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

Major Depressive Disorder Clinical Trial

Official title:

Treatment-Resistant Depression Augmentation Therapy With An Analog of the Neuroactive Steroid Allopregnanolone: A Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02900092
• Other study ID #: 2016P001182
• Status: Completed
• Phase: N/A
• Start date: November 2016
• Est. completion date: January 12, 2018

Study information

• Verified date: February 2019
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: January 12, 2018
• Est. primary completion date: January 12, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 50 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Depressive Disorder, Treatment-Resistant
• Major Depressive Disorder

Intervention

Drug:
• Ganaxolone
Participants received ganaxolone

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Montgomery-Asberg Depression Rating Scale (MADRS)	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).	Week 8