • 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 Name: antiepileptic drugs
  • Drug: Placebo
    placebo, 5mg/Kg/d, once every day, 25mg per tablets
    Other Name: Placebo tablets
  • Experimental: experimental:asprin & AEDS
    Aspirin 5mg/kg,maximum 300mg; once a day plus AEDS
    Interventions:
    • Drug: Aspirin
    • Drug: AED
  • Placebo Comparator: control: placebo & AEDS
    placebo 5mg/kg,maximum 300mg; once a day plus AEDS
    Interventions:
    • Drug: AED
    • Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
98
Same as current
November 20, 2020
November 20, 2019   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
6 Years to 30 Years   (Child, Adult)
No
Contact: Qing Liu, MD PhD 133-6630-5331 drliuqing@126.com
Contact: Hui Xu, MD 69156874 pumchkyc@126.com
China
 
 
NCT03356769
JS-1425
Yes
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: Undecided
Peking Union Medical College Hospital
Peking Union Medical College Hospital
Shijiazhuang Yiling Pharmaceutical Co. Ltd
Principal Investigator: Qing Liu, MD PhD Peking Union Medical College Hospital
Peking Union Medical College Hospital
September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP