Augmentation of Treatment-Resistant Depression With An Analog of the Neuroactive Steroid Allopregnanolone

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02900092
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arm: 1
• Actual Duration (Months): 14.4
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

Major depressive disorder (MDD) is highly prevalent and nearly 70% of individuals with MDD do not respond to standard antidepressant therapies despite adequate dosing. An effective and well-tolerated antidepressant augmentation therapy would have important clinical and public health implications. Neuroactive steroid hormones are known to directly activate neurotransmitter receptors in the brain, and thus are potential candidates for augmentation therapies to enhance the effect of traditional antidepressants. The investigators hypothesize that administration of an allopregnanolone analog in women with treatment-resistant depression will improve depressive symptoms.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Ganaxolone	N/A

Detailed Description

Major depressive disorder (MDD) is highly prevalent and can have profoundly negative consequences on one's health, well-being and productivity. Women are twice as likely as men to experience depression during their lifetimes. In fact, it is reported that twelve million women in the U.S. each year will experience depression, and that one in eight women will experience a clinical depressive episode during their lifetimes. Additionally, nearly 70% of individuals with MDD do not respond to standard antidepressant therapies despite adequate dosing. Therefore, the identification of an effective and well tolerated antidepressant augmentation therapy would have important clinical and public health implications. Neuroactive steroid hormones are known to directly activate neurotransmitter receptors in the brain, and thus are potential candidates for augmentation therapies to enhance the effect of traditional antidepressants. Specifically, allopregnanolone, a steroid hormone derived from progesterone, is a potent positive modulator of GABA action at GABA-A receptors, which are known to have positive effects on mood symptoms. Data suggest that depression, chronic stress and posttraumatic stress disorder may be associated with low central nervous system allopregnanolone levels. The investigators propose to administer an oral allopregnanolone analog to 10 postmenopausal women with treatment-resistant depression as an add-on therapy to their current treatment for a period of 8 weeks followed by a 2-week taper. The investigators hypothesize that administration of the oral allopregnanolone analog in women with treatment-resistant depression will improve depressive symptoms.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Treatment-Resistant Depression Augmentation Therapy With An Analog of the Neuroactive Steroid Allopregnanolone: A Pilot Study
• Actual Study Start Date: Nov 1, 2016
• Actual Primary Completion Date: Jan 12, 2018
• Actual Study Completion Date: Jan 12, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ganaxolone Participants received ganaxolone	Drug: Ganaxolone; Participants received ganaxolone

Outcome Measures

Primary Outcome Measures

1. Montgomery-Asberg Depression Rating Scale (MADRS) [Week 8]

   The MADRS is a diagnostic questionnaire that is used to measure the severity of depressive episodes in patients with mood disorders. The minimum and maximum values are 0 and 60, respectively, (higher scores are more severe).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 75 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Female, age 50-75

2. Postmenopausal

3. Major Depressive Disorder

4. Currently treated with SSRI or SNRI at adequate dose

Exclusion Criteria:

1. Serious suicide or homicide risk

2. Unstable medical illness

3. Substance use disorder

4. Psychosis

5. Use of hormones (estrogens, androgens or related hormones)

6. History of hormone responsive cancer

7. Receiving strong CYP3A4 inducers or inhibitors or who intend to consume grapefruit products regularly during the study

8. Alanine aminotransferase (ALT) or creatinine > 3x upper limit of normal

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital

Investigators

• Principal Investigator: Karen K Miller, MD, Massachusetts General Hospital

Study Documents (Full-Text)

• Study Protocol - May 14, 2018
• Statistical Analysis Plan - Nov 8, 2018

More Information

Publications

None provided.

• Responsible Party: Karen Klahr Miller, MD, Professor of Medicine, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT02900092
• Other Study ID Numbers: 2016P001182
• First Posted: Sep 14, 2016
• Last Update Posted: Feb 18, 2019
• Last Verified: Feb 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Karen Klahr Miller, MD, Professor of Medicine, Massachusetts General Hospital: postmenopausal; women; depression
• Additional relevant MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Ganaxolone

Study Results

Participant Flow

Arm/Group Title	Ganaxolone Treatment Arm
Arm/Group Description	Participants randomized to ganaxolone treatment
Period Title: Overall Study
STARTED	10
COMPLETED	9
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Ganaxolone Treatment Arm
Arm/Group Description	Participants received ganaxolone
Overall Participants	10
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.8 (6.3)
Sex: Female, Male (Count of Participants)
Female	10 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	10 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	10 100%
Montgomery-Asberg Depression Rating Scale (MADRS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	24.4 (5.1)

Outcome Measures

1. Primary Outcome

Title	Montgomery-Asberg Depression Rating Scale (MADRS)
Description	The MADRS is a diagnostic questionnaire that is used to measure the severity of depressive episodes in patients with mood disorders. The minimum and maximum values are 0 and 60, respectively, (higher scores are more severe).
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

Ten subjects started the study. One subject dropped out (did not complete the 8-week study). Therefore, data from 9 subjects were analyzed.

Arm/Group Title	Ganaxolone Treatment Arm
Arm/Group Description	Participants received ganaxolone
Measure Participants	9
Mean (Standard Deviation) [units on a scale]	12.8 (2.9)

Adverse Events

Time Frame	8 weeks
Arm/Group Title	Ganaxolone Treatment Arm
Arm/Group Description	Participants received ganaxolone treatment
All Cause Mortality
	Ganaxolone Treatment Arm
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Serious Adverse Events
	Ganaxolone Treatment Arm
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Other (Not Including Serious) Adverse Events
	Ganaxolone Treatment Arm
	Affected / at Risk (%)	# Events
Total	10/10 (100%)
General disorders
Sleepiness and fatigue	10/10 (100%)
Dizziness	6/10 (60%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.