Pentoxifylline Add-on Therapy for Schizophrenia

Pentoxifylline Add-on Therapy for Schizophrenia: A Randomized, Placebo-controlled, Double-blind Trial

The etiology and pathogenesis of schizophrenia remain unclear. The immune dysfunction hypothesis for schizophrenia has attracted increasing attention from researchers, and substantial evidence suggested that the levels of TNF-α and other cytokines are markedly elevated in patients with schizophrenia. The investigators aim to evaluate the adjuvant therapeutic effect of Pentoxifylline, a TNF-α inhibitor that crosses the blood-brain barrier, in a randomized, double-blind, 6-week trial. Individuals with schizophrenia will receive either Pentoxifylline or a matching placebo as an add-on treatment to antipsychotic agents. Subjects' positive and negative symptoms and plasma concentration of neuroinflammatory markers will be monitored at baseline and every two weeks until the end of the trial.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Oxopurin

Detailed Description

Ninety schizophrenic patients will be randomized to a Pentoxifylline (400 mg twice a day) or placebo treatment for six weeks. Pentoxifylline and placebo will be added to the current antipsychotic drug treatment. Participants will be asked to fill a socio-demographic questionnaire and to undergo a clinical differential diagnosis using the Symptoms Check List (SCL)-90, Clinical Global Impression (CGI), positive and negative symptoms scale (PANSS), and Hamilton depression rating scale (HAM-D). Following baseline evaluation, participants will be monitored for symptoms every two weeks until the end of the trial (overall three visits) using CGI, PANSS, and HAM-D. Adverse effects will be documented every visit using the Treatment Emergent Symptom Scale. Finally, yet importantly, a blood sample will be collected at baseline and every two weeks until the end of the trial to study the treatment effect on inflammatory markers.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Alon Shamir, Ph.D.; Phone Number: +97249954708; Email: alons@mazor.health.gov.il

Study Locations

• Israel
  • Akko, Israel, 25201
    • Recruiting
    • Mazor MHC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients meeting the DSM-V criteria for schizophrenia spectrum disorders.
2. Clinical Global Impression (CGI) score ≥ 4 and ≤ 6 at screening.
3. Initiated treatment with a stable dosage of typical and/or atypical antipsychotic medication for at least four weeks.

Exclusion Criteria:

1. Previous sensitivity to pentoxifylline (PTF).
2. Chronic immune and/or inflammatory diseases (such as rheumatoid arthritis, systemic lupus erythematosus, chronic inflammatory bowel disease).
3. Consumption for > 3 consecutive days of any immune-modulating or anti-inflammatory drug in the last month.
4. Current active and persistent substance and/or alcohol abuse.
5. Any severe, unstable medical condition (e.g., cardiovascular disorders, diabetes mellitus, respiratory diseases, cancer).
6. Obesity (body mass index > 30).
7. Cognitive dysfunction such as retardation.
8. Known or suspected pregnancy or breastfeeding women.
9. Lactose intolerance or sensitivity.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pentoxifylline; Pentoxifylline (Oxopurin 400 mg)	Drug: Oxopurin; Subjects will receive two capsules per day.; Other Names: Pentoxifylline
Placebo Comparator: Placebo; Placebo (105 mg Lactose and 510 mg Dextrose)	Drug: Oxopurin; Subjects will receive two capsules per day.; Other Names: Pentoxifylline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive and negative symptoms	Improvement in positive and negative symptoms (Changes in PANSS rates)	Subjects will be monitored at baseline and every two weeks for six weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depressive symptoms	Changes in HAM-D rates	Subjects will be monitored at baseline and every two weeks for six weeks

Collaborators and Investigators

• Sponsor: Mazra Mental Health Center
• Collaborators: Ben-Gurion University of the Negev

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2019
• Primary Completion (Anticipated): April 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: September 29, 2021
• First Submitted That Met QC Criteria: September 29, 2021
• First Posted (Actual): October 11, 2021

Study Record Updates

• Last Update Posted (Actual): October 11, 2021
• Last Update Submitted That Met QC Criteria: September 29, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Antioxidants; Phosphodiesterase Inhibitors; Free Radical Scavengers; Radiation-Protective Agents; Pentoxifylline
• Other Study ID Numbers: 03-019-MZR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No