What is the mechanism of action of this treatment?

The most common treatments for Tuberous Sclerosis, particularly mTOR inhibitors like Sirolimus, work by targeting the mTOR pathway, which is often dysregulated in TSC patients due to mutations in the TSC1 or TSC2 genes. These mutations lead to uncontrolled cell growth and proliferation, resulting in the formation of benign tumors in various organs. Sirolimus inhibits the mTOR pathway, thereby reducing cell growth and proliferation, which helps to shrink these tumors and manage symptoms. This mechanism is crucial for TSC patients as it directly addresses the underlying cause of their condition, offering a targeted approach to treatment that can improve quality of life and reduce complications.

What side effects are associated with this type of intervention?

Common side effects of mTOR inhibitors like Sirolimus, used in the treatment of Tuberous Sclerosis, include mouth ulcers, respiratory infections, hyperlipidemia, and delayed wound healing. Other potential side effects are increased susceptibility to infections, liver function abnormalities, and gastrointestinal issues such as diarrhea. These side effects necessitate careful monitoring and management by healthcare providers.

What prior FDA approvals exist?

The FDA has approved several mTOR inhibitors for the treatment of Tuberous Sclerosis Complex (TSC). Everolimus, an mTOR inhibitor, is approved for the treatment of TSC-associated renal angiomyolipoma and subependymal giant cell astrocytoma (SEGA) that require therapeutic intervention but are not amenable to surgery. Sirolimus, another mTOR inhibitor, is being studied for its potential to prevent or delay seizure onset in TSC infants, highlighting the ongoing research into mTOR pathway modulation as a therapeutic strategy for TSC.

What other types of research exist?

A promising novel alternative to Sirolimus for Tuberous Sclerosis patients is the combination of rapamycin and MK-2206, an Akt inhibitor. This combination has demonstrated potential efficacy in preclinical models.

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Sirolimus for Tuberous Sclerosis (TSC-STEPS Trial)

Phase 2

Recruiting

Led By Darcy A Krueger, MD, PhD

Research Sponsored by Darcy Krueger

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Has a confirmed diagnosis of TSC based on established clinical or genetic criteria

Subject must be 0-6 months of age at the time of enrollment with a corrected age of at least 39 weeks

Must not have

Prior, planned, or anticipated neurosurgery within 3 months of the baseline visit

Has a TSC-associated condition for which mTOR treatment is clinically indicated

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 12 and 24 months of age

Summary

This trial is testing sirolimus, a medication that helps control symptoms of Tuberous Sclerosis Complex (TSC), in infants. The goal is to prevent or delay seizures, which can impact long-term brain development. Sirolimus works by turning down the activity of a center in the body that doesn't function properly in TSC. Sirolimus has been studied for its potential to control seizures in pediatric patients with TSC and has shown promising results in improving seizure control.

Who is the study for?

This trial is for infants diagnosed with Tuberous Sclerosis Complex (TSC), aged between 0-6 months. They must not have started any seizure medications, special diets, or other treatments related to TSC and should be generally healthy without significant prematurity (born after at least 30 weeks of gestation).

What is being tested?

The study tests the safety and effectiveness of Sirolimus in preventing or delaying seizures in infants with TSC. It's a Phase II trial where participants are randomly given either Sirolimus or a placebo without knowing which one they receive.

What are the potential side effects?

While specific side effects for this trial aren't listed, Sirolimus can typically cause immune system suppression leading to increased infection risk, mouth sores, acne-like skin conditions, diarrhea, nausea, and potentially abnormal liver or kidney function.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have been diagnosed with TSC through clinical tests or genetic analysis.

Select...

My baby is between 0-6 months old and corrected age is at least 39 weeks.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have had, or will have, brain surgery within 3 months of starting the trial.

Select...

I have a condition linked to TSC that needs mTOR treatment.

Select...

I do not have any serious illness or active infections currently.

Select...

I have had seizures or they were found on an EEG.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 12 and 24 months of age

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~12 and 24 months of age

This trial's timeline: 3 weeks for screening, Varies for treatment, and 12 and 24 months of age for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Seizures

Safety -- adverse events

Secondary study objectives

EEG Biomarkers

MRI Biomarkers

Neurodevelopmental Outcomes

+2 more

Side effects data

From 2008 Phase 4 trial • 293 Patients • NCT00118742

29%

Diarrhoea

18%

Abdominal Pain

16%

Nausea

16%

Headache

16%

Fatigue

16%

Hepatitis C

14%

Vomiting

14%

Pyrexia

14%

Leukopenia

12%

Oedema Peripheral

11%

Insomnia

10%

Anaemia

10%

Hyperkalaemia

10%

Tremor

10%

Back Pain

10%

Hypertension

Cough

Pruritis

Arthralgia

Neutropenia

Abdominal Pain Upper

Dizziness

Pain in Extremity

Hepatic Enzyme Increased

Dyspnoea

Constipation

Sinusitis

Weight Decreased

Blood Creatinine Increased

Liver Function Test Abnormal

White Blood Cell Count Decreased

Muscle Spasms

Jaundice

Renal Failure

Decreased Appetite

Weight Increased

Upper Respiratory Tract Infection

Nasopharyngitis

Asthenia

Incision Site Pain

Depression

Anorexia

Night Sweats

Oropharyngeal Pain

Rhinorrhoea

Hyperlipidaemia

Thrombocytopenia

Pleural Effusion

Myalgia

Rash

Acne

Incisional Hernia

Sepsis

Pneumonia

Hypokalaemia

Renal Failure Acute

Hepatic Neoplasm Malignant

Hypoglycaemia

Urinary Retention

Clostridium Difficile Colitis

Cerebral Haemorrhage

Hepatic Artery Stenosis

Portal Vein Thrombosis

Gastrointestinal Tract Adenoma

Encephalopathy

Atrial Flutter

Transplant Rejection

Confusional State

Blood Alkaline Phosphatase Increased

Multi-Organ Failure

Chest Pain

Non-Small Cell Lung Cancer Metastatic

Benign Prostatic Hyperplasia

Ventricular Tachycardia

Febrile Neutropenia

Hepatic Failure

Epstein-Barr Virus Associated Lymphoproliferative Disorder

Gastritis

Crohn's Disease

Abdominal Hernia

Inappropriate Antidiuretic Hormone Secretion

Gastrointestinal Haemorrhage

Cardiac Failure Congestive

Blood Glucose Increased

Spinal Osteoarthritis

Hypercholesterolaemia

Convulsion

Peritonitis

Haemorrhage Intracranial

Deep Vein Thrombosis

Inguinal Hernia

Viral Infection

Acarodermatitis

Atrial Fibrillation

Malaise

Hepatic Cancer Metastatic

Adenocarcinoma

B-Cell Lymphoma

Desmoid Tumour

Pulmonary Embolism

Stomatitis

Influenza

Staphylococcal Infection

Umbilical Hernia

Hepatic Function Abnormal

Hyponatraemia

Bacteraemia

Cellulitis

Clostridial Infection

Diverticulitis

Escherichia Urinary Tract Infection

Lactobacillus Infection

Lobar Pneumonia

Pseudomonal Sepsis

Post Procedural Haemorrhage

Procedural Pain

Biliary Anastomosis Complication

Complications of Transplanted Kidney

Bile Duct Obstruction

Bile Duct Stenosis

Biliary Tract Disorder

Autoimmune Hepatitis

Cholestasis

Lung Disorder

Pulmonary Oedema

Sinus Congestion

Embolism Venous

Orthostatic Hypotension

Vasculitis

Hyperglycaemia

Graft Versus Host Disease

100%

80%

60%

40%

20%

Study treatment Arm

CellCept + CNI (Tacrolimus or Cyclosporine)

CellCept + Sirolimus

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: SirolimusExperimental Treatment1 Intervention

Sirolimus

Group II: PlaceboPlacebo Group1 Intervention

Placebo

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Sirolimus

2013

Completed Phase 4

~2750

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Tuberous Sclerosis, particularly mTOR inhibitors like Sirolimus, work by targeting the mTOR pathway, which is often dysregulated in TSC patients due to mutations in the TSC1 or TSC2 genes. These mutations lead to uncontrolled cell growth and proliferation, resulting in the formation of benign tumors in various organs. Sirolimus inhibits the mTOR pathway, thereby reducing cell growth and proliferation, which helps to shrink these tumors and manage symptoms. This mechanism is crucial for TSC patients as it directly addresses the underlying cause of their condition, offering a targeted approach to treatment that can improve quality of life and reduce complications.