Efficacy and Safety of Lenalidomide for Treatment of Autistic Spectrum Disorders

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine if lenalidomide (Revlimid®)reduces proinflammatory cytokines including TNF-alpha and may actually alter the clinical course of autism for some children.

Detailed Description
-----------------
Autism currently affects 1:142 births and has no definite cause. Recent research has shown possible identifying markers in neuroglial inflammation with elevated cytokines IL-1, Il-6, and MCP-1 and elevated ratios of CSF/serum levels of TNF-alpha in patients with regressive autism. Lenalidomide (Revlimid®) is an analogue of thalidomide. Based on the improved clinical efficacy predicted for Revlimid® in its effects on TNF-alpha and other immunomodulatory cytokines, this oral compound may prove efficacious with less toxicity compared with thalidomide. The study will evaluate the efficacy of lenalidomide by measurement of changes in EEG, clinical global impression, Childhood Autism Rating Scale, and serum and CSF (if available) TNF-alpha at the end of the study compared with the same measurements at baseline.

Official Title
-----------------
A Phase II Pilot Study to Determine Efficacy and Safety of Lenalidomide (Revlimid) for Treatment of Autistic Spectrum Disorders(ASD) With Regression and Markers of Cerebrospinal Fluid Cytokine Elevation and Elevated TNF-alpha Levels

Conditions
-----------------
Autism

Intervention / Treatment
-----------------
* Drug: lenalidomide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of autistic spectrum disorder as defined by DSM-IV criteria. Inflammatory CSF and serum markers with elevated level of TNF-Alfa (> 50pg/ml) or other Cytokine markers such as IL-1, IL-6 or MECP-1, or serum levels of such cytokines greater than 2X normal levels even in absence of CSF markers. or Patients with interictal epiliptiform EEG changes in the absences of clinical seizures, if CSF inflammatory markers are identified. Patients will maintain any other baseline medications for autistic problems or EEG treatment as long as on these for prior 6-8 weeks with no dosage changes. Mentally impaired minors require a parent or legal guardian to sign the informed consent. Exclusion Criteria: -Diagnosis of PPD-NOS and other autism spectrum disorders. Any serious medical condition, laboratory abnormality, genetic, brain, structural, or psychiatric illness that would prevent the subject from participating. History of neutropenia, thrombocytopenia or other types of myelosuppression or risk factors for myelosuppression. History or risk factors for thromboembolic events. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. Use of any other experimental drug or therapy within 28 days of baseline. Current use of steroids (e.g. dexamethasone, prednisone), anthracyclines (Doxil, Adriamycin). Known hypersensitivity to thalidomide. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs. Any prior use of lenalidomide. Known positive for HIV or infectious hepatitis, type A, B or C or tuberculosis.

Ages Eligible for Study
-----------------
Minimum Age: 6 Years
Maximum Age: 16 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lenalidomide<br> | Drug: lenalidomide<br>* 2.5 mgs per day orally for 12 weeks<br>* Other names: Revlimid;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in TNF-alpha Levels | Change in CSF-TNF-α from baseline to 12 weeks. | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Childhood Autism Rating Scale (CARS)Value From Baseline to 6 Weeks | Change in CARS value from baseline to 6 weeks. Total CARS scores range from a fifteen to 60, with a minimum score of thirty serving as the cutoff for a diagnosis of autism on the mild end of the autism spectrum. | Baseline and 6 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
autistic spectrum disorder, lenalidomide