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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

Tracking Information
First Submitted Date  ICMJE February 8, 2016
First Posted Date  ICMJE February 19, 2016
Last Update Posted Date January 15, 2019
Actual Study Start Date  ICMJE July 20, 2017
Estimated Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 14, 2016)
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)
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02685748 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 14, 2016)
  • Changes of psychopathology [ Time Frame: Change after six weeks of treatment from baseline ]
    PANSS total, positive, negative and general psychopathology scores
  • Change of Cognition [ Time Frame: Change after six weeks of treatment from baseline ]
    MoCA scale scores
  • 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
  • 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
  • Change of Cytokine profile- Th1 [ Time Frame: Change after six weeks of treatment from baseline ]
    Change of Th1 immune response
  • Change of Cytokine profile- Th2 [ Time Frame: Change after six weeks of treatment from baseline ]
    Change of Th2 immune response
  • Change of Cytokine profile- type 17 [ Time Frame: Change after six weeks of treatment from baseline ]
    Change of Type-17 immune response
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Aspirin in Young Psychotic Patients
Official Title  ICMJE Aspirin as Adjuvant Therapy in Young Psychotic Patients
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Psychosis
  • Acute Psychosis
  • Schizophrenia
Intervention  ICMJE
  • Drug: Aspirin
    1000 mg pd in two doses
    Other Name: Acetylsalicylic acid
  • Drug: Placebo
    two pills twice a day (instead of aspirin and pantoprazole)
    Other Name: sugar pill
  • Drug: Pantoprazole
    Pantoprazole 40 mg/pd in two doses, for gastric protection
    Other Names:
    • Protonix
    • Controloc
Study Arms  ICMJE
  • 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
    • Drug: Pantoprazole
  • 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.

    Intervention: Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 14, 2016)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2020
Estimated Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 28 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Dragana Pavićević, psychiatrist 65.2207970 ext +381
Contact: Đorđe Ćurčić, psychiatrist
Listed Location Countries  ICMJE Serbia
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02685748
Other Study ID Numbers  ICMJE #15T-006
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Dragana Pavićević, Clinic for Psychiatric Disorders, Dr Laza Lazarevic
Study Sponsor  ICMJE Clinic for Psychiatric Disorders, Dr Laza Lazarevic
Collaborators  ICMJE Stanley Medical Research Institute
Investigators  ICMJE
Principal Investigator: Dragana Pavićević, psychiatrist Emergency Department & Intensive Care Unit, Clinic for psychiatric disorder Dr Laza Lazarević
PRS Account Clinic for Psychiatric Disorders, Dr Laza Lazarevic
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP