Clinical trial NCT00996931: Efficacy and Safety of Lenalidomide for Treatment of Autistic Spectrum Disorders
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Autism
Keywords: autistic spectrum disorder
lenalidomide
Lead sponsor: Sutter Medical Foundation
Sponsor class: OTHER
First posted: 2009-10-16
Enrollment: 6
Sex: MALE
Minimum age (years): 6
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in TNF-alpha Levels
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Change in Childhood Autism Rating Scale (CARS)Value From Baseline to 6 Weeks
timeFrame: Baseline and 6 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Sutter Medical Foundation
name: Michael Chez, MD
role: PRINCIPAL_INVESTIGATOR
References: