Study Using Pregnenolone to Treat Bipolar Depression

• Sponsor: University of Texas Southwestern Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01409096
• Collaborator: Stanley Medical Research Institute (Other)
• Enrollment: 80
• Location: 1
• Arms: 2
• Duration (Months): 20
• Patients Per Site Per Month: 4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder; Major Depressive Disorder	Drug: Pregnenolone; Drug: Placebo	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double Blind, Placebo-controlled Trial of Pregnenolone for Bipolar Depression
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Nov 1, 2011
• Actual Study Completion Date: Nov 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	Drug: Pregnenolone; Pregnenolone is a naturally occurring neurosteroid that is synthesized from cholesterol in the adrenal glands and central nervous system.; Other Names: 3β-hydroxypregn-5-en-20-one
Placebo Comparator: Placebo The arm will be given placebo that matches the Pregnenolone at the same frequency as the Pregnenolone for 12 weeks.	Drug: Placebo; Inactive ingredient matching the active medication in appearance.; Other Names: Sugar pill

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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

2. 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

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Texas Southwestern Medical Center	Dallas	Texas	United States	75235

Sponsors and Collaborators

• University of Texas Southwestern Medical Center
• Stanley Medical Research Institute

Investigators

• Principal Investigator: Edson S Brown, MD/PhD, UT Southwestern Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sherwood Brown, Principal Investigator, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT01409096
• Other Study ID Numbers: 122009-069
• First Posted: Aug 3, 2011
• Last Update Posted: Mar 31, 2016
• Last Verified: Mar 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Additional relevant MeSH terms: Disease; Depressive Disorder; Depressive Disorder, Major; Bipolar Disorder

Study Results

Participant Flow

Arm/Group Title	Pregnenolone	Placebo
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	40	40
COMPLETED	38	35
NOT COMPLETED	2	5

Baseline Characteristics

Arm/Group Title	Pregnenolone	Placebo	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	38	35	73
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.2 (8.5)	44.1 (10.4)	43.6 (9.5)
Sex: Female, Male (Count of Participants)
Female	16 42.1%	24 68.6%	40 54.8%
Male	22 57.9%	11 31.4%	33 45.2%
Race/Ethnicity, Customized (participants) [Number]
African-American	18 47.4%	15 42.9%	33 45.2%
Caucasian	18 47.4%	16 45.7%	34 46.6%
Hispanic	2 5.3%	4 11.4%	6 8.2%
Bipolar Diagnosis (participants) [Number]
Bipolar I	16 42.1%	15 42.9%	31 42.5%
Bipolar II	21 55.3%	17 48.6%	38 52.1%
Bipolar Not Otherwise Specified	1 2.6%	3 8.6%	4 5.5%
Age of onset of mood symptoms (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26.4 (9.0)	26.7 (7.3)	26.7 (8.22)
Concomitant Medications: Lithium (participants) [Number]
Lithium	5 13.2%	4 11.4%	9 12.3%
No Lithium	33 86.8%	31 88.6%	64 87.7%
Concomitant Medications: Anticonvulsant (participants) [Number]
Anticonvulsants	10 26.3%	10 28.6%	20 27.4%
No anticonvulsants	28 73.7%	25 71.4%	53 72.6%
Concomitant Medications: Antidepressant (participants) [Number]
Antidepressants	21 55.3%	22 62.9%	43 58.9%
No antidepressants	17 44.7%	13 37.1%	30 41.1%
Concomitant Medications: Antipsychotic (participants) [Number]
Antipsychotic	17 44.7%	18 51.4%	35 47.9%
No antipsychotic	21 55.3%	17 48.6%	38 52.1%
Concomitant Medications: Sedative/hypnotic/anxiolytic (participants) [Number]
Sedative/hypnotic/anxiolytic	16 42.1%	20 57.1%	36 49.3%
No Sedative/hypnotic/anxiolytic	22 57.9%	15 42.9%	37 50.7%
Concomitant medications: Stimulant (participants) [Number]
Stimulant	0 0%	1 2.9%	1 1.4%
No stimulant	38 100%	34 97.1%	72 98.6%
Concomitant medications: None (participants) [Number]
No concomitant medications	7 18.4%	6 17.1%	13 17.8%
Concomitant medication	31 81.6%	29 82.9%	60 82.2%
Hamilton Rating Scale for Depression (HRSD) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	21.3 (4.0)	23.5 (4.6)	22.4 (4.3)
Inventory of Depressive Symtomatology-Self Report (IDS-SR) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	38.0 (14.5)	47.5 (14.5)	42.7 (15.2)
Young Mania Rating Scale (YMRS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	10.1 (4.7)	10.4 (4.3)	10.1 (4.3)
Hamilton Rating Scale for Anxiety (HRSA) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	19.4 (9.8)	22.8 (8.1)	21.1 (9.2)

Outcome Measures

1. Primary Outcome

Title	The 17-item Hamilton Rating Scale for Depression (HRSD17)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pregnenolone	Placebo
Arm/Group Description	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.	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.
Measure Participants	38	35
Least Squares Mean (Standard Error) [units on a scale]	9.18 (1.41)	9.41 (1.35)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregnenolone, Placebo
	Comments	Baseline HRSD scores used as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9084
	Comments
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	Inventory of Depressive Symptomatology-Self Report (IDS-SR)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pregnenolone	Placebo
Arm/Group Description	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.	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.
Measure Participants	38	35
Least Squares Mean (Standard Error) [units on a scale]	15.78 (2.64)	18.23 (2.54)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregnenolone, Placebo
	Comments	Baseline IDS-SR used as a covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5187
	Comments
	Method	ANCOVA
	Comments

3. Secondary Outcome

Title	Young Mania Rating Scale (YMRS)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pregnenolone	Placebo
Arm/Group Description	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.	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.
Measure Participants	38	35
Least Squares Mean (Standard Error) [units on a scale]	5.84 (1.09)	6.63 (1.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregnenolone, Placebo
	Comments	Baseline YMRS used as a covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6060
	Comments
	Method	ANOVA
	Comments

4. Secondary Outcome

Title	Hamilton Rating Scale for Anxiety (HRSA)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pregnenolone	Placebo
Arm/Group Description	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.	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.
Measure Participants	38	35
Least Squares Mean (Standard Error) [units on a scale]	8.80 (1.63)	10.32 (1.57)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pregnenolone, Placebo
	Comments	Baseline HRSA used as a covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5110
	Comments
	Method	ANCOVA
	Comments

Adverse Events

Arm/Group Title	Pregnenolone		Placebo
Arm/Group Description	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.		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.
All Cause Mortality
	Pregnenolone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Pregnenolone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/38 (10.5%)		3/35 (8.6%)
Eye disorders
Corneal ulceration	1/38 (2.6%)	1	0/35 (0%)	0
Hepatobiliary disorders
Cholecystitis	0/38 (0%)	0	1/35 (2.9%)	1
Injury, poisoning and procedural complications
Injuries secondary to motor vehicle accident	0/38 (0%)	0	1/35 (2.9%)	1
Fall	0/38 (0%)	0	1/35 (2.9%)	1
Respiratory, thoracic and mediastinal disorders
Sinusitis	1/38 (2.6%)	1	0/35 (0%)	0
Skin and subcutaneous tissue disorders
Skin abscess followed by allergic reaction to antibiotic used to treat it	1/38 (2.6%)	1	0/35 (0%)	0
Skin rash	1/38 (2.6%)	1	0/35 (0%)	0
Other (Not Including Serious) Adverse Events
	Pregnenolone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/35 (0%)

Limitations/Caveats

Sample size; treatment groups not well matched on gender or depressive symptom scores

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.