Clinical trial NCT04417049: Treatment of Bipolar Depression With Pentoxifylline
Official title: Pentoxifylline for Bipolar Depression: A Proof-of-Concept Feasibility Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Bipolar Depression
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2020-06-04
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. Male or female between the age of 18 to 65, inclusive.
3. 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.
4. Patient must present with a moderate to severe depressive episode, as determined by the MADRS score greater than 21.
5. Patient must be receiving guideline-concordant pharmacotherapy without changes in the last month.

Exclusion Criteria:

1. Currently exhibiting symptoms of mania, as determined by the Young Mania Rating Scale (YMRS) score greater than 11.
2. Current symptoms of psychosis or perceptual disturbances of any kind per investigator discretion
3. History of neurological disorders
4. Presence of active suicidality, as determined by the MADRS suicidality item (Item #10) score greater than 4
5. 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.
6. Renal impairment, assessed as creatinine clearance less than 80ml/min
7. Abnormal liver function, assessed as ALT or AST ≥ 3 x ULN or bilirubin ≥ 2 x ULN
8. Severe myocardial infarction
9. Patients with standard contraindications to magnetic resonance imaging (MRI), such as non-MRI compatible implanted metallic devices
10. Patients with a history of cerebrovascular disease or history of intercranial hemorrhage.
11. Laboratory biochemical evidence of abnormal bleeding and/or coagulopathy
12. Pregnant or breastfeeding women. Patients who are sexually active must agree to use a highly effective contraceptive method
13. Use of prohibited concomitant medications

Primary outcomes:
measure: The recruitment rate
timeFrame: 8 weeks
measure: The retention rate
timeFrame: 8 weeks
Secondary outcomes:
measure: Safety will be assessed using patient-reported treatment emergent adverse events.
timeFrame: 8 weeks
measure: Change in depression severity using the Montgomery Asberg Depression Rating Scale (MADRS)
timeFrame: 8 weeks
measure: Change in cerebral blood flow using ASL MRI imaging
timeFrame: 8 weeks
measure: Change in inflammatory markers using blood serum and plasma
timeFrame: 8 weeks
measure: Change in subjective measures of depression using 16-item Quick Inventory for Depressive Symptomology-Self Report (QIDS-SR16) Total Score
timeFrame: 8 weeks
measure: Changes in subjective measures of cognition using the Perceived Deficits Questionnaire for Depression-5 item (PDQ-5-D)
timeFrame: 8 weeks
measure: Changes in psychomotor speed, concentration and memory using the Digit Symbols Substitution Task (DSST)
timeFrame: 8 weeks
measure: Change in attention and concentration using the Trails Making Tests
timeFrame: 8 weeks
measure: Change in verbal fluency using the FAS test
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
Study officials:
affiliation: Psychiatry
name: Joshua D Rosenblat, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: