Pentoxifylline as an Adjunctive in Treatment of Negative Symptoms in Chronic Schizophrenia
Primary Purpose
Schizophrenia
Status
Completed
Phase
Phase 1
Locations
Egypt
Study Type
Interventional
Intervention
Placebo oral tablet
Pentoxifylline
Sponsored by
About this trial
This is an interventional treatment trial for Schizophrenia
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
Sites / Locations
- Faculty of Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Control group
Pentoxifylline group
Arm Description
Equivalent Placebo will be given
Pentoxifylline will be given orally at 800 mg a day for 8 weeks
Outcomes
Primary Outcome Measures
Treatment-induced change in total score on Positive and Negative Syndrome Scale (PANSS)
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
Treatment-induced changes in plasma level of cytokines
Cytokine levels will assessed at baseline and week 8 of the study to examine treatment-induced changes in neuroinflammation.
Full Information
NCT ID
NCT04094207
First Posted
September 15, 2019
Last Updated
October 23, 2022
Sponsor
Sadat City University
1. Study Identification
Unique Protocol Identification Number
NCT04094207
Brief Title
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
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
January 1, 2019 (Actual)
Primary Completion Date
September 30, 2021 (Actual)
Study Completion Date
September 30, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sadat City University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
80 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Control group
Arm Type
Placebo Comparator
Arm Description
Equivalent Placebo will be given
Arm Title
Pentoxifylline group
Arm Type
Experimental
Arm Description
Pentoxifylline will be given orally at 800 mg a day for 8 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo oral tablet
Intervention Description
Placebo tablets PLUS Risperidone 2 mg tablet up to 6 mg/day
Intervention Type
Drug
Intervention Name(s)
Pentoxifylline
Intervention Description
Pentoxifylline tablet PLUS Risperidone 2 mg tablet up to 6 mg/day
Primary Outcome Measure Information:
Title
Treatment-induced change in total score on Positive and Negative Syndrome Scale (PANSS)
Description
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.
Time Frame
Baseline to week 8 of the study
Secondary Outcome Measure Information:
Title
Treatment-induced changes in plasma level of cytokines
Description
Cytokine levels will assessed at baseline and week 8 of the study to examine treatment-induced changes in neuroinflammation.
Time Frame
Baseline and week 8 of the study
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Facility Information:
Facility Name
Faculty of Medicine
City
Shibīn Al Kawm
Country
Egypt
12. IPD Sharing Statement
Plan to Share IPD
Yes
Citations:
PubMed Identifier
36341700
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.
Results Reference
derived
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Pentoxifylline as an Adjunctive in Treatment of Negative Symptoms in Chronic Schizophrenia
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