Effects of Hyperbaric Oxygen Therapy on Behavioral Measures of Short Term Memory, Learning, and Behavior in Children With Autism
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.
Condition:
Autism
Treatment:
Hyperbaric Oxygen Therapy
Start Date:
November 2006
Sponsor:
Thoughtful House
For More Information:
https://clinicaltrials.gov/show/NCT00406159