Aspirin in Young Psychotic Patients

NCT02685748 | Completed Phase 2 Results DMC

• 1 other identifier: #15T-006
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Psychosis; Acute Psychosis; Schizophrenia

Outcome Measures

Primary Outcomes (2)

• 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).

  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.

  Comparison of total scores on PANSS (aspirin and placebo group) after 6 weeks of treatment.

Secondary Outcomes (6)

• Cognitive Assessment by MoCA Scale

  Comparison of total scores on MoCA scale (aspirin and placebo group) after 6 weeks of treatment.

• Marker of Inflammation: C-reactive Protein (CRP)

  Comparison of CRP levels between groups (aspirin and placebo group) after six weeks of treatment.

• Marker of Inflammation- White Blood Cells (WBC)

  Comparison of WBC levels (aspirin and placebo group) after 6 weeks of treatment.

• Cytokine Profile- Th1- Interferon Gamma (IFN-γ)

  Comparison of IFN Gamma levels (aspirin and placebo group) after 6 weeks of treatment

• Cytokine Profile- Th2-Interleukin 4 (IL4)

  Comparison of IL 4 levels (aspirin and placebo group) after 6 weeks of treatment

Study Arms (2)

Aspirin & pantoprazole

EXPERIMENTAL

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

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.

Drug: Placebo

Interventions

Aspirin DRUG

1000 mg pd in two doses

Also known as: Acetylsalicylic acid

Aspirin & pantoprazole

Placebo DRUG

two pills twice a day (instead of aspirin and pantoprazole)

Also known as: sugar pill

Placebo

Pantoprazole DRUG

Pantoprazole 40 mg/pd in two doses, for gastric protection

Also known as: Protonix, Controloc

Aspirin & pantoprazole

Eligibility Criteria

• Age: 18 Years - 28 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Clinic for Psychiatric Disorders, Dr Laza Lazarevic: lead
• Stanley Medical Research Institute: collaborator

Study Sites (1)

Clinic for psychiatric disorders Dr Laza Lazarevic

Belgrade, 11000, Serbia

Location

Related Publications (15)

• 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.

  PMID: 22023091 BACKGROUND

• Bombin 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.

  PMID: 15958818 BACKGROUND

• Heinrichs 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.

  PMID: 3276226 BACKGROUND

• Hirjak 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.

  PMID: 25147527 BACKGROUND

• Schroder 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.

  PMID: 1786233 BACKGROUND

• Bachmann 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.

  PMID: 16330599 BACKGROUND

• Maynard 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.

  PMID: 11596847 BACKGROUND

• Feigenson 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.

  PMID: 24247023 BACKGROUND

• Mousa 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.

  PMID: 23880850 BACKGROUND

• Monji 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.

  PMID: 19579286 BACKGROUND

• Avgustin 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.

  PMID: 15849849 BACKGROUND

• Borovcanin 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.

  PMID: 22974591 BACKGROUND

• Borovcanin 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.

  PMID: 23602340 BACKGROUND

• Laan 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.

  PMID: 20492850 BACKGROUND

• Sommer 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.

  PMID: 24106335 BACKGROUND

Related Links

• Stoyanova M, Hranov L. Soft neurological signs in patients with bipolar disorder. European Psychiatry, 2014: 29 (1) 1
• Schröder J, Heuser M. Neurological Soft Signs in First -Episode Schizophrenia. Directions in Psychiatry 2008, Vol. 28 (19): 243-57.
• Howard, J. (2013) The cytokine hypothesis: A neurodevelopmental explanation for the emergence of schizophrenia later in life. Advances in Bioscience and Biotechnology, 4, 81-88

MeSH Terms

Conditions

Psychotic Disorders; Schizophrenia

Interventions

Aspirin; Sugars; Pantoprazole

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Carbohydrates; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Acute phase of disorder, small number of patients

Results Point of Contact

• Title: Pavicevic Dragana
• Organization: CPD Dr Laza Lazarevic, Belgrade, Serbia

gagapavicevic@yahoo.com

0652207970

Study Officials

• Dragana Pavićević, psychiatrist

  Clinic for psychiatric disorder Dr Laza Lazarević

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr Dragana Pavicevic

Study Record Dates

• First Submitted: February 8, 2016
• First Posted: February 19, 2016
• Study Start: July 20, 2017
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: September 23, 2024
• Results First Posted: September 23, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Starting in January 2024. for 24 months.
• Access Criteria: Investigators who proposed use of data has been approved by an independent review committee for meta analysis.

Locations

SE (1)