Treatment of Bipolar Depression With Pentoxifylline

Early Phase 1CompletedNCT04417049

University Health Network, Toronto6 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Bipolar Depression

Interventions

Pentoxifylline 400 MGDRUG

All patients will be provided with pentoxifylline 400 mg to be orally ingested twice daily for 8 weeks.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Locations (1)

Toronto Western Hospital

Toronto, Ontario, Canada

Outcomes

Primary Outcomes

The recruitment rate

The feasibility of pentoxifylline as a treatment in bipolar disorder will be measured by recruitment rate

Time frame: 8 weeks

The retention rate

The feasibility of pentoxifylline as a treatment in bipolar disorder will be measured by retention rate of the study.

Time frame: 8 weeks

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)

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.

Time frame: 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.

Time frame: 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).

Time frame: 8 weeks

Change in subjective measures of depression using 16-item Quick Inventory for Depressive Symptomology-Self Report (QIDS-SR16) Total Score

Data from ClinicalTrials.gov

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