PsychosisPhase 2/3NCT02685748
Aspirin in Young Psychotic Patients
A Phase 2/3 study testing Aspirin and Pantoprazole in people with Psychosis and Acute Psychosis, run by Clinic for Psychiatric Disorders, Dr Laza Lazarevic at 1 site in Serbia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 28 years
- Conditions the study is for
- Psychosis, Acute Psychosis, Schizophrenia
- What is being tested?
- Aspirin and Pantoprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteSerbia
- Study dates
- 20 Jul 2017to 31 Dec 2019
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 28 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Serbia1 site
Clinic for psychiatric disorders Dr Laza Lazarevic
Belgrade, 11000
About this study
Official title: 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.
Read the 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.
- Conditions
- Psychosis, Acute Psychosis, Schizophrenia
- Being tested
- Aspirin, Placebo, Pantoprazole
- Medical subject headings
- Psychotic Disorders, Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AspirinDrug
Also called Acetylsalicylic acid
1000 mg pd in two doses
PlaceboDrug
Also called sugar pill
two pills twice a day (instead of aspirin and pantoprazole)
PantoprazoleDrug
Also called Protonix, Controloc
Pantoprazole 40 mg/pd in two doses, for gastric protection
| Study group | Role | What they receive |
|---|---|---|
| Aspirin & pantoprazole | Experimental | Aspirin 1000 mg/pd per os in two doses
Pantoprazole 40 mg/pd per os in two doses for gastric protection Receives: Drug: Aspirin; Drug: Pantoprazole |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neurological Soft Signs
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).
Measured: Comparison of total scores on Heidelberg scale between groups (aspirin and placebo group) after 6 weeks of treatment.
Psychopathology Symptoms Assessed by PANSS
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.
Measured: Comparison of total scores on PANSS (aspirin and placebo group) after 6 weeks of treatment.
Secondary outcomes (6)
Cognitive Assessment by MoCA Scale
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.
Measured: Comparison of total scores on MoCA scale (aspirin and placebo group) after 6 weeks of treatment.
Marker of Inflammation: C-reactive Protein (CRP)
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.
Measured: Comparison of CRP levels between groups (aspirin and placebo group) after six weeks of treatment.
Marker of Inflammation- White Blood Cells (WBC)
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.
Measured: Comparison of WBC levels (aspirin and placebo group) after 6 weeks of treatment.
Cytokine Profile- Th1- Interferon Gamma (IFN-γ)
Change of Interferon Gamma (IFN-γ) immune response
Measured: Comparison of IFN Gamma levels (aspirin and placebo group) after 6 weeks of treatment
Cytokine Profile- Th2-Interleukin 4 (IL4)
Change of IL4 immune response
Measured: Comparison of IL 4 levels (aspirin and placebo group) after 6 weeks of treatment
Cytokine Profile- Type 17- Interleukin 17 (IL17)
Change of IL17 immune response
Measured: Comparison of IL 17 levels (aspirin and placebo group) after 6 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2016 (estimated)
- Study start20 Jul 2017
- Primary completion31 Dec 2019
- Study completion31 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for PsychosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Clinic for Psychiatric Disorders, Dr Laza Lazarevic
- Sponsor type
- University, hospital or other
- Collaborators
- Stanley Medical Research Institute
- Responsible party
- Principal investigator, Dragana Pavićević, Clinic for Psychiatric Disorders, Dr Laza Lazarevic
- Investigators
- Dragana Pavićević, psychiatrist, Principal investigator, Clinic for psychiatric disorder Dr Laza Lazarević
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02685748
- Sponsor's protocol ID
- #15T-006
- Status last verified
- May 2024
- First submitted
- 8 Feb 2016
- Last updated
- 23 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Mayoral M, Bombin I, Castro-Fornieles J, Gonzalez-Pinto A, Otero S, Parellada M, Moreno D, Baeza I, Graell M, Rapado M, Arango C. Longitudinal study of neurological soft signs in first-episode early-onset psychosis. J Child Psychol Psychiatry. 2012 Mar;53(3):323-31. doi: 10.1111/j.1469-7610.2011.02475.x. Epub 2011 Oct 25.
PubMed 22023091Bombin I, Arango C, Buchanan RW. Significance and meaning of neurological signs in schizophrenia: two decades later. Schizophr Bull. 2005 Oct;31(4):962-77. doi: 10.1093/schbul/sbi028. Epub 2005 Jun 15.
PubMed 15958818Heinrichs DW, Buchanan RW. Significance and meaning of neurological signs in schizophrenia. Am J Psychiatry. 1988 Jan;145(1):11-8. doi: 10.1176/ajp.145.1.11.
PubMed 3276226Hirjak D, Wolf RC, Koch SC, Mehl L, Kelbel JK, Kubera KM, Traeger T, Fuchs T, Thomann PA. Neurological abnormalities in recent-onset schizophrenia and asperger-syndrome. Front Psychiatry. 2014 Aug 6;5:91. doi: 10.3389/fpsyt.2014.00091. eCollection 2014.
PubMed 25147527Schroder J, Niethammer R, Geider FJ, Reitz C, Binkert M, Jauss M, Sauer H. Neurological soft signs in schizophrenia. Schizophr Res. 1991 Dec;6(1):25-30. doi: 10.1016/0920-9964(91)90017-l.
PubMed 1786233Bachmann S, Bottmer C, Schroder J. Neurological soft signs in first-episode schizophrenia: a follow-up study. Am J Psychiatry. 2005 Dec;162(12):2337-43. doi: 10.1176/appi.ajp.162.12.2337.
PubMed 16330599Maynard TM, Sikich L, Lieberman JA, LaMantia AS. Neural development, cell-cell signaling, and the "two-hit" hypothesis of schizophrenia. Schizophr Bull. 2001;27(3):457-76. doi: 10.1093/oxfordjournals.schbul.a006887.
PubMed 11596847Feigenson KA, Kusnecov AW, Silverstein SM. Inflammation and the two-hit hypothesis of schizophrenia. Neurosci Biobehav Rev. 2014 Jan;38:72-93. doi: 10.1016/j.neubiorev.2013.11.006. Epub 2013 Nov 15.
PubMed 24247023Mousa A, Bakhiet M. Role of cytokine signaling during nervous system development. Int J Mol Sci. 2013 Jul 4;14(7):13931-57. doi: 10.3390/ijms140713931.
PubMed 23880850Monji A, Kato T, Kanba S. Cytokines and schizophrenia: Microglia hypothesis of schizophrenia. Psychiatry Clin Neurosci. 2009 Jun;63(3):257-65. doi: 10.1111/j.1440-1819.2009.01945.x.
PubMed 19579286Avgustin B, Wraber B, Tavcar R. Increased Th1 and Th2 immune reactivity with relative Th2 dominance in patients with acute exacerbation of schizophrenia. Croat Med J. 2005 Apr;46(2):268-74.
PubMed 15849849Borovcanin M, Jovanovic I, Radosavljevic G, Djukic Dejanovic S, Bankovic D, Arsenijevic N, Lukic ML. Elevated serum level of type-2 cytokine and low IL-17 in first episode psychosis and schizophrenia in relapse. J Psychiatr Res. 2012 Nov;46(11):1421-6. doi: 10.1016/j.jpsychires.2012.08.016. Epub 2012 Sep 10.
PubMed 22974591Borovcanin M, Jovanovic I, Radosavljevic G, Djukic Dejanovic S, Stefanovic V, Arsenijevic N, Lukic ML. Antipsychotics can modulate the cytokine profile in schizophrenia: attenuation of the type-2 inflammatory response. Schizophr Res. 2013 Jun;147(1):103-109. doi: 10.1016/j.schres.2013.03.027. Epub 2013 Apr 16.
PubMed 23602340Laan W, Grobbee DE, Selten JP, Heijnen CJ, Kahn RS, Burger H. Adjuvant aspirin therapy reduces symptoms of schizophrenia spectrum disorders: results from a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2010 May;71(5):520-7. doi: 10.4088/JCP.09m05117yel.
PubMed 20492850Sommer IE, van Westrhenen R, Begemann MJ, de Witte LD, Leucht S, Kahn RS. Efficacy of anti-inflammatory agents to improve symptoms in patients with schizophrenia: an update. Schizophr Bull. 2014 Jan;40(1):181-91. doi: 10.1093/schbul/sbt139. Epub 2013 Oct 8.
PubMed 24106335
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Aspirin as Adjuvant Therapy in Young Psychotic Patients
- ClinicalTrials.gov ID
- NCT02685748
- Acronym / sponsor ID
- #15T-006
- Conditions
- Psychosis, Acute Psychosis, Schizophrenia
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Clinic for Psychiatric Disorders, Dr Laza LazarevicUniversity, hospital or other
- Collaborators
- Stanley Medical Research Institute
- Study start
- 20 Jul 2017 (actual)
- Primary completion
- 31 Dec 2019 (actual)
- Study completion
- 31 Dec 2019 (actual)
- First posted
- 19 Feb 2016 (estimated)
- Results
- Posted 23 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 (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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aspirin & pantoprazole | Experimental | Drug: Aspirin, Drug: PantoprazoleAspirin 1000 mg/pd per os in two doses Pantoprazole 40 mg/pd per os in two doses for gastric protection |
| Placebo | Placebo comparator | Drug: PlaceboTwo pills in the morning and two in the evening All pills (aspirin, pantoprazole an placebo) will be the same looking- in the same capsules. |
Who may qualify
- Ages
- 18 to 28 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AspirinAlso: Acetylsalicylic acid1000 mg pd in two doses | Drug | Aspirin & pantoprazole |
| PlaceboAlso: sugar pilltwo pills twice a day (instead of aspirin and pantoprazole) | Drug | Placebo |
| PantoprazoleAlso: Protonix, ControlocPantoprazole 40 mg/pd in two doses, for gastric protection | Drug | Aspirin & pantoprazole |
Primary outcome
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).
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.
6 secondary outcomes
Cognitive Assessment by MoCA Scale
Time frame: 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.
Marker of Inflammation- White Blood Cells (WBC)
Time frame: 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
Cytokine Profile- Th2-Interleukin 4 (IL4)
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22023091Mayoral M, Bombin I, Castro-Fornieles J, Gonzalez-Pinto A, Otero S, Parellada M, Moreno D, Baeza I, Graell M, Rapado M, Arango C. Longitudinal study of neurological soft signs in first-episode early-onset psychosis. J Child Psychol Psychiatry. 2012 Mar;53(3):323-31. doi: 10.1111/j.1469-7610.2011.02475.x. Epub 2011 Oct 25.
- Background: PubMed 15958818Bombin I, Arango C, Buchanan RW. Significance and meaning of neurological signs in schizophrenia: two decades later. Schizophr Bull. 2005 Oct;31(4):962-77. doi: 10.1093/schbul/sbi028. Epub 2005 Jun 15.
- Background: PubMed 3276226Heinrichs DW, Buchanan RW. Significance and meaning of neurological signs in schizophrenia. Am J Psychiatry. 1988 Jan;145(1):11-8. doi: 10.1176/ajp.145.1.11.
- Background: PubMed 25147527Hirjak D, Wolf RC, Koch SC, Mehl L, Kelbel JK, Kubera KM, Traeger T, Fuchs T, Thomann PA. Neurological abnormalities in recent-onset schizophrenia and asperger-syndrome. Front Psychiatry. 2014 Aug 6;5:91. doi: 10.3389/fpsyt.2014.00091. eCollection 2014.
- Background: PubMed 1786233Schroder J, Niethammer R, Geider FJ, Reitz C, Binkert M, Jauss M, Sauer H. Neurological soft signs in schizophrenia. Schizophr Res. 1991 Dec;6(1):25-30. doi: 10.1016/0920-9964(91)90017-l.
- Background: PubMed 16330599Bachmann S, Bottmer C, Schroder J. Neurological soft signs in first-episode schizophrenia: a follow-up study. Am J Psychiatry. 2005 Dec;162(12):2337-43. doi: 10.1176/appi.ajp.162.12.2337.
- Background: PubMed 11596847Maynard TM, Sikich L, Lieberman JA, LaMantia AS. Neural development, cell-cell signaling, and the "two-hit" hypothesis of schizophrenia. Schizophr Bull. 2001;27(3):457-76. doi: 10.1093/oxfordjournals.schbul.a006887.
- Background: PubMed 24247023Feigenson KA, Kusnecov AW, Silverstein SM. Inflammation and the two-hit hypothesis of schizophrenia. Neurosci Biobehav Rev. 2014 Jan;38:72-93. doi: 10.1016/j.neubiorev.2013.11.006. Epub 2013 Nov 15.
- Background: PubMed 23880850Mousa A, Bakhiet M. Role of cytokine signaling during nervous system development. Int J Mol Sci. 2013 Jul 4;14(7):13931-57. doi: 10.3390/ijms140713931.
- Background: PubMed 19579286Monji A, Kato T, Kanba S. Cytokines and schizophrenia: Microglia hypothesis of schizophrenia. Psychiatry Clin Neurosci. 2009 Jun;63(3):257-65. doi: 10.1111/j.1440-1819.2009.01945.x.
- Background: PubMed 15849849Avgustin B, Wraber B, Tavcar R. Increased Th1 and Th2 immune reactivity with relative Th2 dominance in patients with acute exacerbation of schizophrenia. Croat Med J. 2005 Apr;46(2):268-74.
- Background: PubMed 22974591Borovcanin M, Jovanovic I, Radosavljevic G, Djukic Dejanovic S, Bankovic D, Arsenijevic N, Lukic ML. Elevated serum level of type-2 cytokine and low IL-17 in first episode psychosis and schizophrenia in relapse. J Psychiatr Res. 2012 Nov;46(11):1421-6. doi: 10.1016/j.jpsychires.2012.08.016. Epub 2012 Sep 10.
- Stoyanova M, Hranov L. Soft neurological signs in patients with bipolar disorder. European Psychiatry, 2014: 29 (1) 1Link provided by the sponsor.
- Schröder J, Heuser M. Neurological Soft Signs in First -Episode Schizophrenia. Directions in Psychiatry 2008, Vol. 28 (19): 243-57.Link provided by the sponsor.
- Howard, J. (2013) The cytokine hypothesis: A neurodevelopmental explanation for the emergence of schizophrenia later in life. Advances in Bioscience and Biotechnology, 4, 81-88Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dragana Pavićević, psychiatrist principal investigator
Clinic for psychiatric disorder Dr Laza Lazarević
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Aspirin and Pantoprazole in people with Psychosis and Acute Psychosis, run by Clinic for Psychiatric Disorders, Dr Laza Lazarevic at 1 site in Serbia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Serbia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neurological Soft Signs (time frame: Comparison of total scores on Heidelberg scale between groups (aspirin and placebo group) after 6 weeks of treatment.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02685748, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2024.