Clinical trial on Clinical and Immunological Investigations of Subtypes of Autism

24 Mar

The National Institutes of Health (NIH) have recently updated their webpage of featured clinical trials for autism. Many of the clinical trial recently discussed here at LeftBrainRightBrain are on that list. One that is on the featured list that I caught my eye is Clinical and Immunological Investigations of Subtypes of Autism. It is an old trial (started in 2006), but I thought it worth bringing up again.

The description is quoted below:

The purpose of this study is to learn more about autism and its subtypes. Autism is a developmental disorder in which children have problems with communication and social skills and display restricted interests and repetitive behaviors.

This study has several goals. One aim is to look at types of autism that are known, such as the regressive subtype, (where skills are lost). We will explore whether there is a unique change in immune functioning related to this subtype. Another aim is to serve as one of the sites that will pilot a larger natural history study, entitled Autism Phenome Project. The goal is to further understand autism by identifying other subtypes.

We will look at several types of medical issues that may be related to autism, including immunologic problems. Children will be followed over the course of several years. We aim to capture medical problems that may be related to autism as they develop, and study outcomes in areas such as behavior and language, in order to explore known and new subtypes of autism.

Normally developing children (aged 1) with autism (age 1, and developmental delays other than autism (age 1), may be eligible for this study.

Depending on each child’s study group and age, participants may undergo the following tests and procedures:

Baseline Visit

* Medical and developmental history, physical examination, psychological, cognitive and medical tests to assess symptoms of autism or other developmental disorders, photographs of the child’s face, collection of hair, urine and baby teeth samples. If available, hair samples from the baby’s first haircut and from the biological mother’s hair are also collected.
* Overnight electroencephalogram (EEG): A special cap with electrodes is placed on the child’s head to measure brain waves (brain electrical activity) while the child sleeps in the hospital overnight. Healthy volunteers do not undergo this procedure.
* Magnetic resonance imaging (MRI) scan: The child stays in the scanner, lying still for 10 to 15 minutes at a time. Since it may be difficult for the child to lie still, the test may be scheduled for a time when the child is likely to be sleepy, or the child may be sedated.
* Lumbar puncture (for children in the autism). This test and the MRI may be done under sedation.

Follow-Up Visits

Follow-up visits are scheduled at different intervals, depending on study group, age and aspect of the study the child is enrolled in. The visits include a short interview session with the child’s caregiver and assessment of the child’s development and behavior. Some of the assessment measures used during the baseline examination are repeated, including symptoms ratings, behavioral tests and a blood test. For some children, the final visit will include repeats of the medical procedures.

The section that jumps out to my eye: We will explore whether there is a unique change in immune functioning related to this subtype. Another aim is to serve as one of the sites that will pilot a larger natural history study, entitled Autism Phenome Project. The goal is to further understand autism by identifying other subtypes.

Yes, the NIH is looking at whether regression and immune functioning might be linked. As noted above, this study has been ongoing for some time: the trial was first listed in 2006. But, hey, I figure if I forgot about this one and found it interesting, others might be interested in this as well.

17 Responses to “Clinical trial on Clinical and Immunological Investigations of Subtypes of Autism”

  1. ebohlman March 24, 2010 at 07:24 #

    Lumbar puncture for purely research purposes????????

  2. Laurentius Rex March 24, 2010 at 08:47 #

    In one way the research will need to be done for all the wrong reasons, and that is to convince the fanatics out there that there is no “clinical” component to autism beyond that which exists for the base population.

    On the other hand it ought not to need to be done just as a sop to those who do not care a jot for ethics.

    This research is at root unethical, intrusive, and not sound. It treats autistic children as less than human, with fewer rights to withstand uneccessary medical practices including sedation for MRI never mind lumbar puncture. I bet they will not subject the NT “subjects” to the same degree of intrusive testing, if this were about pure science they would, however I guess the level of objection to that would render it impossible, therefore this research is flawed, political, and unethical in the extreme.

  3. Henrietta March 24, 2010 at 11:38 #

    Hi all,

    I’m looking for parents and sibling of a child with autism who would be happy to share their story on TV programmes such as This Morning and BBC Health from next week onwards. Do get in touch if that’s you or someone you know. my contact details are and 020 7376 6630.



  4. rose March 24, 2010 at 15:09 #

    Except for the lumbar puncture, Ben had undergone all of those as prescribed by our pediatrician, to make sure there was no other medical reason for his difference.

  5. Emily March 24, 2010 at 16:16 #

    NOT a fan of the LP for research.

    • Sullivan March 24, 2010 at 17:02 #


      I’m with you on this. Lumbar punctures are pretty extreme for an investigational study. I would not have enrolled my kid in this study, and I suspect the LP’s are a big reason why this study is still recruiting 4 years later.

      I post this to point out that the government is funding exactly the sort of research some groups call for. You wouldn’t know that from what those groups say. Quite the opposite. Their public stance is that the government doesn’t support them.

  6. Ian MacGregor March 24, 2010 at 19:31 #

    Is not an LP involved in a check for mitochondrial disease? I suspect that’s what’s being done here. I would hope there were strong indications of its presence before the LP was performed. I would not have my daughter participate in a trial were LP’s were done without medical cause.

    I don’t see anything wrong with the steps taken to obtain an EEG over several hours. The group of neurotypical children are not subject to it as we know what a normal EEG looks like. Do we have enough data about brains of children with autism. I think not. There is the potential that the sedative may affect the EEG, but whether this is truly a factor, I don’t know.

  7. dr treg March 24, 2010 at 20:09 #

    “Recent reports implicating elevated cytokines in the central nervous system in a small number of patients studied with autism have reported clinical regression. These studies have not focused on tumor necrosis factor-alpha as a possible marker for inflammatory damage. A series of 10 children with autism had clinical evaluation of their serum and spinal fluid for inflammatory changes and possible metabolic disease as part of their neurological evaluation. Elevation of cerebrospinal fluid levels of tumor necrosis factor-alpha was significantly higher (mean = 104.10 pg/mL) than concurrent serum levels (mean = 2.78 pg/mL) in all of the patients studied. The ratio of the cerebrospinal fluid levels to serum levels averaged 53.7:1. This ratio is significantly higher than the elevations reported for other pathological states for which cerebrospinal fluid and serum tumor necrosis factor-alpha levels have been simultaneously measured. This observation may offer a unique insight into central nervous system inflammatory mechanisms that may contribute to the onset of autism and may serve as a potential clinical marker. More controlled study of this potentially important observation may prove valuable.”
    Perhaps immunological studies of CSF are important in discovering more about the immune abnormalities in autism.

  8. Sullivan March 24, 2010 at 20:44 #

    Ian MacGregor,

    LP’s are sometimes used for mitochondrial disorder checks, as I recall.

    Sedatives can have an effect on EEG’s, I believe. I think that they try to avoid sedatives when doing EEG’s checking for epilepsy.

  9. passionlessDrone March 24, 2010 at 22:00 #

    Hello friends –

    Great news!

    The lumbar puncture issue is a sticky one. This strikes me as a big problem, our very limited dataset on the CNS in autism has a lot of evidence for immunological problems, but getting enough tissue is difficult if our goal is to identify phenotypes.

    The Chez paper from 2007 finding tnf alpha in the CNS was a good example of these problems. They only had a few kids (10), and their population was children that were having punctures for other problems that also happened to have autism. As a result of the relative lack of ‘normal’ CSF to use as controls, the authors used ranges from other diseases for controls, such as Alzheimer’s, and wound up with findings that were problematic to put into context.

    On the whole, I am very pleased that the NIH has deemed the immunological angle of sufficient importance to initiate this study. Had this been posted a year ago, I might have tried to enroll Luke.

    Thank you for posting this, Sullivan.

    – pD

  10. Mike Stanton March 25, 2010 at 00:55 #

    This study is nothing more than an attempt to prove that there is a s distinct form of regressive autism that can be distinguished from non-regressive autism by altered immune response, raised cytokine levels and MRI evidence of brain imflammation. Originally they were going to carry out lumbar punctures on non-autistic children with developmental delay and Retts children as well but that has gone.

    I also note that they have been recruiting children between 12 and 48 months for the last 48 months. So presumably the first children recruited are no longer eligible for a study that we can only hope will never be done.

  11. Laurentius Rex March 25, 2010 at 01:24 #

    And once again I have to state the position in advance that will be discovered (and don’t ask me how I am so certain, just hang around and you will see for yourself) that there is no regressive autism, because developmental trajectories do not proceed in an orderly fashion even for neurotypical (so called healthy) subjects.

    It’s the teleological fallacy innit, the developmental variant of the Whig version of history.

    If you know English country roads you will know that in order to get to a particular village on the backroads you might well find yourself at some point travelling away from it as the crow flies.

    I am not sure if everyone reading will understand the analogy, but some degree of apparant regression is actually part of “normal” development in that skills aquired early are apparantly lost, but lost is not the right word really as it is a matter of submergence rather than loss.

  12. Rose March 25, 2010 at 02:10 #

    I lived in fear that Ben would “regress” or lose ALL the language he had. You say, “don’t ask how I am so certain”…so I won’t.

    I must say that fear of regression drives a lot of parents to do as much as they can while the child is young, in order to avoid it. Personally, I have never noticed “regression” in Ben, only growth. But I’ve heard parents stories, or read about them.

    What you propose is interesting because it lessons the d-r-i-v-e to whip our kids into shape, less they lose what they have. It also leads away from a biological “poisoning” caused by the bodies maladaptive response to chemicals typically harmless in small degrees but teratogenic in buildup. (phenlyalinine, copper, etc.)

    Sorry, I”ve got to get off the web…

  13. Ian MacGregor March 25, 2010 at 02:26 #

    Regression is common in autism because the disorder does not manifest itself fully until sometime after birth. My daughter lost her ability to communicate. Before she had the ability to make simple verbal requests, recognized letters of the alphabet, colors, and the names of nearly everything an 18 month to two-year old encounters. All that was lost. Her autism was there from birth, lack of eye contact, she never developed any social language or gestures, nor did developing any social binding to us.

    Many of these things through time and love she has recovered except, she still cannot communicate, and remains intellectually challenged.

    This is not a normal development pattern. Many autistic children suffer regression, and then recover to become high functioning. One cannot predict the outcome from the amount of skills lost, except while the children who are due to become high-functioning are making strides towards that outcome, the low-functioning children are often still regressing. When things turn around, their gains are much slower much less complete.

  14. Ian MacGregor March 25, 2010 at 15:23 #

    I wanted to amplify my comments about my daughter. We use a program called TeachTown, it is a subscription ABA type program. There while working with my wife our daughter can point to different colors and things with some degree of accuracy. Her ability fluctuates from session to session, but in the main she gets things right. She has shown no ability at home to do this when not using TeachTown, but some ability at school.

    TeachTown has been a wonderful tool in building the relationship between my wife and daughter.

    Last week at Sunday school after they were done with the craft, which is really done by her aide, my daughter returned to the table and made some scribbles on a piece of paper with a crayon all on her own. This would not thrill many parents of a nearly 13-year old, but for us it was huge.


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