Bipolar DepressionEarly Phase 1PTX-BDNCT04417049
Treatment of Bipolar Depression With Pentoxifylline
A Early Phase 1 study testing Pentoxifylline 400 MG in people with Bipolar Depression, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
Growing theoretical and clinical evidence has suggested that pentoxifylline may have an effect in improving depressive symptoms. Herein, we aim to evaluate the effect of pentoxifylline in patients with bipolar depression over an 8-week trial. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Bipolar Depression
- What is being tested?
- Pentoxifylline 400 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteCanada
- Study dates
- 12 Jul 2021to 29 Nov 2021
- Phase
- Early Phase 1
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provide written, voluntary informed consent prior to study enrollment. Substitute decision makers will not be allowed to consent to study on a potential patients behalf.
- Male or female between the age of 18 to 65, inclusive.
- Meets DSM-5 criteria for Bipolar I or II Disorder, currently experiencing a Major Depressive Episode. Diagnosis will be confirmed using the Mini-International Neuropsychiatric Interview (MINI) conducted by a delegated physician or trained research study while assessing eligibility.
- Patient must present with a moderate to severe depressive episode, as determined by the MADRS score greater than 21.
- Patient must be receiving guideline-concordant pharmacotherapy without changes in the last month.
Who cannot join
- Currently exhibiting symptoms of mania, as determined by the Young Mania Rating Scale (YMRS) score greater than 11.
- Current symptoms of psychosis or perceptual disturbances of any kind per investigator discretion
- History of neurological disorders
- Presence of active suicidality, as determined by the MADRS suicidality item (Item #10) score greater than 4
- Presence of a contraindication to PTX, including a drug allergy or allergy to xanthine derivatives, low or labile blood pressure, acute myocardial infarction, cardiac arrhythmia, peptic ulcers, coronary artery disease or coagulation disorder.
- Renal impairment, assessed as creatinine clearance less than 80ml/min
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- Abnormal liver function, assessed as ALT or AST ≥ 3 x ULN or bilirubin ≥ 2 x ULN
- Severe myocardial infarction
- Patients with standard contraindications to magnetic resonance imaging (MRI), such as non-MRI compatible implanted metallic devices
- Patients with a history of cerebrovascular disease or history of intercranial hemorrhage.
- Laboratory biochemical evidence of abnormal bleeding and/or coagulopathy
- Pregnant or breastfeeding women. Patients who are sexually active must agree to use a highly effective contraceptive method
- Use of prohibited concomitant medications
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pentoxifylline for Bipolar Depression: A Proof-of-Concept Feasibility Study
Growing theoretical and clinical evidence has suggested that pentoxifylline may have an effect in improving depressive symptoms. Herein, we aim to evaluate the effect of pentoxifylline in patients with bipolar depression over an 8-week trial.
Read the detailed description
Growing evidence has demonstrated that inflammation and alterations in cerebral blood flow (CBF) contribute to the pathophysiology of bipolar depression (BD). Pentoxifylline is a phosphodiesterase inhibitor that improves CBF and has potent anti-inflammatory and antioxidant effects. We therefore hypothesize that pentoxifylline may have antidepressant effects in BD. We will conduct an 8-week, open-label, single-armed, feasibility study assessing clinical and neurobiological effects of adjunctive pentoxifylline in the acute treatment of BD. Feasibility will be determined by evaluating recruitment/retention rates, target engagement (e.g., changes in biomarkers with pentoxifylline treatment) and preliminary efficacy testing with 6 participants. Evaluating pentoxifylline's effects may further our understanding of BD pathophysiology and help identify novel treatment targets.
- Conditions
- Bipolar Depression
- Being tested
- Pentoxifylline 400 MG
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pentoxifylline 400 MGDrug
Also called Trental
All patients will be provided with pentoxifylline 400 mg to be orally ingested twice daily for 8 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Pentoxifylline | Experimental | Not described Receives: Drug: Pentoxifylline 400 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
The recruitment rate
The feasibility of pentoxifylline as a treatment in bipolar disorder will be measured by recruitment rate
Measured: 8 weeks
The retention rate
The feasibility of pentoxifylline as a treatment in bipolar disorder will be measured by retention rate of the study.
Measured: 8 weeks
Secondary outcomes (9)
Safety will be assessed using patient-reported treatment emergent adverse events.
Measured: 8 weeks
Change in depression severity using the Montgomery Asberg Depression Rating Scale (MADRS)
The MADRS is a clinician-rated scale measuring depression severity. It consists of 10 items, each scored from 0 (normal) to 6 (severe), for a total possible score of 60. A higher score is indicative of greater depressive severity Response rates are defined as ≥ 50% decrease and Remission ≤ 10 actual score.
Measured: 8 weeks
Change in cerebral blood flow using ASL MRI imaging
Patients will complete an MRI sequence called arterial spin labelling (ASL) at baseline and week 8 to look at changes in cerebral blood flow before and after treatment. ASL does not use any contrast or radiation.
Measured: 8 weeks
Change in inflammatory markers using blood serum and plasma
Blood will be collected in order to evaluate changes in inflammatory biomarkers associated with depressive disorders (e.g., TNF-alpha, IL-1 and IL-6).
Measured: 8 weeks
Change in subjective measures of depression using 16-item Quick Inventory for Depressive Symptomology-Self Report (QIDS-SR16) Total Score
Patients will complete a brief self-reported scale that measures subjective symptoms of depression. In total there are 16 items, each scored from 0 to 3. The total score ranges from 0 to 27, with higher scores indicating worse depressive severity.
Measured: 8 weeks
Changes in subjective measures of cognition using the Perceived Deficits Questionnaire for Depression-5 item (PDQ-5-D)
The PDQ-5 is a brief patient-rated scale to assess subjective cognitive dysfunction in people with depression. The PDQ originally is a 20-item questionnaire that generates a total score and 4 subscale scores in 4 cognitive domains: attention/concentration, retrospective memory, prospective memory, and planning/organization. The 5-item version (PDQ-D-5) is derived from the 20-item version and provides a validated measure of perceived cognitive deficits in depressive disorders.
Measured: 8 weeks
Changes in psychomotor speed, concentration and memory using the Digit Symbols Substitution Task (DSST)
The DSST is used to evaluate psychomotor speed and concentration. It consists of multiple digits with unique symbols associated with each digit. Patients are asked to substitute each digit with the correct symbol in 90 seconds. Each correct symbol is counted to calculate the total score
Measured: 8 weeks
Change in attention and concentration using the Trails Making Tests
Trail Making Test (TMT) is a cognitive test designed to assess attention and concentration through visuomotor tracking, executive function, and cognitive flexibility. It consists of two parts, A and B. In part A, a line is drawn between consecutive numbers. In part B a line is drawn alternating between numbers and letters. Score is calculated through total time to completion of each part, with higher times indicating impairment.
Measured: 8 weeks
Change in verbal fluency using the FAS test
Change in verbal fluency (i.e., semantic and animal naming) will be measured by using the Controlled Oral Word Association Test. Scores will be assessed through the total number of words stated in a given letter or category in a time period of one minute. Number of repetitions and intrusions will also be measured.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2020
- Study start12 Jul 2021
- Primary completion3 Nov 2021
- Study completion29 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bipolar DepressionStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Joshua Rosenblat, University Health Network, Toronto
- Investigators
- Joshua D Rosenblat, MD, MSc, Principal investigator, Psychiatry
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04417049
- Sponsor's protocol ID
- 20-5219
- Acronym
- PTX-BD
- Status last verified
- Apr 2022
- First submitted
- 2 Jun 2020
- Last updated
- 15 Apr 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pentoxifylline for Bipolar Depression: A Proof-of-Concept Feasibility Study
- ClinicalTrials.gov ID
- NCT04417049
- Acronym / sponsor ID
- PTX-BD / 20-5219
- Conditions
- Bipolar Depression
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- 12 Jul 2021 (actual)
- Primary completion
- 3 Nov 2021 (actual)
- Study completion
- 29 Nov 2021 (actual)
- First posted
- 4 Jun 2020 (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.
Growing theoretical and clinical evidence has suggested that pentoxifylline may have an effect in improving depressive symptoms. Herein, we aim to evaluate the effect of pentoxifylline in patients with bipolar depression over an 8-week trial.
Detailed description
Growing evidence has demonstrated that inflammation and alterations in cerebral blood flow (CBF) contribute to the pathophysiology of bipolar depression (BD). Pentoxifylline is a phosphodiesterase inhibitor that improves CBF and has potent anti-inflammatory and antioxidant effects. We therefore hypothesize that pentoxifylline may have antidepressant effects in BD. We will conduct an 8-week, open-label, single-armed, feasibility study assessing clinical and neurobiological effects of adjunctive pentoxifylline in the acute treatment of BD. Feasibility will be determined by evaluating recruitment/retention rates, target engagement (e.g., changes in biomarkers with pentoxifylline treatment) and preliminary efficacy testing with 6 participants. Evaluating pentoxifylline's effects may further our understanding of BD pathophysiology and help identify novel treatment targets.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pentoxifylline | Experimental | Drug: Pentoxifylline 400 MG |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Provide written, voluntary informed consent prior to study enrollment. Substitute decision makers will not be allowed to consent to study on a potential patients behalf.
- Male or female between the age of 18 to 65, inclusive.
- Meets DSM-5 criteria for Bipolar I or II Disorder, currently experiencing a Major Depressive Episode. Diagnosis will be confirmed using the Mini-International Neuropsychiatric Interview (MINI) conducted by a delegated physician or trained research study while assessing eligibility.
- Patient must present with a moderate to severe depressive episode, as determined by the MADRS score greater than 21.
- Patient must be receiving guideline-concordant pharmacotherapy without changes in the last month.
Key exclusion criteria (13 listed)
- Currently exhibiting symptoms of mania, as determined by the Young Mania Rating Scale (YMRS) score greater than 11.
- Current symptoms of psychosis or perceptual disturbances of any kind per investigator discretion
- History of neurological disorders
- Presence of active suicidality, as determined by the MADRS suicidality item (Item #10) score greater than 4
- Presence of a contraindication to PTX, including a drug allergy or allergy to xanthine derivatives, low or labile blood pressure, acute myocardial infarction, cardiac arrhythmia, peptic ulcers, coronary artery disease or coagulation disorder.
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 |
|---|---|---|
| Pentoxifylline 400 MGAlso: TrentalAll patients will be provided with pentoxifylline 400 mg to be orally ingested twice daily for 8 weeks. | Drug | Pentoxifylline |
Primary outcome
The recruitment rate
Time frame: 8 weeks
The feasibility of pentoxifylline as a treatment in bipolar disorder will be measured by recruitment rate
The retention rate
Time frame: 8 weeks
The feasibility of pentoxifylline as a treatment in bipolar disorder will be measured by retention rate of the study.
9 secondary outcomes
Safety will be assessed using patient-reported treatment emergent adverse events.
Time frame: 8 weeks
Change in depression severity using the Montgomery Asberg Depression Rating Scale (MADRS)
Time frame: 8 weeks
Change in cerebral blood flow using ASL MRI imaging
Time frame: 8 weeks
Change in inflammatory markers using blood serum and plasma
Time frame: 8 weeks
Change in subjective measures of depression using 16-item Quick Inventory for Depressive Symptomology-Self Report (QIDS-SR16) Total Score
Time frame: 8 weeks
Changes in subjective measures of cognition using the Perceived Deficits Questionnaire for Depression-5 item (PDQ-5-D)
Time frame: 8 weeks
Changes in psychomotor speed, concentration and memory using the Digit Symbols Substitution Task (DSST)
Time frame: 8 weeks
Change in attention and concentration using the Trails Making Tests
Time frame: 8 weeks
Change in verbal fluency using the FAS test
Time frame: 8 weeks
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 15 Apr 2022.
- Individual participant dataSharing planned: No
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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.
Joshua D Rosenblat, MD, MSc principal investigator
Psychiatry
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Pentoxifylline 400 MG in people with Bipolar Depression, run by University Health Network, Toronto at 1 site in Canada.
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 5 inclusion and 13 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 15 Apr 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 Canada. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
The recruitment rate (time frame: 8 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Apr 2022.