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Tuberous Sclerosis ComplexPhase 2NCT03356769

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

A Phase 2 study testing Aspirin and AED in people with Tuberous Sclerosis Complex and Aspirin, run by Peking Union Medical College Hospital at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 6 to 30 years
Conditions the study is for
Tuberous Sclerosis Complex, Aspirin, Epilepsy
What is being tested?
Aspirin and AED
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
98 participants
Where
1 siteChina
Study dates
20 Nov 2017to 20 Nov 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 6-30 years old TSC patients (by Gomez criteria)
  • more than 8 seizures occurred in the 4-week baseline time,with no continued seizure-free time of more than 10 days a month
  • 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
  • patients who had been treated with rapamycin should have been stopped for more than 3 months
  • vagus nerve stimulation (VNS) is allowed as a previous or current therapy and would maintain until the end of the trial

Who cannot join

  • Subependymal Giant Cell Astrocytoma and requires immediate surgery；
  • a history of intracranial surgery within 6 months;
  • epilepsy caused by improper use of drugs;
  • patients treated with aspirin had severe or intolerant side effects, including gastrointestinal ulcer, bleeding, aspirin allergy, and other conditions;
  • psychogenic seizures;
  • severe renal dysfunction and infection
Show all 9Show fewer
  • pregnant women and lactating women
  • not regular follow-up
  • 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.

Trial locations and contacts

1 site in 1 country.

Qing Liu, MD PhD contact

133-6630-5331

drliuqing@126.com

Hui Xu, MD contact

69156874

pumchkyc@126.com

China1 site, 1 recruiting

  • Department of Neurology, Peking Union Medical College Hospital

    Beijing, Beijing Municipality, 100005

    Qing Liu, MD, PhD, 86-10-13366305331, drliuqing@126.com

    Recruiting

Other trials in China

About this study

Official title: 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.

Read the 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.

Being tested
Aspirin, AED, Placebo
Keywords
refractory seizure, cognitive impairment, electroencephalography improvement, seizure reduction, seizure free, aspirin
Medical subject headings
Tuberous Sclerosis, Epilepsy, Cognitive Dysfunction, Seizures

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AspirinDrug

    Also called acetylsalicylic acid, enteric-coated aspirin tablets

    low-dose of aspirin, 5mg/Kg/d, once every day, 25mg per tablets

  • AEDDrug

    Also called antiepileptic drugs

    maintain the dosages and the drugs throughout the 3-month observation time

  • PlaceboDrug

    Also called Placebo tablets

    placebo, 5mg/Kg/d, once every day, 25mg per tablets

Study groups in NCT03356769
Study groupRoleWhat they receive
experimental：asprin & AEDSExperimentalAspirin 5mg/kg，maximum 300mg; once a day plus AEDS
Receives: Drug: Aspirin; Drug: AED
control: placebo & AEDSPlacebo comparatorplacebo 5mg/kg，maximum 300mg; once a day plus AEDS
Receives: Drug: AED; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of reduction in seizure frequency

    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)

    Measured: 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 outcomes (6)

  1. Total days of seizure free

    Days of seizure free in a four week observation time

    Measured: Baseline, Week 0-4, Week 4-8, Week 8-12

  2. A mild reduction in seizure frequency

    At least 25% of median seizure frequency reduction comparing with those in the baseline

    Measured: baseline, Week 12

  3. Changes of epileptic discharges in electroencephalogram

    Epileptic discharge on 2-hour video electroencephalogram in frequency detected at the same lead(s) comparing with baseline

    Measured: Baseline, Week 12

  4. Improvement of facial angiofibromas

    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)

    Measured: Baseline, Week 4, Week 8, Week 12

  5. Changes of cognitive condition

    Raven standard reasoning test

    Measured: Baseline, Week 12

  6. Subjective evaluation of treatment-response condition

    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

    Measured: Baseline, Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Nov 2017
  2. Study start20 Nov 2017
  3. Primary completion20 Nov 2021 (estimated)
  4. Study completion20 Nov 2021 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
98 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03356769
Sponsor's protocol ID
JS-1425
Status last verified
Sep 2019
First submitted
2 Nov 2017
Last updated
9 Jun 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Franz DN, Leonard J, Tudor C, Chuck G, Care M, Sethuraman G, Dinopoulos A, Thomas G, Crone KR. Rapamycin causes regression of astrocytomas in tuberous sclerosis complex. Ann Neurol. 2006 Mar;59(3):490-8. doi: 10.1002/ana.20784.

    PubMed 16453317

  • Krueger DA, Care MM, Holland K, Agricola K, Tudor C, Mangeshkar P, Wilson KA, Byars A, Sahmoud T, Franz DN. Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med. 2010 Nov 4;363(19):1801-11. doi: 10.1056/NEJMoa1001671.

    PubMed 21047224

  • Din FV, Valanciute A, Houde VP, Zibrova D, Green KA, Sakamoto K, Alessi DR, Dunlop MG. Aspirin inhibits mTOR signaling, activates AMP-activated protein kinase, and induces autophagy in colorectal cancer cells. Gastroenterology. 2012 Jun;142(7):1504-15.e3. doi: 10.1053/j.gastro.2012.02.050. Epub 2012 Mar 6.

    PubMed 22406476

  • Chen CT, Du Y, Yamaguchi H, Hsu JM, Kuo HP, Hortobagyi GN, Hung MC. Targeting the IKKbeta/mTOR/VEGF signaling pathway as a potential therapeutic strategy for obesity-related breast cancer. Mol Cancer Ther. 2012 Oct;11(10):2212-21. doi: 10.1158/1535-7163.MCT-12-0180. Epub 2012 Jul 23.

    PubMed 22826466

  • Northrup H, Krueger DA; International Tuberous Sclerosis Complex Consensus Group. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 Iinternational Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013 Oct;49(4):243-54. doi: 10.1016/j.pediatrneurol.2013.08.001.

    PubMed 24053982

  • Overwater IE, Rietman AB, Bindels-de Heus K, Looman CW, Rizopoulos D, Sibindi TM, Cherian PJ, Jansen FE, Moll HA, Elgersma Y, de Wit MC. Sirolimus for epilepsy in children with tuberous sclerosis complex: A randomized controlled trial. Neurology. 2016 Sep 6;87(10):1011-8. doi: 10.1212/WNL.0000000000003077. Epub 2016 Aug 10.

    PubMed 27511181

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Aspirin and AED in people with Tuberous Sclerosis Complex and Aspirin, run by Peking Union Medical College Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 9 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Qing Liu, MD PhD (133-6630-5331, drliuqing@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the 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）). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03356769, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2020.

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