Secretin has been claimed to transform some autistic children, improving many of their symptoms within a week. Although it is not licensed for treating the disease, thousands of children are believed to have received it after their parents obtained it through the Internet and sympathetic doctors. But researchers announced yesterday that they had conducted a double-blind, placebo-controlled trial which found no improvement in those children given the drug. Now they say that secretin "should be avoided as a treatment for autism until more information is available".
Autism in children is a heartbreak to parents...and a puzzle to researchers. Recently, reports of a so called cure have surfaced, involving a drug called secretin. But, in a small study published today, the promise of secretin is questioned
Secretin is a neurotransmitter in the neuropeptide group. It is one of the hormones that controls digestion. It is a polypeptide composed of 27 amino acids and is secreted by cells in the digestive system when the stomach empties.
Pervasive Developmental Disorders (PDD) are chronic, lifelong disorders for which there is as yet no effective cure, and medical management remains a challenge for clinicians. The current report describes two patients affected by autistic disorder with associated gastrointestinal symptoms. They received multiple doses of intravenous secretin for a six-month period and were assessed with several specific outcome measures to evaluate drug effect. The administration of secretin led to some significant and lasting improvement in only one case. Gastroesophageal reflux may contribute to some of the behavioural problems and explain the effect of secretin since its suppressive effect on gastric secretion is well known. It is also true that autistic children with gastroesophageal reflux and a higher IQ could constitute a subtype which responds to secretin administration and that could be labelled as a "gastrointestinal subtype".
This study confirms the outcome of multiple other double blind, placebo controlled studies of the lack of efficacy of secretin in changing core symptoms of autism. Despite the extensive documentation of the lack of efficacy, reports on the Internet and demand for treatment with secretin still exist, including intravenous, transdermal, and sublingual administration.
In a double blind crossover setting, the ability of parents of young children with autism to distinguish secretin from placebo was no greater than chance. Most parents based their guesses on perceived improvement following one infusion or the other; a minority based their guesses on perceived deterioration.
The need and the beneficial response to secretin are dependent upon the amount of damage to the duodenum and upper small intestine from whatever cause, and on the stomach's ability to produce adequate hydrochloric acid (HCl) for proper digestion.
SA crosses the vascular barrier by a nonsaturable process and the choroid plexus by a saturable process in amounts that for other members of its family produce central nervous system (CNS) effects. This passage provides a pathway through which peripherally administered SA could affect the CNS.
There was no evidence for efficacy of secretin in this preliminary randomized controlled trial. These data were collected as part of a multicenter study with the University of California-Irvine and the University of Utah.
With a total study completion rate across all participants of 96%, repeated measures analyses of variance revealed no significant increases in children's language skills from baseline across all 5 study time periods after a single infusion of secretin. Similarly, neither significant decreases in atypical behaviors nor increases in prosocial behaviors and developmentally appropriate play skills emerged. Furthermore, no relationship was found between parental reports of change and observable improvement in the sample.
The agent bought two vials of a substance labeled "Secretin Powder," syringes and hypodermic needles from a Little Angels office manager who was not a licensed physician or pharmacist. An analysis of the substance found no detectable level of secretin...
Various letters and articles on secretin
Twenty-five established standardised outcome measures were reported to assess core features of autism, communication, behaviour, visio-spatial skills, affect and adverse events within fourteen included studies. No more than four studies used any one outcome measure similarly. Outcomes were reported between three and six weeks. RCTs of efficacy of secretin in autism have not shown improvements for core features of autism. There is no evidence that single or multiple dose intravenous secretin is effective and as such it should not currently be recommended or administered as a treatment for autism. Further experimental assessment of secretin's effectiveness for autism can only be justified if methodological problems of existing research can be overcome.
Previous trials of secretin for the treatment of autism have utilized a single or double dose administered intravenously. This is a report of a double-blind, randomized, controlled crossover trial of transdermally applied secretin in 15 children diagnosed with autism or pervasive developmental delay. Secretin or placebo was applied daily, in ointment form, to the backs of the children in randomized, successive 4 week periods with an intermediate 6 week washout period. Behavioral outcomes were measured by parents and teachers using the Autism Treatment Evaluation Checklist. Overall, there were no statistically significant differences in speech, sociability, sensory, and health scores for treatment versus placebo periods. In addition, there were no differences in such scores for children with a history of diarrhea. Severity of autism was significantly greater at baseline in children receiving concomitant medications. Improvement in speech was found during the treatment phase of the trial (p = 0.0479 for secretin versus placebo) only in children not using other medications.
There were no group differences on formal measures of language, cognition, or autistic symptomatology. Subgroupings based on cognitive level, the presence or absence of diarrhea, or a history of regression failed to show any significant therapeutic effects of secretin.
By giving a small dose of Secretin every day ( as opposed to an injection once a month ) we imitate the normal production of Secretin and have observed that the effects are better.
There are theoretical concerns re that even if one screens for antibodies appropriately, repeated infusions could trigger a child's immune system to attack their own Secretin (or its receptors) creating major medical problems.
My contribution has been to state what I believe to be true and I am proud to say that most of the time I think that many of the things I said which were unpopular at the time, have turned out to be true.
Receptors for Secretin are present not only in the pancreas, but in the human brain as well. In particular, they are found in the hippocampus, an area of the brain which is associated with memory and learning.
Secretin stimulates the pancreas to release bicarbonate and digestive enzymes into the intestinal tract, and stimulates the liver to excrete bile and the stomach to produce pepsin.
In some cases where the patient was on the autistic spectrum, amelioration of the targeted physical problems was accompanied by improved social and language skills.
As the genetic blueprint for human development continues to unfold, we can look at the distribution of genes for secretin-like molecules and receptors in the chromosomes and relate them to cell types and developmental pathways.
In a letter to the Wall Street Journal, seven professionals who had autistic children expressed concerns that (a) since injectable secretin is extracted from pig intestines, repeated doses might cause the body to make antibodies to secretin; (b) smaller protein fragments in secretin preparations might trigger immune reactions; (c) the amino acid cysteine, which is used to stabilize the preparations, could cause other adverse effects.
Secretin is a polypeptide hormone involved in the regulation of gastric function. Following administration by intravenous injection, it causes an increase in the secretion of the pancreas of water and bicarbonate into the duodenum.
There was no evidence that either biologic secretin or synthetic secretin demonstrated an amelioration of symptoms beyond that observed in the placebo groups, the authors concluded.
The intestinal hormone secretin, considered by some to be a promising drug in the treatment of autism, does not improve the symptoms and should not be used to treat the disorder, according to a new review of studies. After analyzing data from 14 high-quality studies involving 618 patients with autism disorders, Dr. Katrina Williams of the Children's Hospital at Westmeade, Australia, and colleagues found no evidence that doses of intravenous secretin improve the social, behavioral or communication problems associated with autism. Secretin "should not currently be recommended or administered as a treatment for autism," the reviewers conclude. There were no serious side effects reported in any of the studies, but "more adverse events are likely to be reported if secretin is made widely available," Williams says.
A number of controlled clinical trials did not show improvement in autistic symptoms with secretin compared with placebo, possibly indicating no role for the drug in autistic disorder.
The bottom line is that secretin, during its relatively brief bioactive existence, must somehow switch on sustained production of something that sustains the behavioral change.
Finding a physician who will infuse secretin (a 2-minute job) is therefore a problem. Another problem may be the availability of secretin.
Both animal-derived and synthetic forms of the hormone have failed to demonstrate superiority over placebo in other controlled trials investigating its efficacy in ameliorating the core symptoms of autism.
Statements issued by the Albany Medical Center, National Institutes of Health, University of Rochester, NYAN Eastern Regional Center Information
Without adequate HCl, secretin infusion can, at best, be only partially effective in restoring digestion and proper physical and mental function. With proper HCl present, secretin infusion may be totally unnecessary.