Prevalence of Clinical and Laboratory Markers of Hypofibrinolysis in Psychotic Patients

Insulin Resistance Clinical Trial

Official title:

Prevalence of Clinical and Laboratory Markers of Hypofibrinolysis in Psychotic Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01487291
• Other study ID #: UFRiodJaneiro
• Status: Completed
• Phase: N/A
• First received: December 5, 2011
• Last updated: December 15, 2014
• Start date: January 2013
• Est. completion date: May 2013

Study information

• Verified date: December 2014
• Source: Universidade Federal do Rio de Janeiro
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: Ethics Committee
• Study type: Observational

Clinical Trial Summary

At the Thrombophilia Clinic of the Hospital Federal dos Servidores do Estado do Rio de Janeiro there is a high prevalence of acute psychotic episodes, which allows the investigators to raise the suspicion that the thrombotic tendency or hypofibrinolysis play a role in the onset of the disease. It is striking that most of these patients, after some time on anticoagulants, no longer need to take psychiatric medication.

Description:

If the thrombotic tendency plays a significant role in the etiology of psychosis, one would expect to find ischemic brain injuries in neuroimaging studies, but it does not happen. Therefore, if there is a correlation between thrombotic tendency-hypofibrinolysis and psychosis it is likely to occur at the biochemical level, such as in neuronal transmission.

The investigators hypothesis is that mechanisms that inhibit tissue plasminogen activator (t-PA) and therefore promote hypofibrinolysis, are directly or indirectly involved in the genesis of psychosis, because t-PA participates in neuronal plasticity and low t-PA levels are related to dementia.

Hypofibrinolysis due to t-PA inhibition can be seen in:

• Insulin resistance, when the pancreas must produce large amounts of insulin and proinsulin by feedback. If pancreatic reserve is inadequate, the result is diabetes mellitus. If the response is adequate, proinsulin stimulates the production of PAI-1 (plasminogen activator inhibitor 1. PAI-1 inhibits the formation of plasmin, whose function is to dissolve fibrin which makes up the clot. Obesity, certain infections and inflammations potentiate insulin resistance.

• Antiphospholipid antibody syndrome.

• PAI-1 4G/5G or 4G/4G polymorphism.

Some hypofibrinolysis indicators are:

• severe dysmenorrhea, because strong uterine contractions are necessary to expel undissolved clots.

• PCOS because plasmin is required to activate some metalloproteinases involved in ovary remodelling.

• early pregnancy losses, as some metalloproteinases involved in placental angiogenesis are activated by plasmin,

• preeclampsia and eclampsia, as metalloproteinases that dissolve elastic fibers of the placental vessels, to create a low flow resistance, are activated by plasmin. Vascular endothelial growth factor (VEGF), a protein that restricts glomerular porosity, is also activated by plasmin,

• sudden death and heart attack before age 50 in first degree relatives.

On physical exam, acanthosis, high body mass index, and in women, hirsutism and acne are indirect indicators of insulin resistance. Livedo suggest antiphospholipid antibody syndrome.

This study intents to investigate the prevalence of hypofibrinolysis markers, such as PAI-1 4G/5G and 4G/4G, protein S deficiency, antiphospholipid antibodies and prothrombin G20210A, in psychotic patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 176
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Diagnosis of schizophrenia or schizoaffective disorder by the Semi-structured Interview MINI 5.0.

Exclusion Criteria:

• Inability to provide information.

• Use of illicit drugs.

• Infections such as cerebral toxoplasmosis in HIV seropositive or tertiary syphilis. Patients with "recurrent syphilis" will not be excluded, because false positive tests are common in antiphospholipid antibody syndrome.

Study Design

Observational Model: Case Control, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Insulin Resistance
• Psychosis
• Thrombophilia

Locations

Country	Name	City	State
Brazil	Institudo de Psiquiatria da UFRJ	Rio de Janeiro

Sponsors (2)

Lead Sponsor	Collaborator
Universidade Federal do Rio de Janeiro	Rio de Janeiro State Research Supporting Foundation (FAPERJ)

Country where clinical trial is conducted

Brazil, 

References & Publications (3)

Hoirisch-Clapauch S, Mezzasalma MA, Nardi AE. Pivotal role of tissue plasminogen activator in the mechanism of action of electroconvulsive therapy. J Psychopharmacol. 2014 Feb;28(2):99-105. doi: 10.1177/0269881113507639. Epub 2013 Oct 9. Review. — View Citation

Hoirisch-Clapauch S, Nardi AE. Markers of low activity of tissue plasminogen activator/plasmin are prevalent in schizophrenia patients. Schizophr Res. 2014 Oct;159(1):118-23. doi: 10.1016/j.schres.2014.08.011. Epub 2014 Sep 7. — View Citation

Hoirisch-Clapauch S, Nardi AE. Multiple roles of tissue plasminogen activator in schizophrenia pathophysiology. Semin Thromb Hemost. 2013 Nov;39(8):950-4. doi: 10.1055/s-0033-1357505. Epub 2013 Oct 9. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of hypofibrinolysis markers in psychotic patients	The investigators' hypothesis is that a high prevalence of hypofibrinolysis markers will be probably found in psychotic patients.	One year	No
Secondary	Prevalence of Clinical and Laboratory Markers of Hypofibrinolysis in Patients who Need Electroconvulsive Therapy	The investigators are assessing clinical and laboratory markers of plasminogen activator imbalance in psychiatric patients who require electroconvulsive therapy, specifically patients with major depressive disorders and schizophrenia.	2013-2014	No