Back to resultsTreatment of Bipolar Depression With Pentoxifylline (PTX-BD)
Primary Purpose
Bipolar Depression
Status
Completed
Phase
Early Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Pentoxifylline 400 MG
Sponsored by
About this trial
This is an interventional treatment trial for Bipolar Depression
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
- 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
Sites / Locations
- Toronto Western Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Pentoxifylline
Arm Description
Outcomes
Primary Outcome Measures
The recruitment rate
The feasibility of pentoxifylline as a treatment in bipolar disorder will be measured by recruitment rate
The retention rate
The feasibility of pentoxifylline as a treatment in bipolar disorder will be measured by retention rate of the study.
Secondary Outcome Measures
Safety will be assessed using patient-reported treatment emergent adverse events.
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.
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.
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).
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.
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.
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
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.
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.
Full Information
NCT ID
NCT04417049
First Posted
June 2, 2020
Last Updated
April 13, 2022
Sponsor
University Health Network, Toronto
1. Study Identification
Unique Protocol Identification Number
NCT04417049
Brief Title
Treatment of Bipolar Depression With Pentoxifylline
Acronym
PTX-BD
Official Title
Pentoxifylline for Bipolar Depression: A Proof-of-Concept Feasibility Study
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
July 12, 2021 (Actual)
Primary Completion Date
November 3, 2021 (Actual)
Study Completion Date
November 29, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Health Network, Toronto
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bipolar Depression
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pentoxifylline
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Pentoxifylline 400 MG
Other Intervention Name(s)
Trental
Intervention Description
All patients will be provided with pentoxifylline 400 mg to be orally ingested twice daily for 8 weeks.
Primary Outcome Measure Information:
Title
The recruitment rate
Description
The feasibility of pentoxifylline as a treatment in bipolar disorder will be measured by recruitment rate
Time Frame
8 weeks
Title
The retention rate
Description
The feasibility of pentoxifylline as a treatment in bipolar disorder will be measured by retention rate of the study.
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Safety will be assessed using patient-reported treatment emergent adverse events.
Time Frame
8 weeks
Title
Change in depression severity using the Montgomery Asberg Depression Rating Scale (MADRS)
Description
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
Title
Change in cerebral blood flow using ASL MRI imaging
Description
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
Title
Change in inflammatory markers using blood serum and plasma
Description
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
Title
Change in subjective measures of depression using 16-item Quick Inventory for Depressive Symptomology-Self Report (QIDS-SR16) Total Score
Description
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.
Time Frame
8 weeks
Title
Changes in subjective measures of cognition using the Perceived Deficits Questionnaire for Depression-5 item (PDQ-5-D)
Description
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.
Time Frame
8 weeks
Title
Changes in psychomotor speed, concentration and memory using the Digit Symbols Substitution Task (DSST)
Description
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
Time Frame
8 weeks
Title
Change in attention and concentration using the Trails Making Tests
Description
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.
Time Frame
8 weeks
Title
Change in verbal fluency using the FAS test
Description
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.
Time Frame
8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joshua D Rosenblat, MD, MSc
Organizational Affiliation
Psychiatry
Official's Role
Principal Investigator
Facility Information:
Facility Name
Toronto Western Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T 2S8
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Treatment of Bipolar Depression With Pentoxifylline
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