- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03794076
Cromoglicate Adjunctive Therapy for Outpatients With Schizophrenia (CATOS)
January 4, 2024 updated by: Vishwajit Nimgaonkar, MD PhD
Cromoglicte Adjunctive Therapy for Outpatients With Schizophrenia
This is a double blind adjunctive randomized controlled trial for schizophrenia using cromoglicate.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Estimated)
160
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Vishwajit L Nimgaonkar, M.D., Ph.D.
- Phone Number: (412) 246-6353
- Email: vishwajitNL@upmc.edu
Study Contact Backup
- Name: Maribeth A Wesesky, BPS
- Phone Number: (412) 310-3108
- Email: weseskyma@upmc.edu
Study Locations
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, United States, 15213
- Recruiting
- University of Pittsburgh
-
Sub-Investigator:
- Satish Iyengar, Ph.D.
-
Sub-Investigator:
- Konasale Prasad, M.D.
-
Sub-Investigator:
- Maribeth A Wesesky, BPS
-
Contact:
- Maribeth A Wesesky, BPS
- Phone Number: 412-310-3108
- Email: weseskyma@upmc.edu
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Cromoglycate
Cromoglycate nasal spray
|
Cromoglycate will be administered intranasally (nasal spray) (1 spray each nostril 4 times a day, 5.2 mg/spray
Other Names:
Normal saline nasal spray will be administered intranasally (nasal spray) (1 spray each nostril 4 times a day, 5.2 mg/spray)
Other Names:
|
Placebo Comparator: Placebo
Saline nasal spray
|
Cromoglycate will be administered intranasally (nasal spray) (1 spray each nostril 4 times a day, 5.2 mg/spray
Other Names:
Normal saline nasal spray will be administered intranasally (nasal spray) (1 spray each nostril 4 times a day, 5.2 mg/spray)
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Improvement in positive symptoms
Time Frame: 12 weeks
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Total Symptoms
Time Frame: 12 weeks
|
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
|
Negative Symptoms
Time Frame: 12 weeks
|
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
|
Cognition
Time Frame: 12 weeks
|
As measured by the Penn Computerized Neurocognitive Battery (CNB)
|
12 weeks
|
Sheehan's disability scale (SDS)
Time Frame: 12 Weeks
|
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
|
Global Assessment of Function (GAF)
Time Frame: 12 weeks
|
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
|
Quality of Life Scale (QOL)
Time Frame: 12 weeks
|
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
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Global Assessment of Function (GAF)
Time Frame: 12 weeks
|
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
|
Quality of Life Scale (QOL)
Time Frame: 12 weeks
|
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
|
Total Positive and Negative Syndrome Scale (PANSS)
Time Frame: 12 weeks
|
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
|
Penn Computerized Neurocognitive Battery (CNB)
Time Frame: 12 weeks
|
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
|
Sheehan's disability scale (SDS)
Time Frame: 12 weeks
|
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
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Vishwajit L. Nimgaonkar, M.D., Ph.D., University of Pittsburgh
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 1, 2019
Primary Completion (Estimated)
August 1, 2024
Study Completion (Estimated)
August 1, 2024
Study Registration Dates
First Submitted
January 2, 2019
First Submitted That Met QC Criteria
January 3, 2019
First Posted (Actual)
January 4, 2019
Study Record Updates
Last Update Posted (Actual)
January 5, 2024
Last Update Submitted That Met QC Criteria
January 4, 2024
Last Verified
January 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Schizophrenia Spectrum and Other Psychotic Disorders
- Schizophrenia
- Psychotic Disorders
- Mood Disorders
- Physiological Effects of Drugs
- Anti-Inflammatory Agents
- Immunologic Factors
- Anti-Asthmatic Agents
- Respiratory System Agents
- Anti-Allergic Agents
- Mast Cell Stabilizers
- Cromolyn Sodium
Other Study ID Numbers
- PRO18060112
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
IPD Plan Description
No individual subject data will be shared.
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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