Clinical trial NCT04094207: Pentoxifylline as an Adjunctive in Treatment of Negative Symptoms in Chronic Schizophrenia
Official title: The Phosphodiesterase Inhibitor Pentoxifylline as an Adjunctive in Treatment of Negative Symptoms in Chronic Schizophrenia: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Schizophrenia
Lead sponsor: Sadat City University
Sponsor class: OTHER
First posted: 2019-09-18
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Treatment-induced change in total score on Positive and Negative Syndrome Scale (PANSS)
timeFrame: Baseline to week 8 of the study
Secondary outcomes:
measure: Treatment-induced changes in plasma level of cytokines
timeFrame: Baseline and week 8 of the study
Other outcomes:
Locations:
city: Shibīn Al Kawm
country: Egypt
facility: Faculty of Medicine
Study officials:
References:
citation: Abdallah MS, Mosalam EM, Hassan A, Ramadan AN, Omara-Reda H, Zidan AA, Samman WA, El-Berri EI. Pentoxifylline as an adjunctive in treatment of negative symptoms in chronic schizophrenia: A double-blind, randomized, placebo-controlled trial. CNS Neurosci Ther. 2023 Jan;29(1):354-364. doi: 10.1111/cns.14010. Epub 2022 Nov 7.