Bipolar Disorder, Major Depressive Disorder
Conditions
Brief summary
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
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 1. 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. 2. 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.
Interventions
DRUGPregnenolone
Pregnenolone is a naturally occurring neurosteroid that is synthesized from cholesterol in the adrenal glands and central nervous system.
DRUGPlacebo
Inactive ingredient matching the active medication in appearance.
Sponsors
Stanley Medical Research Institute
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The 17-item Hamilton Rating Scale for Depression (HRSD17) | 12 weeks | The HRSD is an observer-rated measure of depressive symptomatology. Minimum: 0; Maximum: 50; Better outcome: lower score; Normal score: 7 or less. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Inventory of Depressive Symptomatology-Self Report (IDS-SR) | 12 weeks | 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 |
| Young Mania Rating Scale (YMRS) | 12 weeks | 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 |
| Hamilton Rating Scale for Anxiety (HRSA) | 12 weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pregnenolone 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.
Pregnenolone: Pregnenolone is a naturally occurring neurosteroid that is synthesized from cholesterol in the adrenal glands and central nervous system. | 38 |
| Placebo The arm will be given placebo that matches the Pregnenolone at the same frequency as the Pregnenolone for 12 weeks.
Placebo: Inactive ingredient matching the active medication in appearance. | 35 |
| Total | 73 |
Baseline characteristics
| Characteristic | Placebo | Total | Pregnenolone |
|---|---|---|---|
| Age, Continuous | 44.1 years STANDARD_DEVIATION 10.4 | 43.6 years STANDARD_DEVIATION 9.5 | 43.2 years STANDARD_DEVIATION 8.5 |
| Age of onset of mood symptoms | 26.7 years STANDARD_DEVIATION 7.3 | 26.7 years STANDARD_DEVIATION 8.22 | 26.4 years STANDARD_DEVIATION 9 |
| Bipolar Diagnosis Bipolar I | 15 participants | 31 participants | 16 participants |
| Bipolar Diagnosis Bipolar II | 17 participants | 38 participants | 21 participants |
| Bipolar Diagnosis Bipolar Not Otherwise Specified | 3 participants | 4 participants | 1 participants |
| Concomitant Medications: Anticonvulsant Anticonvulsants | 10 participants | 20 participants | 10 participants |
| Concomitant Medications: Anticonvulsant No anticonvulsants | 25 participants | 53 participants | 28 participants |
| Concomitant Medications: Antidepressant Antidepressants | 22 participants | 43 participants | 21 participants |
| Concomitant Medications: Antidepressant No antidepressants | 13 participants | 30 participants | 17 participants |
| Concomitant Medications: Antipsychotic Antipsychotic | 18 participants | 35 participants | 17 participants |
| Concomitant Medications: Antipsychotic No antipsychotic | 17 participants | 38 participants | 21 participants |
| Concomitant Medications: Lithium Lithium | 4 participants | 9 participants | 5 participants |
| Concomitant Medications: Lithium No Lithium | 31 participants | 64 participants | 33 participants |
| Concomitant medications: None Concomitant medication | 29 participants | 60 participants | 31 participants |
| Concomitant medications: None No concomitant medications | 6 participants | 13 participants | 7 participants |
| Concomitant Medications: Sedative/hypnotic/anxiolytic No Sedative/hypnotic/anxiolytic | 15 participants | 37 participants | 22 participants |
| Concomitant Medications: Sedative/hypnotic/anxiolytic Sedative/hypnotic/anxiolytic | 20 participants | 36 participants | 16 participants |
| Concomitant medications: Stimulant No stimulant | 34 participants | 72 participants | 38 participants |
| Concomitant medications: Stimulant Stimulant | 1 participants | 1 participants | 0 participants |
| Hamilton Rating Scale for Anxiety (HRSA) | 22.8 units on a scale STANDARD_DEVIATION 8.1 | 21.1 units on a scale STANDARD_DEVIATION 9.2 | 19.4 units on a scale STANDARD_DEVIATION 9.8 |
| Hamilton Rating Scale for Depression (HRSD) | 23.5 units on a scale STANDARD_DEVIATION 4.6 | 22.4 units on a scale STANDARD_DEVIATION 4.3 | 21.3 units on a scale STANDARD_DEVIATION 4 |
| Inventory of Depressive Symtomatology-Self Report (IDS-SR) | 47.5 units on a scale STANDARD_DEVIATION 14.5 | 42.7 units on a scale STANDARD_DEVIATION 15.2 | 38.0 units on a scale STANDARD_DEVIATION 14.5 |
| Race/Ethnicity, Customized African-American | 15 participants | 33 participants | 18 participants |
| Race/Ethnicity, Customized Caucasian | 16 participants | 34 participants | 18 participants |
| Race/Ethnicity, Customized Hispanic | 4 participants | 6 participants | 2 participants |
| Sex: Female, Male Female | 24 Participants | 40 Participants | 16 Participants |
| Sex: Female, Male Male | 11 Participants | 33 Participants | 22 Participants |
| Young Mania Rating Scale (YMRS) | 10.4 units on a scale STANDARD_DEVIATION 4.3 | 10.1 units on a scale STANDARD_DEVIATION 4.3 | 10.1 units on a scale STANDARD_DEVIATION 4.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 38 | 0 / 35 |
| serious Total, serious adverse events | 4 / 38 | 3 / 35 |
Outcome results
Primary
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.
Time frame: 12 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregnenolone | The 17-item Hamilton Rating Scale for Depression (HRSD17) | 9.18 units on a scale | Standard Error 1.41 |
| Placebo | The 17-item Hamilton Rating Scale for Depression (HRSD17) | 9.41 units on a scale | Standard Error 1.35 |
Comparison: Baseline HRSD scores used as covariate.p-value: 0.9084ANCOVA
Secondary
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.
Time frame: 12 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregnenolone | Hamilton Rating Scale for Anxiety (HRSA) | 8.80 units on a scale | Standard Error 1.63 |
| Placebo | Hamilton Rating Scale for Anxiety (HRSA) | 10.32 units on a scale | Standard Error 1.57 |
Comparison: Baseline HRSA used as a covariate.p-value: 0.511ANCOVA
Secondary
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
Time frame: 12 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregnenolone | Inventory of Depressive Symptomatology-Self Report (IDS-SR) | 15.78 units on a scale | Standard Error 2.64 |
| Placebo | Inventory of Depressive Symptomatology-Self Report (IDS-SR) | 18.23 units on a scale | Standard Error 2.54 |
Comparison: Baseline IDS-SR used as a covariate.p-value: 0.5187ANCOVA
Secondary
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
Time frame: 12 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregnenolone | Young Mania Rating Scale (YMRS) | 5.84 units on a scale | Standard Error 1.09 |
| Placebo | Young Mania Rating Scale (YMRS) | 6.63 units on a scale | Standard Error 1.05 |
Comparison: Baseline YMRS used as a covariate.p-value: 0.606ANOVA