Effects of Hyperbaric Oxygen Therapy on Children With Autism
Condition: Autism
MeSH terms: Autistic Disorder
Study type: Interventional
Phase: Phase 1

Summary: 
      PURPOSE

      The purpose of this investigation is to evaluate the cognitive and behavioral effects of
      Hyperbaric Oxygenation Therapy in children who present with a diagnosis of autism spectrum
      disorder.

      HYPOTHESIS

        1. Hyperbaric Oxygenation Therapy will be safe to use with children with autism.

        2. Hyperbaric Oxygenation Therapy will have a statistically significant effect on the
           symptoms of autism.

        3. Hyperbaric Oxygenation Therapy will have a clinically significant observable effect on
           the overt symptoms of autism.

        4. The decreases in the symptoms of autism will correlate positively with the number of
           Hyperbaric Oxygenation Therapy sessions.

        5. Treatment gains obtained from Hyperbaric Oxygenation Therapy will be maintained at
           follow-up, post 40 treatment sessions.

      SPECIFIC AIMS

        1. Provide further evidence for the safety of Hyperbaric Oxygenation Therapy in children
           with autism.

        2. To quantitatively assess the effects of Hyperbaric Oxygenation Therapy on behavioral and
           cognitive symptoms of autism before, during, and after treatment.

        3. Identify number of treatments required to reach therapeutic effects.

        4. Identify the length and durability of treatment effect and maintenance.
    

Detailed description: 
      Participants & Setting

      Participants in this study will be 30 consecutive children referred to Thoughtful House for
      the treatment of autism or a related developmental disorder. Participants may or may not also
      be concurrently receiving intensive behavioral intervention services from the Center for
      Autism and Related Disorders. All therapy and behavioral testing sessions will occur on the
      premises of Thoughtful House.

      Inclusion Criteria

      The following criteria will be considered inclusionary:

        -  Male and female children 2-10 years diagnosed with autism, PDD, or Aspergers

        -  No anticipated changes in treatment for the study duration (e.g., diet, nutrients)

             -  No additional biomedical treatments started 6 weeks prior to enrollment

             -  No changes in dietary management for 3 months prior to enrollment

        -  Access to Thoughtful House on a daily basis, or as necessary for the study participation

      In addition, the child participant must be:

        -  Ambulatory or require minimum support walking, per parent

        -  Able to sit still for 5 minutes or longer with a preferred toy item, per parent

        -  Adequate vision and hearing for the purposes of test administration, per parent

        -  Adequate arm-hand-finger coordination (i.e., able to point) for learning and cognitive
           tasks used in outcome measurement, per parent

        -  Stable and controlled medical disorder

        -  Under the care of a caregiver willing to participate by attending regularly scheduled
           appointments and completing the necessary measures

      Exclusion criteria

      The following criteria will be considered exclusionary:

      Current otitis media Sinus infection Asthma Pulmonary cysts Emphysema Upper respiratory
      infection Severe claustrophobia, intolerance to being in the chamber History of Seizures
      Unstable/uncontrolled disorder of any kind

      Design Ten sets of multiple baseline measurement groups, 3 participants each (n=30) will be
      used to evaluate the effects of HBOT on the behavioral measures of adaptive (mean length of
      utterance, MLU), aberrant, and stereotyped behaviors. The first participant in each multiple
      baseline will receive sessions of the behavioral measures for a minimum of one week prior to
      the implementation of HBOT. Subsequent participants cannot receive HBOT until an effect is
      observed (as determined via visual inspection and statistical analysis of the data) on prior
      participants or until prior participants have received 40 HBOT treatments, whatever occurs
      first. Subsequent to receiving 40 HBOT treatments, each participant will be given a break
      from HBOT for at least one week, during which time the schedule of behavioral measures will
      remain the same. If proficiency on the behavioral measures decreases when HBOT is terminated
      for one week, HBOT may be reinitiated as per the discretion of the physician and parent.

      HBOT Systematic Desensitization

      Because children with autism often do not tolerate changes in the environment, we anticipate
      difficulties with initial treatment compliance in some children. In a clinical setting,
      children become acquainted with the mask and machine, and are introduced to an enclosed
      oxygen chamber and HBOT begins at a prescribed pressure. Below are the general
      desensitization procedures for the participants:

        1. The child is introduced to the mask and therapist models how it is worn

        2. The child is required to hold the un-strapped mask loosely against his/her face until
           he/she can breathe while holding the mask in place for a minute or more

        3. The child is required to strap the mask on for a minute, with gradual increase to 30+
           minutes

        4. The child is seated upright in the chamber with the mask on and the HBOT machine off for
           a minute, with a gradual increase to 30+ minutes

        5. The child is lying down in the chamber with the mask on and the HBOT machine on at a low
           pressure setting for a minute, with gradual increase to 30+ minutes

        6. The child has the mask strapped on and lying down, while the HBOT is running for an hour

      For some children who exhibit severe noncompliance with the HBOT procedure, relaxation
      training and listening to preferred music prior to the HBOT procedure may be used.

      In order to minimize the influence of learning and attention from parents/therapists during
      HBOT/placebo sessions, all children will be viewing a developmentally-appropriate DVD (e.g.,
      Disney movie) during all HBOT sessions to minimize confounding effects that may occur with
      other activities. The viewing of DVDs will continue throughout all 80 sessions and during
      follow-up.

      Procedures Data will be collected according to the following schedule: prior to treatment,
      following 5, 15, 25, and 40 HBOT treatments, as well as at post-treatment and 1 and 3-month
      follow-up.

      Behavioral Measures Participants who are receiving intensive behavioral intervention services
      during the course of the study will have continuous measures of many aspects of performance
      recorded daily, as a part of their behavioral intervention services. Such measures will be
      customized to the behavioral education needs of each child, but are likely to include, at a
      minimum: 1) measure of adaptive behavior (e.g., language); 2) measure of aberrant behavior
      (e.g., tantrums, etc.); and 3) stereotyped behavior. All such continuous measures can be
      observed throughout the course of the participant's involvement in the study. However, the
      consideration of any particular continuous measure as part of the current study would require
      inter-observer agreement data be collected on those measures for a minimum of 25% of the
      observed data. That is, a second, independent observer must record data on all behavioral
      clinical measures which will be included in the study. Participants who are not receiving
      intensive behavioral intervention services will receive only the behavioral measures
      described below. Participants who are receiving intensive behavioral intervention services
      during the course of the study will receive the measures described below, as well as any of
      their clinical behavioral measures for which adequate inter-observer agreement data are
      collected.

      Repeated acquisition task

      A defining feature of autism is a global impairment in one's ability to learn. Repeated
      acquisition tasks are commonly used in drug behavioral pharmacology studies to assess the
      effect of a drug on the ability of an individual to learn, that is, the efficiency with which
      the individual's behavior is brought under new forms of stimulus control. Repeated
      acquisition tasks typically involve the participant learning to respond to a new sequence of
      positions during each session. For example, four levers or buttons are presented and the
      participant must press the four buttons in a particular sequence in order to earn
      reinforcement. However, the correct sequence is different for every session, and typically
      one session is conducted daily, so the sequence of responding required to earn reinforcement
      is different each day. The performance of the participant can be analyzed in a number of ways
      including the percent correct for the entire session, the total number of responses or the
      number of errors made until 80% correct responding is reached.

      The complexity of the task can be adjusted by varying either or both of two parameters: 1)
      the number of response positions present (e.g., number of buttons present), and 2) the number
      of responses in the sequence required for reinforcement. For example, ten buttons could be
      present but the participant is only required to press one particular button out of the ten in
      order to get reinforcement, versus pressing a sequence of ten which involves each button
      once, versus having only two buttons present, etc. The standard degree of complexity in
      behavioral pharmacology research is having four response options present and requiring the
      participant to respond to all four in a particular order to earn reinforcement.

      Delayed matching to sample

      An additional cognitive process that might be of interest when evaluating HBOT is short-term
      memory. A common behavioral measure of short-term memory is a delayed matching-to-sample
      (DMTS) procedure. In such procedures, a sample stimulus is presented and then removed and a
      delay occurs between the removal of the sample stimulus and the presentation of two or more
      comparison stimuli. The participant earns reinforcement for choosing the correct comparison
      stimulus. The delay between the removal of the sample stimulus and the presentation of the
      comparison stimuli can vary from zero to any conceivable duration, but typically does not
      exceed 60 seconds.

      The relation between the sample stimulus and the correct comparison stimulus can be varied in
      order to alter the difficulty of the task. For example, the sample stimulus and the correct
      comparison stimulus may be identical, often referred to as "identity matching." This is the
      easiest form of DMTS. Alternatively, the sample stimulus may be related to the correct
      comparison stimulus in an abstract dimension. For example, the sample stimulus may be the
      written word car and the correct comparison stimulus might be a bicycle, with a gorilla and a
      fork as distracters.

      Sessions can be conducted with a fixed delay or the delay can be systematically increased
      during the session in order to identify a threshold at which the participant is no longer
      able to respond correctly. For example, on the first trial, the delay may be zero second and
      then the delay may be increased by 4 seconds on each subsequent trial, contingent on correct
      responsse on the previous trial. The data are then analyzed to determine the longest delay at
      which the participant was consistently correct at 80% accuracy. This threshold can be
      considered a measure of the participant's short term memory at the time of the session.

      Standardized Measures

      In addition to the direct measures of behavior described above, standardized intelligence and
      adaptive assessments will be conducted prior to the initiation of HBOT. These will include:

      ADI/ADOS WPPSI-III (2-6 years) /WASI (6+ years) Vineland Adaptive Behavior Scale (VABS)
      Subjective Questionnaires Aberrant Behavior Checklist Clinical Global Impression ATEC
      Selected sections of the APEQ BRIEF Parenting Stress Index Repetitive Behavior Scale A side
      effect questionnaire Thoughtful House Caregiver diary

      Laboratory & Physiological Measures Full physical exam (weight, height, vital
      signs-temperature) Otoscopic examination prior to enrollment in the study

      STATISTICAL DESIGN/ANALYSIS

      The primary measures will consist of changes in the rate and percentage of change from pre
      and post HBOT adaptive, aberrant, and stereotyped behaviors.

      ADVERSE EFFECTS AND MANAGEMENT: the only 2 most commonly encountered adverse reactions are
      ear pain and sinus pressure.

      Ear Pain: This can be minimized or ameliorated by working on pressure equalization techniques
      across the tympanic membrane. These techniques include:

      Yawning Drinking water/juice Val Salva (Plugging nose and mouth, blowing air out the ears)
      Jaw thrust and swallowing Bending head to the side and yawning/swallowing. The technician can
      slow the rate of pressurization allowing adequate time for pressure equalization to occur

      Sinus pressure: this can be ameliorated with slowing down the rate of pressurization and
      depressurization. Also, the administration of 0.5% Neosynephrine intranasally and
      pseudoephedrine can be used.

      Should a serious adverse event occur, the form SERIOUS ADVERSE EVENT REPORTING FORM will be
      filled out and reported to the IRB office within 5 business days and a written summary of the
      circumstances surrounding the adverse reaction be submitted to the IRB for review at the next
      scheduled IRB meeting.

      Minor reactions, such as ear pain or sinus pressure will be managed and documented by the
      physician.
    

Intervention name(s): Hyperbaric Oxygen Therapy
Intervention type(s): Device
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Autism; Hyperbaric Oxygen Therapy; Behavioral assessments