Cromoglicate Adjunctive Therapy for Outpatients With Schizophrenia

Schizophrenia Clinical Trial

— CATOS  

Official title:

Cromoglicte Adjunctive Therapy for Outpatients With Schizophrenia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03794076
• Other study ID #: PRO18060112
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 1, 2019
• Est. completion date: August 2024

Study information

• Verified date: January 2024
• Source: University of Pittsburgh
• Contact: Vishwajit L Nimgaonkar, M.D., Ph.D.
• Phone: (412) 246-6353
• Email: vishwajitNL[@]upmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: August 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Mood Disorders
• Psychotic Disorders
• Schizo Affective Disorder
• Schizophrenia

Intervention

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

Locations

Country	Name	City	State
United States	University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Vishwajit Nimgaonkar, MD PhD	Stanley Medical Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Total Positive and Negative Syndrome Scale (PANSS)	Clinical Severity as determined by the Positive and Negative Syndrome Scale (PANSS) positive symptom subscale. The PANSS is a standardized, clinical interview that rates the presence and severity of positive and negative symptoms, as well as general psychopathology for people with schizophrenia within the past week. Symptom severity for each item is rated according to which anchoring points in the 7-point scale (1 = absent; 7 = extreme) best describe the presentation of the symptom. 30 Items, (minimum score = 7, maximum score = 210)	12 weeks
Other	Penn Computerized Neurocognitive Battery (CNB)	Developed in the Brain Behavior Lab at Penn, the CNB is a series of computerized tests that measure accuracy and speed of performance in major domains of cognition, including social-cognition. Battery measures the executive functions of abstraction and mental flexibility, attention, and working memory, episodic memory for words, faces and figures, intellectual functioning including verbal and nonverbal reasoning and spatial orientation, facial emotion processing and sensorimotor and motor speed. The participant completes this test on the computer with oversight by a research team member.	12 weeks
Other	Sheehan's disability scale (SDS)	The SDS is a brief, 5-item self-report tool that assesses functional impairment in work/school, social life, and family life. Total score 0-30 (0 unimpaired, 30 highly impaired)	12 weeks
Other	Global Assessment of Function (GAF)	The Global Assessment of Functioning, or GAF, scale is used to rate how serious a mental illness may be. It measures how much a person's symptoms affect his or her day-to-day life on a scale of 0 to 100.	12 weeks
Other	Quality of Life Scale (QOL)	Self-administered questionnaire designed for use in patients with chronic illnesses. 7-point Likert-type scale ranging from "delighted" (7) to "terrible" (1). Total scale score (possible range: 16 - 112)	12 weeks
Primary	Improvement in positive symptoms	Clinical Severity as determined by the Positive and Negative Syndrome Scale (PANSS) positive symptom subscale. The PANSS is a standardized, clinical interview that rates the presence and severity of positive and negative symptoms, as well as general psychopathology for people with schizophrenia within the past week. Symptom severity for each item is rated according to which anchoring points in the 7-point scale (1 = absent; 7 = extreme) best describe the presentation of the symptom. 7 Items, (minimum score = 7, maximum score = 49)	12 weeks
Secondary	Total Symptoms	Clinical Severity as determined by the Positive and Negative Syndrome Scale (PANSS) positive symptom subscale. The PANSS is a standardized, clinical interview that rates the presence and severity of positive and negative symptoms, as well as general psychopathology for people with schizophrenia within the past week. Symptom severity for each item is rated according to which anchoring points in the 7-point scale (1 = absent; 7 = extreme) best describe the presentation of the symptom. 30 Items, (minimum score = 7, maximum score = 210)	12 weeks
Secondary	Negative Symptoms	Clinical Severity as determined by the Positive and Negative Syndrome Scale (PANSS) positive symptom subscale. The PANSS is a standardized, clinical interview that rates the presence and severity of positive and negative symptoms, as well as general psychopathology for people with schizophrenia within the past week. Symptom severity for each item is rated according to which anchoring points in the 7-point scale (1 = absent; 7 = extreme) best describe the presentation of the symptom. 7 Items, (minimum score = 7, maximum score = 49)	12 weeks
Secondary	Cognition	As measured by the Penn Computerized Neurocognitive Battery (CNB)	12 weeks
Secondary	Sheehan's disability scale (SDS)	The SDS is a brief, 5-item self-report tool that assesses functional impairment in work/school, social life, and family life. Total score 0-30 (0 unimpaired, 30 highly impaired)	12 Weeks
Secondary	Global Assessment of Function (GAF)	The Global Assessment of Functioning, or GAF, scale is used to rate how serious a mental illness may be. It measures how much a person's symptoms affect his or her day-to-day life on a scale of 0 to 100.	12 weeks
Secondary	Quality of Life Scale (QOL)	Self-administered questionnaire designed for use in patients with chronic illnesses. 7-point Likert-type scale ranging from "delighted" (7) to "terrible" (1). Total scale score (possible range: 16 - 112)	12 weeks