Sometimes wishing does not make it so.
Parents of autistic children began calling Melvin Heyman, MD, chief ofpediatric gastroenterology at the University of California, San Francisco in1998. They were full of hope about reports that secretin, a hormone produced inthe intestines and used in a diagnostic procedure, might improve their children's ability to talk and interact with others. To test that concept, Heyman andclinical research fellow Jenifer Lightdale, MD, teamed with autism experts fromUCSF's Langley Porter Psychiatric Institute to perform objective tests oflanguage and behavior before and after administering secretin.
The results were reported May 13, 2000 at the Pediatric AcademicSocieties/American Academy of Pediatrics meeting in Boston. Twenty autisticchildren, aged 3-6, received formal language testing before infusion withsecretin and in four follow-up tests in ensuing weeks. No child showedsignificant changes in either receptive or expressive language.
"Beginning in 1998, a worldwide storm of reports on the internet, plus storiesin the Wall Street Journal and on Dateline NBC, have described secretin aspotentially a true treatment for children with autism," said Lightdale. "Ourstudy and one other were the first to test objectively whether this was so. Webegan the study because we were concerned that parents and health careproviders did not have sufficient scientific information to evaluate secretin'spotential effects."
Both studies had negative results. However, the researchers reported that someparents from both study groups indicated they still would use the drug fortheir children.
Lightdale conducted the UCSF study under Heyman's supervision. Theirco-investigators were UCSF-LPPI autism experts Bryna S. Siegel, PhD, Glen R.Elliott, MD, PhD, Cathy Hayer, MA, and Christopher Lind-White, MD. Lightdale isnow a postdoctoral fellow in pediatric gastroenterology at Children's HospitalBoston.
Heyman said that parents' excitement about secretin were first stirred by 1998stories of a mother who said that her son showed improvements in autisticsymptoms after he was given secretin during a diagnostic test for diarrhea.Dateline NBC profiled the mother and her son. The Wall Street Journal describedan entrepreneur, the father of two autistic children, who founded apharmaceutical company and obtained the license for synthetic secretin toensure a supply of the drug to treat autism. An article in the Journal of theAssociation of Academic Minority Physicians described the first boy, as well astwo other children who reportedly showed increased alertness, eye contact andexpressive language within days after receiving a single dose of the hormone.The article described marked improvements in language over a short time, andreported effects lasting up to five weeks.
"After word of these observations spread, UCSF's gastrointestinal service wasinundated with calls from parents asking for secretin infusions, often as manyas 30 per day," Heyman said. Eventually, more than 2,000 called from NorthernCalifornia and around the country. "The need for research to see whether thedrug was effective was accentuated by reports from autism interest groups thatthousands of children had begun receiving secretin in repeated doses," Heymansaid. Some web entrepreneurs charged inflated prices to give secretin toautistic children. In some cases the drug was administered in unproven ways,such as by mouth or through the skin using a solvent called DMSO.
Siegel, who is associate adjunct professor of psychiatry at UCSF, has workedwith autistic children and their families for 25 years. She defined autism as asyndrome that begins in the first few years of life, involving severe deficitsin social and communication skills. It affects the child's ability to processincoming information from the social and physical worlds, to interact withothers and to use language. The cause is not known and, to date, there is noproven cure. However, for some autistic children, behavioral interventions canmarkedly improve language and social skills. For older individuals, medicationssometimes can help ease obsessive behaviors.
Heyman said that secretin is a hormone that stimulates the pancreas to increaseproduction of digestive fluids. It is approved as a diagnostic drug, to showwhether the pancreas is impaired in its ability to respond to stimulation,since that can cause chronic diarrhea and other disorders. Secretin has noknown therapeutic use, and few known side effects, though one version of thedrug has been associated with allergic and anaphylactic reactions. It has notbeen tested for safety or efficacy in children, either in a single-dose or as along-term medication.
Lightdale's study looked at autistic children who were near the same age andwere given a similar intravenous dose of secretin to the three childrendescribed in the 1998 journal article. Each child in the UCSF study was testedbefore the infusion with secretin and again in sessions one, two, three andfive weeks after infusion. Each child was given a standardized test called thePreschool Language Scale - 3, and was videotaped during play and scored forspecific behaviors characteristic of autism.
The PLS-3 test was objectively scored and indicated no quantifiable changeseither in the way children understood language, or the way they were able touse words and gestures to express themselves. The videotaped behavior testswere scored using criteria in the test manual, by three independent reviewerswho never met the children and were not told which week of the study a giventest represented. The latter results will be published at a later date.
A true, dramatic change in skills and behavior would have been a surprisingresult after a dose of a drug, said Siegel. "The claims made for this drug donot hold up well to any neuro-developmental model of how new skills areacquired," she said. "Language ability depends on changes in the brain as thechild goes through activities that stimulate the acquisition of vocabulary andgrammar structure. The child has to develop a two year old's language abilityto go on and learn to speak like a three year old. A pill can't do that forhim."
Eighteen sets of parents in the study filled out a survey afterwards abouttheir child's condition. In contrast to the results observed by the studyauthors, 15 sets of parents indicated that they felt their child had moderateto significant improvements in language skills following the secretin infusion.
The UCSF results are similar to those of another study, reported in December,1999 in the New England Journal of Medicine, by researchers at the Universityof North Carolina. They studied children aged 3 - 14 who had either autism or asimilar condition, pervasive developmental disorder. They administered secretinto half and placebo to the rest. The UNC researchers found no significanteffect of secretin - in fact, the children who received the placebo showedslightly greater improvement on behavior tests. However, a majority of parents,including those whose children received placebo, retained their interest inusing secretin even after they were told the results.
How to explain the difference between objective test scores and parents'perceptions? "This is a very good example of placebo effect," said Siegel. "Bydefinition, the placebo can be expected to cure whatever ails you. In thestudies of secretin, these parents saw differences in eye contact, inattention, in use of words - any activity that seemed like an improvement wasattributed to the drug."
"Hope is essential when you care for a child with a chronic disability andthere is no definitive treatment," Siegel said. "But sometimes hope lets peoplebelieve more than they truly can count on. It can be a roller-coaster that, inthe end, is just another source of strain."
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