Aspirin in Young Psychotic Patients

May 19, 2024 updated by: Dragana Pavićević, Clinic for Psychiatric Disorders, Dr Laza Lazarevic

Aspirin as Adjuvant Therapy in Young Psychotic Patients

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 (10th revision of the International Statistical Classification of Diseases and Related Health Problems) 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 experimental group (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.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Serbia
      • Belgrade, Serbia, 11000
        • Clinic for psychiatric disorders Dr Laza Lazarevic

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 28 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 18 to 28 years of life
  • diagnostic categories from F 20 to F 29, according to ICD 10 (International Classification of Diseases Version 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 (Chronic obstructive pulmonary disease), 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

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: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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 Names:
  • Acetylsalicylic acid
Drug: Pantoprazole
Pantoprazole 40 mg/pd in two doses, for gastric protection
Other Names:
  • Controloc
  • Protonix
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 Names:
  • sugar pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neurological Soft Signs
Time Frame: Comparison of total scores on Heidelberg scale between groups (aspirin and placebo group) after 6 weeks of treatment.

Neurological soft signs were assessed with the Heidelberg Scale which consists of five subscales (motor coordination, integrative functions, complex motor tasks, orientation, hard signs) comprising 16 items (gait, tandem walking, right/left orientation, arm holding test, finger to nose test, Ozeretzki's test, diadochokinesis, pronation-supination, finger to thumb opposition, mirror movements, two point discrimination, graphaesthesia, face- hand test, stereognosis, fist- edge- palm test, speech and articulation).

Ratings are given on a 0-3 point scale (no/slight/moderate/marked abnormality, respectively) for all items except for tandem walking (0-1 point scale; 0: no/slight, 1: moderate/marked abnormality). Scale ranges: minimum- 0 (better outcome), maximum 46 points (worse outcome).
Comparison of total scores on Heidelberg scale between groups (aspirin and placebo group) after 6 weeks of treatment.
Psychopathology Symptoms Assessed by PANSS
Time Frame: Comparison of total scores on PANSS (aspirin and placebo group) after 6 weeks of treatment.

The Positive and Negative Syndrome Scale (PANSS) is 30 item scale used to evaluate the presence, absence and severity of Positive, Negative and General Psychopathology symptoms of schizophrenia. Ratings are given on a 1-7 point scale (1- absent, 2- minimal, 3- mild, 4- moderate, 5- moderate severe, 6- severe, 7- extreme). Patient can not score lower than 30 for the total PANSS score. Maximum score is 210.

Higher scores mean a worse outcome.
Comparison of total scores on PANSS (aspirin and placebo group) after 6 weeks of treatment.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cognitive Assessment by MoCA Scale
Time Frame: Comparison of total scores on MoCA scale (aspirin and placebo group) after 6 weeks of treatment.
The Montreal Cognitive Assessment (MoCA) is a test used to detect cognitive decline. The MoCA test examines seven domains (executive/visuospatial function, naming, attention, language, abstraction, recall, and orientation) of cognitive function with a total of 11 questions with a maximum score of 30. A score of 26 or over is considered to be normal. A score of less than 26 indicates cognitive impairment (worse outcome). Minimal score is 0.
Comparison of total scores on MoCA scale (aspirin and placebo group) after 6 weeks of treatment.
Marker of Inflammation: C-reactive Protein (CRP)
Time Frame: Comparison of CRP levels between groups (aspirin and placebo group) after six weeks of treatment.
A C-reactive protein (CRP) test measures the level of C-reactive protein - a protein made by liver and releases in bloodstream in response to inflammation. Levels below 5 milligrams per liter (mg/L) are usually considered normal or free from infections.
Comparison of CRP levels between groups (aspirin and placebo group) after six weeks of treatment.
Marker of Inflammation- White Blood Cells (WBC)
Time Frame: Comparison of WBC levels (aspirin and placebo group) after 6 weeks of treatment.
A white blood cell (WBC) count is a test that measures the number of white blood cells in blood. A white blood cell count can detect infections within body. The normal white blood cell count ranges between 4,000 and 11,000 cells per microliter.
Comparison of WBC levels (aspirin and placebo group) after 6 weeks of treatment.
Cytokine Profile- Th1- Interferon Gamma (IFN-γ)
Time Frame: Comparison of IFN Gamma levels (aspirin and placebo group) after 6 weeks of treatment
Change of Interferon Gamma (IFN-γ) immune response
Comparison of IFN Gamma levels (aspirin and placebo group) after 6 weeks of treatment
Cytokine Profile- Th2-Interleukin 4 (IL4)
Time Frame: Comparison of IL 4 levels (aspirin and placebo group) after 6 weeks of treatment
Change of IL4 immune response
Comparison of IL 4 levels (aspirin and placebo group) after 6 weeks of treatment
Cytokine Profile- Type 17- Interleukin 17 (IL17)
Time Frame: Comparison of IL 17 levels (aspirin and placebo group) after 6 weeks of treatment
Change of IL17 immune response
Comparison of IL 17 levels (aspirin and placebo group) after 6 weeks of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Clinic for Psychiatric Disorders, Dr Laza Lazarevic

Collaborators

Stanley Medical Research Institute

Investigators

  • Principal Investigator: Dragana Pavićević, psychiatrist, Clinic for psychiatric disorder Dr Laza Lazarević

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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)

July 20, 2017

Primary Completion (Actual)

December 31, 2019

Study Completion (Actual)

December 31, 2019

Study Registration Dates

First Submitted

February 8, 2016

First Submitted That Met QC Criteria

February 14, 2016

First Posted (Estimated)

February 19, 2016

Study Record Updates

Last Update Posted (Actual)

September 23, 2024

Last Update Submitted That Met QC Criteria

May 19, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • #15T-006

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data that underline the results of study:

  • scores of PANSS (cumulative positive, negative and general scores)
  • MoCA scale cumulative scores
  • Heidelberg scale cumulative scores
  • as well as levels of CRP, WBC and cytokines.

IPD Sharing Time Frame

Starting in January 2024. for 24 months.

IPD Sharing Access Criteria

Investigators who proposed use of data has been approved by an independent review committee for meta analysis.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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