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Pentoxifylline as an Adjunctive in Treatment of Negative Symptoms in Chronic Schizophrenia

Phase 1
Completed
Conditions
Schizophrenia
Interventions
Drug: Placebo oral tablet
Registration Number
NCT04094207
Lead Sponsor
Sadat City University
Brief Summary

The aim of this study to evaluate the efficacy and safety of pentoxifylline, the novel phosphodiesterase inhibitor, as an adjunctive to risperidone in alleviating the negative symptoms of schizophrenia.

Detailed Description

there is some evidence for the role of phosphodiesterase (PDE) signaling system in pathophysiology of schizophrenia making this system a potential target for therapeutic agents. PDEs are a family of enzymes that hydrolyse cyclic nucleotides and thus play a key role in regulating intracellular levels of the second messenger cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate. Pentoxifylline (PTX) is a methylated xanthine derivative and a PDE inhibitor that is FDA-approved for the treatment of patients with intermittent claudication on the basis of chronic occlusive arterial disease of the limbs. It is known to inhibit platelet aggregation, increase erythrocyte flexibility or deformability, and reduce blood viscosity. The rationale for its use in schizophrenia is that it competitively inhibits PDEs, resulting in increased cAMP levels, the activation of protein kinase A (PKA), the inhibition of IL and TNF-α synthesis, and reduced inflammation. Furthermore, there is growing evidence to support the inflammatory hypothesis of schizophrenia, the investigators will also explore whether cytokine levels mediate the response from pentoxifylline treatment.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
80
Inclusion Criteria
  • Ages between 18-40 years
  • Males & females
  • patients between the ages of 18 and 53 who met the diagnostic criteria for schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (20), with a minimum disease duration of two years.
  • stable on risperidone for a minimum of 8 weeks
  • clinically stable for at least 4 weeks prior to study.
  • willing to give informed consent.
  • able to take medication orally.
Exclusion Criteria
  • Acute, unstable, significant or untreated medical illness beside schizophrenia;
  • Pregnant or breast-feeding females;
  • History of substance abuse or dependence in the past 3 months.
  • Known contraindication to pentoxifylline treatment.
  • Any serious or life-threatening medical conditions or neurological problem, severe extrapyramidal symptoms, history of abnormal bleeding, presence of hypothyroidism, renal disease, cardiovascular problems, rising liver transaminases to 3 times the upper limit of normal or higher

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Pentoxifylline groupPentoxifyllinePentoxifylline will be given orally at 800 mg a day for 8 weeks
Control groupPlacebo oral tabletEquivalent Placebo will be given
Primary Outcome Measures
NameTimeMethod
Treatment-induced change in total score on Positive and Negative Syndrome Scale (PANSS)Baseline to week 8 of the study

PANSS total score will be used to examine treatment-induced change in psychaopthology. The PANSS is a 30-item rating scale used to assess symptoms of psychopathology. We will use the total PANSS score as the primary outcome measure which reflects total level of psychopathology including the positive and negative symptoms as well as general psychopathology.This measure will be administered at baseline, week 8 and week 16 of the study to assess if pentoxifylline treatment results in a significant reduction in PANSS total score as opposed to placebo.

Secondary Outcome Measures
NameTimeMethod
Treatment-induced changes in plasma level of cytokinesBaseline and week 8 of the study

Cytokine levels will assessed at baseline and week 8 of the study to examine treatment-induced changes in neuroinflammation.

Trial Locations

Locations (1)

Faculty of Medicine

🇪🇬

Shibīn Al Kawm, Egypt

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