Study Using Pregnenolone to Treat Bipolar Depression

Study Overview
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Brief Summary
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Primary purpose of this study is to determine if pregnenolone supplementation is associated with greater improvement in depressive symptoms of patients with bipolar disorder. Also the study will explore possibilities of improving anxiety and manic symptoms as well as the patient's cognition.

Detailed Description
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Determine if pregnenolone supplementation is associated with greater improvement in depressive symptoms than placebo in persons with Bipolar Depression (BPD), depressed phase. In our pilot study, pregnenolone showed a strong signal on depression scores. Secondary Determine if pregnenolone supplementation is associated with greater improvement in anxiety symptoms in persons with BPD, depressed phase. Data from prior studies suggests that pregnenolone may decrease symptoms of anxiety. Anxiety is a common and clinically important feature of BPD. Therefore, we will examine anxiety symptoms in this trial. Determine if pregnenolone supplementation is associated with improvement in manic symptoms as compared to placebo in persons with BPD, depressed phase. Our pilot study suggested that pregnenolone may be associated with improvement in manic symptoms. Although the current study targets bipolar depression we will also examine manic symptoms.

Official Title
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A Randomized, Double Blind, Placebo-controlled Trial of Pregnenolone for Bipolar Depression

Conditions
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Bipolar Disorder, Major Depressive Disorder

Intervention / Treatment
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* Drug: Pregnenolone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and Women of all races age 18-75 years Diagnosis of bipolar I, II or not otherwise specified (NOS) disorders currently meeting criteria for a major depressive episode English speaking Exclusion Criteria: Active suicidal ideation with plan and intent Treatment resistant depression Vulnerable population (i.e. pregnant, cognitively impaired, incarcerated) Severe or life threatening medical condition History of allergic reaction or side effects with prior pregnenolone use Current substance use disorder defined as meeting criteria for abuse or dependence based on the Structured Clinical Interview for the Diagnostic and Statistical Manual (DSM)(SCID) interview and self-reported use within the past 3 months or a positive baseline urine drug screen Removal or addition of concomitant psychiatric medications within 10 days prior to randomization Current Warfarin therapy Current use of oral contraceptives Current hormone replacement therapy History of heart disease or arrhythmias Current (past 7 days) systemic

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pregnenolone<br>This arm will be given 50mg Pregnenolone twice per day for 2 weeks, then 150mg Pregnenolone twice per day for 2 weeks, then 250mg Pregnenolone twice per day for 8 weeks. | Drug: Pregnenolone<br>* Pregnenolone is a naturally occurring neurosteroid that is synthesized from cholesterol in the adrenal glands and central nervous system.<br>* Other names: 3β-hydroxypregn-5-en-20-one;|
| Placebo Comparator: Placebo<br>The arm will be given placebo that matches the Pregnenolone at the same frequency as the Pregnenolone for 12 weeks. | Drug: Placebo<br>* Inactive ingredient matching the active medication in appearance.<br>* Other names: Sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The 17-item Hamilton Rating Scale for Depression (HRSD17) | The HRSD is an observer-rated measure of depressive symptomatology. Minimum: 0; Maximum: 50; Better outcome: lower score; Normal score: 7 or less. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inventory of Depressive Symptomatology-Self Report (IDS-SR) | IDS-SR is a self reported 30 item assessment to diagnose a major depressive episode. Score: Minimum: 0 Maximum: 84 Lower score associated with better outcome | 12 weeks | 
| Young Mania Rating Scale (YMRS) | This is an 11-item, observer rated measure of the severity of manic symptoms on a 5 point scale. The total score indicates overall severity of mania with a minimum of zero (indicating normalcy) and a maximum of 60 (indicating very severe). Score: Minimum: 0 Maximum: 60 Lower score associated with better outcome | 12 weeks | 
| Hamilton Rating Scale for Anxiety (HRSA) | The scale consists of 14 items, each defined by a series of symptoms, and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where less than 17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. | 12 weeks |