Cromoglicate Adjunctive Therapy for Outpatients With Schizophrenia

NCT ID: NCT03794076

Last Updated: 2025-09-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-01
• Study Completion Date: 2026-06-30

Brief Summary

This is a double blind adjunctive randomized controlled trial for schizophrenia using cromoglicate.

Detailed Description

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.

Conditions

Schizophrenia; Schizo Affective Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Cromoglycate

Cromoglycate nasal spray

Group Type: ACTIVE_COMPARATOR

Cromoglycate

Intervention Type: DRUG

Cromoglycate will be administered intranasally (nasal spray) (1 spray each nostril 4 times a day, 5.2 mg/spray

Placebo

Intervention Type: DRUG

Normal saline nasal spray will be administered intranasally (nasal spray) (1 spray each nostril 4 times a day, 5.2 mg/spray)

Placebo

Saline nasal spray

Group Type: PLACEBO_COMPARATOR

Cromoglycate

Intervention Type: DRUG

Cromoglycate will be administered intranasally (nasal spray) (1 spray each nostril 4 times a day, 5.2 mg/spray

Placebo

Intervention Type: DRUG

Normal saline nasal spray will be administered intranasally (nasal spray) (1 spray each nostril 4 times a day, 5.2 mg/spray)

Interventions

Cromoglycate

Cromoglycate will be administered intranasally (nasal spray) (1 spray each nostril 4 times a day, 5.2 mg/spray

Intervention Type: DRUG

Placebo

Normal saline nasal spray will be administered intranasally (nasal spray) (1 spray each nostril 4 times a day, 5.2 mg/spray)

Intervention Type: DRUG

Other Intervention Names

NasalCrom; Saline Nasal Spray

Eligibility Criteria

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

• No illicit substance use in last 30 days/no dependence in 6 months with the exception of methadone treatment for opioid withdrawal.
• History or current medical /neurological illnesses that may lead to an unstable course with the exception of epilepsy which is well-controlled on an antiepileptic medication for at least 6 months.
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stanley Medical Research Institute

OTHER

Sponsor Role: collaborator

Vishwajit Nimgaonkar, MD PhD

OTHER

Sponsor Role: lead

Responsible Party

Vishwajit Nimgaonkar, MD PhD

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Vishwajit L. Nimgaonkar, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Vishwajit L Nimgaonkar, M.D., Ph.D.

Role: CONTACT

vishwajitNL@upmc.edu

(412) 246-6353

Maribeth A Wesesky, BPS

Role: CONTACT

weseskyma@upmc.edu

(412) 310-3108

Facility Contacts

Maribeth A Wesesky, BPS

Role: primary

weseskyma@upmc.edu

4123103108

Other Identifiers

STUDY19070355

Identifier Type: -

Identifier Source: org_study_id