Galantamine Versus Placebo in Childhood Autism
Galantamine Versus Placebo in Childhood Autism
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.
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.
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