SchizophreniaPhase 1/2NCT04094207
Pentoxifylline as an Adjunctive in Treatment of Negative Symptoms in Chronic Schizophrenia
A Phase 1/2 study testing Pentoxifylline in people with Schizophrenia, run by Sadat City University at 1 site in Egypt.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Pentoxifylline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Jan 2019to 30 Sep 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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
- Being tested
- Placebo oral tablet, Pentoxifylline
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo oral tabletDrug
Placebo tablets PLUS Risperidone 2 mg tablet up to 6 mg/day
PentoxifyllineDrug
Pentoxifylline tablet PLUS Risperidone 2 mg tablet up to 6 mg/day
| Study group | Role | What they receive |
|---|---|---|
| Control group | Placebo comparator | Equivalent Placebo will be given Receives: Drug: Placebo oral tablet |
| Pentoxifylline group | Experimental | Pentoxifylline will be given orally at 800 mg a day for 8 weeks Receives: Drug: Pentoxifylline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to week 8 of the study
Secondary outcomes (1)
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.
Measured: Baseline and week 8 of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2019
- Study start1 Jan 2019
- Primary completion30 Sep 2021
- Study completion30 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sadat City University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mahmoud Samy Abdallah, Sadat City University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04094207
- Sponsor's protocol ID
- 4/2021NEUR1
- Status last verified
- Oct 2022
- First submitted
- 15 Sep 2019
- Last updated
- 25 Oct 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
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.
PubMed 36341700
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04094207
- Acronym / sponsor ID
- 4/2021NEUR1
- Conditions
- Schizophrenia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Sadat City UniversityUniversity, hospital or other
- Study start
- 1 Jan 2019 (actual)
- Primary completion
- 30 Sep 2021 (actual)
- Study completion
- 30 Sep 2022 (actual)
- First posted
- 18 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control group | Placebo comparator | Drug: Placebo oral tabletEquivalent Placebo will be given |
| Pentoxifylline group | Experimental | Drug: PentoxifyllinePentoxifylline will be given orally at 800 mg a day for 8 weeks |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo oral tabletPlacebo tablets PLUS Risperidone 2 mg tablet up to 6 mg/day | Drug | Control group |
| PentoxifyllinePentoxifylline tablet PLUS Risperidone 2 mg tablet up to 6 mg/day | Drug | Pentoxifylline group |
Primary outcome
Treatment-induced change in total score on Positive and Negative Syndrome Scale (PANSS)
Time frame: Baseline to week 8 of the study
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.
1 secondary outcome
Treatment-induced changes in plasma level of cytokines
Time frame: Baseline and week 8 of the study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2022.
- Derived from this study: PubMed 36341700Abdallah 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.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pentoxifylline in people with Schizophrenia, run by Sadat City University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment-induced change in total score on Positive and Negative Syndrome Scale (PANSS) (time frame: Baseline to week 8 of the study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04094207, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2022; AzTrials last refreshed its copy on 8 Nov 2026.