Treatment of Bipolar Depression With Pentoxifylline

NCT ID: NCT04417049

Last Updated: 2022-04-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-12
• Study Completion Date: 2021-11-29

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.

Conditions

Bipolar Depression

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pentoxifylline

Group Type: EXPERIMENTAL

Pentoxifylline 400 MG

Intervention Type: DRUG

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

Interventions

Pentoxifylline 400 MG

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

Intervention Type: DRUG

Other Intervention Names

Trental

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Joshua Rosenblat

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joshua D Rosenblat, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Psychiatry

Locations

Toronto Western Hospital

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

20-5219

Identifier Type: -

Identifier Source: org_study_id