Galantamine Versus Placebo in Childhood Autism

• ClinicalTrials.gov Identifier: NCT00252603
• Recruitment Status: Completed
• First Posted: November 11, 2005
• Last Update Posted: January 29, 2007
• Sponsor: University of Medicine and Dentistry of New Jersey
• Collaborator: National Alliance for Autism Research
• Information provided by: Rutgers, The State University of New Jersey

Study Description

Brief Summary:

Autism is a severe neurodevelopmental disorder that affects up to 16 in 10,000 individuals. It is a pervasive developmental disorder affecting social, communicative, and compulsive/repetitive behaviors characterized by stereotypic complex hand and body movements, craving for sameness, and narrow repetitive interests. Autism severely impacts both the affected individual and family members.

The proposed study is designed to assess the efficacy of treatment with Galantamine vs. placebo in childhood/adolescent autism fulfilling DSM-IV and Autism Diagnostic Interview (ADI) criteria. We therefore hypothesize:

1. Galantamine will be superior to placebo in the acute treatment of global autism.
2. Galantamine will be superior to placebo in improving functional ability.
3. Galantamine will be superior to placebo in improving language function.
4. Galantamine will be superior to placebo improving irritable and hyperactive behavior.
5. Galantamine will be superior to placebo in improving social deficits.

Condition or disease	Intervention/treatment	Phase
Autism; Childhood Autism	Drug: Galantamine	Phase 3

Detailed Description:

Once enrolled in the study, subjects will receive evaluations and testing to determine if they meet the necessary criteria for admission into study treatment. Subjects will not be responsible for the costs of any evaluations or tests conducted as part of this study.

First, subjects will receive a psychiatric and medical evaluation by the study psychiatrist to see if she/he has any psychiatric or medical illnesses that would interfere with their ability to participate in this study. These evaluations may take up to an hour to complete. In addition, subjects will be asked to participate in a psychiatric interview designed to determine the child's diagnosis and current problem areas. The subject's parent will also be asked to fill out psychiatric questionnaires. The interview and questionnaires may take up to 4 hours to complete.

Second, urine and blood samples will be needed for routine tests two times during this study (before any study related tests are done, and at the end of the study). Two teaspoons of blood will be drawn each time. The urine sample will be analyzed in order to assess kidney function and to screen for the presence of drugs (such as cocaine, marijuana, heroin, etc.). A positive drug screen would result in the inability of the child to participate in this study. Drug screen results will be kept confidential. In addition, an electrocardiogram will be performed to determine heartbeat.

Lastly, a pregnancy test will be conducted on the urine sample if the child is female and has reached puberty. The child should not be in this study if she is pregnant or a nursing mother. A positive urine pregnancy test would cause the child to be removed from the study. If the child is sexually active, she must be using an effective method of birth control during her participation in this study. Acceptable methods of birth control are oral contraceptive medications (the administration of which must be parentally supervised), IUD, depot medication and tubal ligation.

Subjects will be assigned by chance to receive either the active medication (Galantamine) or placebo (sugar pill) for 12 weeks, much like the flip of a coin. Neither the parent/child nor the investigator will know which of the two treatments the child is receiving. The child has a 50% chance of being assigned to receive placebo during the study or the active medication, Galantamine, during the study.

The child will need to be seen weekly by the study psychiatrist for the first 4 weeks of the twelve-week study, and every other week for the remaining weeks of the study. During these visits the study psychiatrist will ask the parent for feedback on his/her child's condition and any changes that may be related to the medication, including possible side effects, such as nausea and headaches, and will check the child's condition. The psychiatrist will also record his/her weight. These study visits will generally last approximately 30 minutes.

Study Design

• Study Type: Interventional (Clinical Trial)
• Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: Galantamine Versus Placebo in Childhood Autism
• Study Start Date: April 2004
• Study Completion Date: April 2007

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

1. Autism Diagnostic Observation Schedule-Generic (ADOS-G)- Change from Baseline to Final Visit
2. Clinical Global Impression Improvement (CGI)- Change from Baseline to Final Visit
3. Aberrant Behavior Checklist (ABC) (hyperactivity/irritability sections)- Change from Baseline to Final Visit
4. Vineland Adaptive Behavior Scale- Change from Baseline to Final Visit
5. MacArthur Communicative Development Inventory (MCDI)- Change from Baseline to Final Visit
6. Conners' Parent Rating Scale-Revised: Long form (CPRS-R:L)- Change from Baseline to Final Visit

Eligibility Criteria

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

Criteria

1. Meets DSM-IV, ADI-R and ADOS-G criteria for autistic disorder
2. Age 5-17 years
3. Outpatients
4. Parent or legal guardian willing to sign informed consent.
5. Male or female patients
6. Patient scores at least a "4" (moderately ill) on the Clinical Global Impression Scale for Autistic Disorder (CGI AD).
7. Children who are minimally or non- verbal as indicated by a score of 50% of an 18 month old on the MacArthur Communicative Development Inventory

Exclusion Criteria:

1. Subjects with any of the following past or present mental disorders: psychotic disorders, mood disorders, including bipolar disorders.
2. Subjects who have displayed significant self-injurious behavior (children who have caused visible harm to themselves).
3. Subjects with active seizure disorder (seizures within the past six months).
4. Subjects with clinically significant or unstable medical illness, including patients with current evidence of clinically significant hematopoietic, or cardiovascular disease.

5. Subjects with present or history of the following:

   • gastrointestinal, liver, kidney, or other known conditions which will presently interfere with the absorption, distribution, metabolism, or excretion of drugs,
   • seizure disorders (active), cerebrovascular disease or brain trauma as etiology of autistic behavior,
   • clinically significant unstable endocrine disorder, such as hypo- or hyperthyroidism or diabetes,
   • recent history or presence of any form of malignancy.
6. Subjects who report significant improvement of autism symptoms and behaviors to current medications or have only global autism ratings on the CGI of absent, minimal or mild severity, or who are more than minimally verbal.
7. Subjects whose global autism ratings are assessed as being absent, minimal or mild.
8. Treatment within the previous 30 days with any drug known to have a well-defined potential for toxicity to a major organ.
9. Subjects with clinically significant abnormalities in laboratory tests or physical exam.
10. Subjects likely to require any other psychotropic medication during the study, with the exception of clonidine for insomnia (started at least one month prior to entrance into the study), as well as anticonvulsants at a constant dose for stable seizure disorder or, unless otherwise permitted.
11. Subjects unable to tolerate taper from psychoactive medication, if specified.
12. Subjects with a history of hypersensitivity or severe side effects associated with the use of galantamine, or other acetylcholinesterase inhibitors.
13. Subjects with a history of prior treatment with galantamine of 4mg/day for 6 weeks.

14. Subjects who have received any of the following interventions within the prescribed period before starting treatment:

    • investigational drugs within the previous 30 days.
    • monoamine oxidase inhibitors within the previous fourteen days.
    • long-acting phenothiazines within the previous six weeks.
    • other psychotropic drugs within the previous seven days, unless otherwise permitted.
15. 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.
16. Subjects who reside in a remote geographical area or who do not have regular access to transportation to the clinical facility.

Gender

Contacts and Locations

Locations

United States, New Jersey

UMDNJ Robert Wood Johnson Medical School - Dept of Psychiatry

Piscataway, New Jersey, United States, 08854

Sponsors and Collaborators

University of Medicine and Dentistry of New Jersey

National Alliance for Autism Research

Investigators

• Principal Investigator: Sherie Novotny, MD; Rutgers, The State University of New Jersey

More Information

Publications:

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Perry EK, Lee ML, Martin-Ruiz CM, Court JA, Volsen SG, Merrit J, Folly E, Iversen PE, Bauman ML, Perry RH, Wenk GL. Cholinergic activity in autism: abnormalities in the cerebral cortex and basal forebrain. Am J Psychiatry. 2001 Jul;158(7):1058-66. doi: 10.1176/appi.ajp.158.7.1058.

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Woodruff-Pak DS, Vogel RW 3rd, Wenk GL. Galantamine: effect on nicotinic receptor binding, acetylcholinesterase inhibition, and learning. Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):2089-94. doi: 10.1073/pnas.98.4.2089. Epub 2001 Feb 6.

• ClinicalTrials.gov Identifier: NCT00252603
• Other Study ID Numbers: 4682
• First Posted: November 11, 2005
• Last Update Posted: January 29, 2007
• Last Verified: January 2007

Keywords provided by Rutgers, The State University of New Jersey:

Autism; Childhood Autism

Additional relevant MeSH terms:

Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Galantamine; Cholinesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Parasympathomimetics; Autonomic Agents; Peripheral Nervous System Agents; Nootropic Agents