Cromoglycate Adjunctive Therapy for Outpatients With Schizophrenia

Schizophrenia (SZ) extracts a heavy personal and public health cost, primarily because there
is no effective treatment. Though many drugs are currently available, the majority provide
only partial relief for psychotic phenomena and none guarantee more than modest relief for
'negative symptoms' or for cognitive impairments. The Investigators must search for
additional effective and safe medications. Recently, big data analytic strategies have
yielded numerous 'repurposed' drugs, i.e., drugs with new indications that are already
licensed for other uses. These strategies utilize massive data bases of known drug effects to
find candidates that could predictably counteract known pathogenic effects of the disorder in
question. Repurposed drugs are appealing not only because they have already been marketed and
have known side effect profiles, but also because they have increased prior probability of
efficacy. Still, careful randomized controlled trials (RCTs) are necessary for the new
indications. The investigators have designed a systematic search for repurposed drugs likely
to be beneficial for patients with SZ. Our novel search strategy began with the construction
of a comprehensive protein-protein interaction network (PPI) for SZ using a validated method.
Next, The Investigators searched public data bases for drugs that have predicted effects on
multiple proteins in the SZ PPI network, but opposite to those observed in patients with SZ.
The initial list was pruned using predetermined criteria, leaving 7 drugs of which
cromoglycate (CGY) had the best negative correlation score. Reassuringly, three other drugs
with lower scores in our list have already been tested for SZ. CGY is a safe and highly
effective mast cell inhibitor that has been licensed for over 25 years for prophylaxis of
asthma and allergies; it is also used to treat systemic mastocytosis and ulcerative colitis.
Independent of our research, CGY is also predicted to stabilize the blood brain barrier
(BBB), which can be disrupted in patients with SZ. Animal studies and favorable Log P
estimates assure that CGY can cross the BBB. CGY has few reported side effects, despite its
extensive use. Thus, multiple factors motivate our RCT. The Investigators propose a double
blind adjunctive RCT for SZ using CGY. To maximize therapeutic benefits while minimizing risk
and discomfort, The Investigators will enroll outpatients with SZ who meet criteria for
residual positive symptoms after adequate trials of standard antipsychotic drug (APD) therapy
(N=100, total). The Investigators will prefer patients in the early course of their illness.
CGY or placebo will be added to prescribed medications for 4 weeks utilizing the Sequential
Parallel Comparison Design to maximize power. The primary outcome will be improvement in
positive symptoms as determined by the Positive and Negative Syndrome Scale (PANSS) positive
symptom subscale. Secondary outcomes include total symptoms (PANSS total score), negative
symptoms (PANSS negative symptom scale scores), cognition (Penn Computerized Neurocognitive
Battery), and social function. Serum CGY levels will be monitored. The Investigators have
proven experience with RCTs and the large number of patients are our clinical service ensures
that recruitment targets will be fulfilled.

Inclusion Criteria:

- Written informed consent.

- Both genders, ages 18-60 years

- Schizophrenia / schizoaffective disorder (DSM V).

- Treated with the same APD for at least 60 days; Stable dose of APD for > 1 month,
continued throughout the study.

- PANSS total score of 60 and Score 4 or more on one or more items of the 'positive'
syndrome items (P1-P7)

- Preference for patients with duration of psychosis less than 7 years.

Exclusion Criteria:

- Substance abuse in the past month/dependence past 6 months.

- History or current medical /neurological illnesses that may lead to an unstable
course, e.g., epilepsy.

- Pregnancy.

- History of immune disorders, HIV infection, or receiving immune-suppressants or
immuno-modulators, e.g., steroids.

- Current or prior treatment with CGY or History of hypersensitivity to CGY.

- Intellectual disability as defined in DSM V.