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

February 13, 2019 updated by: Karen Klahr Miller, MD, Massachusetts General Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

10

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ganaxolone
Participants received ganaxolone
Drug: Ganaxolone
Participants received ganaxolone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Montgomery-Asberg Depression Rating Scale (MADRS)
Time Frame: 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).
Week 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2016

Primary Completion (Actual)

January 12, 2018

Study Completion (Actual)

January 12, 2018

Study Registration Dates

First Submitted

September 9, 2016

First Submitted That Met QC Criteria

September 9, 2016

First Posted (Estimate)

September 14, 2016

Study Record Updates

Last Update Posted (Actual)

February 18, 2019

Last Update Submitted That Met QC Criteria

February 13, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016P001182

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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