Clinical trial NCT05073640: Pentoxifylline Add-on Therapy for Schizophrenia
Official title: Pentoxifylline Add-on Therapy for Schizophrenia: A Randomized, Placebo-controlled, Double-blind Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Schizophrenia
Lead sponsor: Mazra Mental Health Center
Sponsor class: OTHER
Collaborators: name: Ben-Gurion University of the Negev
First posted: 2021-10-11
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Positive and negative symptoms
timeFrame: Subjects will be monitored at baseline and every two weeks for six weeks
Secondary outcomes:
measure: Depressive symptoms
timeFrame: Subjects will be monitored at baseline and every two weeks for six weeks
Other outcomes:
Locations:
city: Akko
country: Israel
facility: Mazor MHC
Study officials:
References: