Treatment of Bipolar Depression With Pentoxifylline (PTX-BD)

University Health Network, Toronto

Status and phase: Completed; Early Phase 1

Conditions: Bipolar Depression

Treatments: Drug: Pentoxifylline 400 MG

Study type: Interventional

Funder types: Other

Identifiers

NCT04417049

20-5219

Details and patient eligibility

About

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.

Full 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.

Enrollment: 6 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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6 participants in 1 patient group

Pentoxifylline

Experimental group

Treatment:

Drug: Pentoxifylline 400 MG