Aspirin in Young Psychotic Patients
Condition: Psychosis; Acute Psychosis; Schizophrenia
MeSH terms: Schizophrenia; Psychotic Disorders; Mental Disorders
Study type: Interventional
Phase: Phase 2/Phase 3

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.

      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
      (+/- 3 days), 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.
    

Intervention name(s): Aspirin; Placebo; Pantoprazole
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 1000 mg pd in two doses; two pills twice a day (instead of aspirin and pantoprazole); Pantoprazole 40 mg/pd in two doses, for gastric protection
Other intervention name(s): Acetylsalicylic acid; sugar pill; Protonix; Controloc
Intervention MeSH terms: Aspirin; Pantoprazole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment