Developing Treatment, Treatment Validation and Treatment Scope in the Setting of an Autism Clinical Trial

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01260961
Recruitment Status : Active, not recruiting
First Posted : December 15, 2010
Last Update Posted : November 29, 2016
Information provided by (Responsible Party):
Rutgers, The State University of New Jersey

Brief Summary:

Dr. Sherie Novotny of the Department of Psychiatry at UMDNJ-RWJMS and collaborators are starting a treatment trial to determine whether Docosa Hexanoic Acid(DHA), the major omega-3 fatty acid found in the brain and a component of fish oil, has any effects on the symptoms of autism.

We propose to carry out a trial to test the effect of DHA compared to a placebo (a pill with no drug in it) on several aspects of autism in children and adolescents, in a 12-week clinical study with children or adolescents in the age group of 5-17 with a diagnosis of Autism Spectrum Disorder. Additionally this trial will study genes related to the therapeutic agent, DHA, and biomarkers related to DHA in the urine.

Condition or disease Intervention/treatment Phase
Autism Dietary Supplement: Placebo Dietary Supplement: Docosahexanoic Acid Not Applicable

Detailed Description:

Growing evidence supports oxidative stress may contribute to autism. Docosa Hexanoic Acid(DHA)is a normal substance that is present in large amounts in the brain and can be used by the body to produce natural antioxidants. Our hope is that supplementing DHA in individuals with autism may improve some aspects of their functioning. Specifically our aims are:

Aim 1. To assess the effect of DHA vs. placebo treatment on the global severity of child and adolescent autistic disorder, via a 12-week double blind placebo-controlled parallel study. Global severity will be assessed by the Autism Diagnostic Observation Schedule-Generic (ADOS-G) and additionally in younger children by the Vineland Adaptive Behavior Scale.

Aim 2. To assess the effect of DHA vs. placebo treatment on behavioral symptoms and functional ability in children with autism. Assessment will be by the Aberrant Behavior Checklist (ABC)-Community Version11.

Aim 3. To develop an improved protocol and study design based upon these studies for future large scale studies of DHA in the autistic population.

Aim 4. Monitor the effects of therapy on the isoprostane biomarker. Aim 5: Develop additional biomarkers that correlate with autism and with therapy. We will extend the analyses to neuroprostanes and resolvins. We will measure: (i) Urinary excretion of the isoprostane metabolites, 2,3 Dinor-5,6 dihydro-PGF2t and iPF4α-VI. (ii) DHA derived resolvins D2, D4, D5 and D6 and neuroprotectin.

Aim 6: Confirm our preliminary results by correlating increased isoprostane excretion with GSTM1*0 copy number in individuals with autism.

Aim 7: In the same way, correlate GSTM1*0 copy number with response to therapy assessed by diminution of isoprostane excretion during therapy.

Aim 8: Study additional biomarkers developed through Hypothesis #2 for correlation with GSTM1*0 copy number and response to therapy to identify additional gene-biomarker correlations.

Aim 9: Study additional polymorphisms of genes related to DHA metabolism, for association with autism, gene-biomarker correlations, and correlation with response to therapy.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 132 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Developing Treatment, Treatment Validation and Treatment Scope in the Setting of an Autism Clinical Trial
Study Start Date : November 2010
Actual Primary Completion Date : November 2013
Estimated Study Completion Date : December 2017

Arm Intervention/treatment
Active Comparator: Docosa Hexanoic Acid Dietary Supplement: Docosahexanoic Acid
The volunteers will start on the 200 mg daily of the DHA capsule and will not increase their dose during the study.
Other Name: DHA

Placebo Comparator: Placebo Dietary Supplement: Placebo
The volunteers will start on the 200 mg daily of the placebo and will not increase their dose during the study.

Primary Outcome Measures :
  1. Amelioration of phenotypic features of autism [ Time Frame: three years ]
    Amelioration of phenotypic features of autism as measured by a significant decrease from the baseline, in global severity of autism score and Aberrant Behavior Checklist scores

Secondary Outcome Measures :
  1. oxidative stress biomarkers [ Time Frame: Three years ]

    We will be measuring isoprostane 8-iso-PGF2a.

    The measurements will be in ng mg Creatinine and we expect a significant decrease in levels from the baseline.

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Ages Eligible for Study:   5 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Meets DSM-IV, ADI, and ADOS criteria for autistic disorder
  • Age 5-17.
  • Outpatients
  • Parent or legal guardian signing informed consent, and assent documented for patient with demonstrated capacity to provide it.
  • Sexually active females of childbearing potential must use an acceptable method of birth control (oral contraceptive medications [the administration of which must be supervised by a parent or guardian], IUD, depot medication, double barrier or tubal ligation) and have a negative serum pregnancy test prior to entry into the study.
  • Subjects with history of seizures, who have been seizure-free for more than or equal to 6 months on a stable dose of anticonvulsant medication.Non-medicated subjects with a history of seizures who have been seizure-free for more than or equal to 6 months.Subjects with abnormal EEG but no clinical seizures.

Exclusion Criteria:

  • Subjects who are pregnant or nursing mothers.
  • Sexually active females of childbearing potential who are not using adequate birth control measures (detailed above in inclusion criteria).
  • Subjects with overall adaptive behavior scores below the age of two years on the Vineland Adaptive Behavior Rating Scale.
  • Subjects with active or unstable epilepsy.
  • Subjects with any of the following past or present mental disorders: schizophrenia, schizoaffective disorder, major depressive disorder, bipolar I or II disorders or substance abuse disorders.
  • Subjects who are a serious suicidal risk.
  • Subjects with clinically significant or unstable medical illness that would contraindicate participation in the study, including hematopoietic or cardiovascular disease, pancreatitis, liver toxicity, and polycystic ovary syndrome
  • Subjects reporting history of encephalitis, phenylketonuria, tuberous sclerosis, fragile X syndrome, anoxia during birth, pica, neurofibromatosis, hypomelanosis of Ito, hypothyroidism, Duchenne muscular dystrophy, and maternal rubella.
  • Patients with history of the following:gastrointestinal, liver, or kidney, or other known conditions which will presently interfere presently with the absorption, distribution, metabolism, or excretion of drugs, cerebrovascular disease or brain trauma, clinically significant unstable endocrine disorder, such as hypo- or hyperthyroidism, recent history or presence of any form of malignancy
  • Treatment within the previous 30 days with any drug known to a well-defined potential for toxicity to a major organ
  • Subjects with clinically significant abnormalities in laboratory tests or physical exam
  • Subjects likely to require ECT.
  • Subjects unable to tolerate taper from psychoactive medication if necessary.
  • Subjects with a history of hypersensitivity or severe side effects associated with the use of divalproex sodium, or other an ineffective prior therapeutic trial of omega three fatty acids.
  • Subjects who have received any of the following interventions within the prescribed period before starting treatment-investigational drugs within the previous 30 days.
  • Subjects who have begun any new alternative non-medication treatments, such as diet, vitamins, and psychosocial therapy, within the previous three months.
  • Subjects with any organic or systemic disease or patients who require a therapeutic intervention, not otherwise specified, which would confound the evaluation of the safety of the study medication.
  • Subjects who reside in a remote geographical area who do not have regular access to transportation to the clinical facility.
  • If a patient is not doing well enough (defined by CGI-AD Severity score of 3-"mildly ill" or better)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01260961

United States, New Jersey
Piscataway, New Jersey, United States, 08854
Sponsors and Collaborators
Rutgers, The State University of New Jersey
Principal Investigator: Sherie Novotny, MD Rutgers-RWJMS

Responsible Party: Rutgers, The State University of New Jersey Identifier: NCT01260961     History of Changes
Other Study ID Numbers: 0220080189
First Posted: December 15, 2010    Key Record Dates
Last Update Posted: November 29, 2016
Last Verified: November 2016

Additional relevant MeSH terms:
Autistic Disorder
Child Development Disorders, Pervasive
Neurodevelopmental Disorders
Mental Disorders