Randomized Controlled Trial of a Gluten Free Diet In Patients With Schizophrenia Who Are Gliadin-Positive

Out of 300 million persons in the United States, about one-half of one percent, or 1.5
million, have a diagnosis of schizophrenia. Schizophrenia begins in young adulthood, and
often is chronic and disabling for the remainder of the life course], which is shorter than
for the general population by as much as 25 years. The costs of schizophrenia in the United
States are estimated to be between $30 and $60 billion dollars annually. Treatment for
schizophrenia is only marginally successful: in the Clinical Antipsychotic Trials of
Intervention Effectiveness (CATIE), for example, the medication prescribed at the beginning
of the trial was stopped or changed in nearly 75% by the completion of the trial 18 months
later. The medications have limited effect on negative symptoms or cognitive impairments of
schizophrenia, and many have severe and permanent side effects. The basic hypothesis
underlying treatment for schizophrenia has not changed for more than half a century. New
treatments are needed.

Much accumulating evidence suggests that sensitivity to gluten may be related to symptoms or
etiology in schizophrenia and that gluten free diets may lead to significant symptom
resolution, but only in patients who are known to have antibodies to gluten.

Gluten sensitivity may be more common than thought and stems from a different etiology and
symptom presentation than Celiac Disease. The investigators analysis of the CATIE sample
show that about 23% of persons with schizophrenia (compared to 3% of healthy controls) have
Gluten Sensitivity (about 300,000 persons in the United States) through the identification
of gliadin positive antibodies in their blood. The investigators hypothesize that people
with this biomarker could have robust symptom improvements with the removal of the antigen
from the diet (gluten). If only half of people with schizophrenia and these antibodies were
to substantially benefit from removal of gluten from the diet, as in the case studies and
with certain subjects in the clinical trials, this would provide a new transformative
treatment option for an identifiable subpopulation of people with schizophrenia and would be
of enormous benefit to patients, families and society. Another benefit to the public's
health from this study will be enhanced knowledge of the etiology of schizophrenia,
including possible linkages between neuropsychiatric disease and immune system activation,
and identification of novel, immune-linked treatment targets.

The results of this research could lead to screening for Anti-Gliadin Antibodies early in
life or at the first episode of schizophrenia, as recommended by some already. Screening
involves financial and emotional costs, and better evidence is needed before this
recommendation can be justified. Moreover, a new treatment paradigm of removing gluten from
the diet by means of gluten blocking medications (already in early study) could advance
treatment significantly.

This study will test the efficacy, in a pilot fashion, of 20 participants in a double blind
five week randomized placebo controlled gluten free diet vs identical diet with gluten in
gliadin-positive individuals with schizophrenia. Approximately equal numbers will receive
the addition of gluten, or non-gluten starch, in identical form (given as flour in food).
The investigators plan to develop mechanisms and procedures to locate, screen, and recruit
subjects into the inpatient intervention study, retain them during the inpatient phase. Once
admitted baseline assessments may take approximately a few days but will be mostly completed
in the first week prior to the 5 week randomization, thus patients may stay longer than 5
weeks. At the end of the double blind trial the investigators will prepare for discharge and
then test the feasibility of successfully maintaining gluten free diets after the
intervention phase is complete, for at least two months.