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

NCT ID: NCT04094207

Last Updated: 2022-10-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-01
• Study Completion Date: 2022-09-30

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.

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Control group

Equivalent Placebo will be given

Group Type: PLACEBO_COMPARATOR

Placebo oral tablet

Intervention Type: DRUG

Placebo tablets PLUS Risperidone 2 mg tablet up to 6 mg/day

Pentoxifylline group

Pentoxifylline will be given orally at 800 mg a day for 8 weeks

Group Type: EXPERIMENTAL

Pentoxifylline

Intervention Type: DRUG

Pentoxifylline tablet PLUS Risperidone 2 mg tablet up to 6 mg/day

Interventions

Placebo oral tablet

Placebo tablets PLUS Risperidone 2 mg tablet up to 6 mg/day

Intervention Type: DRUG

Pentoxifylline

Pentoxifylline tablet PLUS Risperidone 2 mg tablet up to 6 mg/day

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Sadat City University

OTHER

Sponsor Role: lead

Responsible Party

Mahmoud Samy Abdallah

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Faculty of Medicine

Shibīn al Kawm, , Egypt

Countries

Egypt

References

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.

Reference Type: DERIVED

PMID: 36341700 (View on PubMed)

Other Identifiers

4/2021NEUR1

Identifier Type: -

Identifier Source: org_study_id