Efficacy and Safety of Lenalidomide for Treatment of Autistic Spectrum Disorders

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

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.

Study Overview

• Status: Completed
• Conditions: Autism
• Intervention / Treatment: Drug: lenalidomide

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 14 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lenalidomide	Drug: lenalidomide; 2.5 mgs per day orally for 12 weeks; 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

Collaborators and Investigators

• Sponsor: Sutter Medical Foundation
• Investigators: Principal Investigator: Michael Chez, MD, Sutter Medical Foundation

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: October 15, 2009
• First Submitted That Met QC Criteria: October 15, 2009
• First Posted (Estimate): October 16, 2009

Study Record Updates

• Last Update Posted (Estimate): May 29, 2013
• Last Update Submitted That Met QC Criteria: April 24, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: lenalidomide; autistic spectrum disorder
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autistic Disorder; Autism Spectrum Disorder; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide
• Other Study ID Numbers: RV-ASD-CHEZ-0329