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Aspirin in Young Psychotic Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02685748
Recruitment Status : Recruiting
First Posted : February 19, 2016
Last Update Posted : January 15, 2019
Stanley Medical Research Institute
Information provided by (Responsible Party):
Dragana Pavićević, Clinic for Psychiatric Disorders, Dr Laza Lazarevic

Brief Summary:
In this double blind randomized clinical trial the investigators are going to exam influence of adjuvant Aspirin therapy on soft neurological signs (Heidelberg scale), positive and negative symptoms (PANSS), cytokine profile and inflammatory factors, as well as on cognition (MoCA) in young psychotic patients.

Condition or disease Intervention/treatment Phase
Psychosis Acute Psychosis Schizophrenia Drug: Aspirin Drug: Placebo Drug: Pantoprazole Phase 2 Phase 3

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Detailed Description:

Schizophrenia as psychiatric paradigm is one of the most mysterious mental illness, for decades remains a challenge to many clinicians and researchers with its complex, fundamental mechanisms.

Soft neurological signs (SNS) are described as non-localized neurological abnormalities that cannot be associated with damage of a specific brain region. It is believed that they are not part of a well-defined neurological syndrome. They include neurological abnormalities with deficits in sensory integration, motor coordination and sequencing of complex motor acts. They have a higher prevalence in schizophrenic patients compared to healthy population. Moreover, SNS have been consistently demonstrated in neuroleptic naive patients in the first episode of illness. There is also an increased prevalence in non- schizophrenic relatives of patients with schizophrenia. It is considered that they are not potentiated by antipsychotics. For all these reasons it is believed that they are the inherent quality of schizophrenia - "trait" marker, or endophenotypes.

According to the so-called "Two hit" hypothesis in the development of schizophrenia, there are two periods of increased vulnerability. The first one is in a fetal age when it comes to the interaction of genetic and environmental factors such as infection and inflammatory processes who may also serve this function. The second period of vulnerability is a period of adolescence, or early adult age when the influence of environmental factors leads to clinical manifestations of the disease. It is thought that cytokines have key role in the first strike.

Cytokines are mediators of communication between the neural elements in all aspects of the development of the nervous system. Until now, numerous studies indicated modification of specific cytokines in psychotic disorders and their possible role in the proposed concept of "microglial hypothesis" of schizophrenia. Hypothesis of activation Th1 and Th2 immune response, with a predominance of Th2 immune response is proposed in schizophrenia. Type-17 cytokines are important in mediating tissue damage in autoimmune diseases. Regulatory cytokines suppress immune responses and maintain self-tolerance.

Consequently, the question is whether the combination of antipsychotic drugs with anti-inflammatory drugs is more useful than independent antipsychotic therapy? Laan and colleagues in 2010. carried out a randomized, double- blind, placebo - controlled study to determine if the adjuvant aspirin therapy could be useful for patients who are already taking antipsychotics. They concluded that the therapy antipsychotic + aspirin was significantly superior to placebo + antipsychotic therapy. PANSS score was significantly lower in the aspirin group.

The aim of the study would be to determine the effects of adjuvant aspirin therapy on soft neurological signs, PANSS and the cytokine profile. The investigators expect the reduction of PANSS scores in both groups of patients (aspirin group and placebo group). If there is no significant changes of SNS between groups, the results would support SNS as trait characteristics of schizophrenia. In the case of significant changes of cytokine profile/ratios in experimental group, the results would go in favour of the cytokine hypothesis.

The research would be done on hospitalized patients at the Clinic for Psychiatric Disorders "Dr Laza Lazarevic" in Belgrade. Part of the study (immunology) will be done on Medical Faculty University of Kragujevac. The study would be a randomized, double-blind, placebo controlled in two parallel groups of 50 to 60 patients who are neuroleptic naive or previously minimally medicated (in the past 6 months without any antipsychotic treatment) with the duration of the illness up to seven years. The study would involve the patients of both sexes, aged 18 to 28 years, according to ICD 10 criteria to satisfy diagnosis F 20 to F 29. Each patient who enters the hospital and meets the inclusion criteria would be taken into consideration. If patient satisfies exclusion criteria and sign consent, then s/he would be randomized into two groups: Experimental group (antipsychotic + aspirin) and Control group (antipsychotic + placebo). Patients in EG would receive 1,000 mg of aspirin pro die and pantoprazole 40 mg pro die in two doses for gastric protection.

Only one researcher would know in which group patient belongs (would be responsible only for randomization, would not be rater or treating psychiatrist). The same researcher would give boxes with medications marked with the patient's name. In fact, all medications (aspirin, pantoprazole, and placebo) would be packaged in the same looking capsules.

The protocol would consist of three planned visits for patients in both groups. On the first visit blood samples would be taken for the implementation of immunological tests as well as for laboratory inflammatory factors; patients would be subjected to clinical psychiatric and physical examination, BMI measurement; PANSS scale will be done. After calming the signs of acute psychosis, on 3rd day, patients would be examined with Heidelberg and MoCA scale; patients would start to take Aspirin or Placebo. At the end of 6th week from the second visit, on the third visit, blood samples would be taken again for analyzing cytokine profile and inflammatory factors. PANSS, Heidelberg and MoCA scales would be performed again.

The investigators would consider the following factors: patient sex, age of the patients, clinical characteristics, the role of heredity, type of therapy/ prescribed typical or atypical antipsychotic; side effects of treatment and type of treatment response. Serum concentrations of cytokines will be examined with commercial ELISA tests.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Aspirin as Adjuvant Therapy in Young Psychotic Patients
Actual Study Start Date : July 20, 2017
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Aspirin & pantoprazole

Aspirin 1000 mg/pd per os in two doses

Pantoprazole 40 mg/pd per os in two doses for gastric protection

Drug: Aspirin
1000 mg pd in two doses
Other Name: Acetylsalicylic acid

Drug: Pantoprazole
Pantoprazole 40 mg/pd in two doses, for gastric protection
Other Names:
  • Protonix
  • Controloc

Placebo Comparator: Placebo

Two pills in the morning and two in the evening

All pills (aspirin, pantoprazole an placebo) will be the same looking- in the same capsules.

Drug: Placebo
two pills twice a day (instead of aspirin and pantoprazole)
Other Name: sugar pill

Primary Outcome Measures :
  1. Changes of Soft Neurological Signs [ Time Frame: Change from baseline after six weeks of treatment ]
    NSS will be assessed by Heidelberg NSS Scale, 16 items scale (motor coordination, integrative functions, complex motor tasks, orientation, hard signs)

Secondary Outcome Measures :
  1. Changes of psychopathology [ Time Frame: Change after six weeks of treatment from baseline ]
    PANSS total, positive, negative and general psychopathology scores

  2. Change of Cognition [ Time Frame: Change after six weeks of treatment from baseline ]
    MoCA scale scores

  3. Change of marker of inflammation- CRP [ Time Frame: Change after six weeks of treatment from baseline ]
    Change of C-reactive protein (CRP) after 6 week of treatment

  4. Change of marker of inflammation- WBC [ Time Frame: Change after six weeks of treatment from baseline ]
    Change of White Blood Cells count after 6 week of treatment

  5. Change of Cytokine profile- Th1 [ Time Frame: Change after six weeks of treatment from baseline ]
    Change of Th1 immune response

  6. Change of Cytokine profile- Th2 [ Time Frame: Change after six weeks of treatment from baseline ]
    Change of Th2 immune response

  7. Change of Cytokine profile- type 17 [ Time Frame: Change after six weeks of treatment from baseline ]
    Change of Type-17 immune response

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 28 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 18 to 28 years of life
  • diagnostic categories from F 20 to F 29, according to ICD 10 criteria
  • duration of illness ≤ 7 years

Exclusion Criteria:

  • Substance abuse
  • Primary cognitive impairment
  • Contraindications and special caution for acetylsalicylic acid and pantoprazole: hypersensitivity to aspirin and other NSAIDs or pantoprazole, ulcers, gastritis, pregnancy, haemophilia, bleeding disorders, gout, asthma, COPD, bronchospasm induced by NSAIDs, angioedema, urticaria, haemolytic anaemia, use of warfarin or methotrexate, diabetes, reduced function of liver and/or kidney, heart failure, surgical/dental intervention, interactions with certain psychotropic drugs

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02685748

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Contact: Dragana Pavićević, psychiatrist 65.2207970 ext +381
Contact: Đorđe Ćurčić, psychiatrist

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Clinic for psychiatric disorders Dr Laza Lazarevic Recruiting
Belgrade, Serbia, 11000
Contact: Nebojsa Zivkovic, MD         
Contact: Djordje Curcic, MD         
Principal Investigator: Dragana Pavicevic, MD         
Sub-Investigator: Slavica Djukic Dejanovic, Professor         
Sub-Investigator: Djordje Curcic, MD         
Sub-Investigator: Nebojsa Zivkovic, MD         
Sponsors and Collaborators
Clinic for Psychiatric Disorders, Dr Laza Lazarevic
Stanley Medical Research Institute
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Principal Investigator: Dragana Pavićević, psychiatrist Emergency Department & Intensive Care Unit, Clinic for psychiatric disorder Dr Laza Lazarević

Additional Information:

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Responsible Party: Dragana Pavićević, Dr Dragana Pavicevic, Clinic for Psychiatric Disorders, Dr Laza Lazarevic Identifier: NCT02685748     History of Changes
Other Study ID Numbers: #15T-006
First Posted: February 19, 2016    Key Record Dates
Last Update Posted: January 15, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Psychotic Disorders
Mental Disorders
Schizophrenia Spectrum and Other Psychotic Disorders
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Anti-Ulcer Agents
Gastrointestinal Agents
Proton Pump Inhibitors