Dopaminergic Effects of Adjunctive Aripiprazole on the Brain in Treatment-Resistant Depression

NCT00953745 | Completed Results

• 1 other identifier: 201101790-2
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

Aripiprazole has been approved by the FDA for augmenting ineffective/partially effective oral antidepressant therapy in patients suffering from major depression. The mechanism by which this augmentation is achieved is not known. This study has been designed to test the hypothesis that the primary mechanism of action of aripiprazole (ARP) antidepressant augmentation is through the dopaminergic pathway. Two positron emission tomography (PET) scan procedures and a functional magnetic resonance imaging (fMRI) scan will be used to test this hypothesis.

Conditions

Major Depressive Disorder

Keywords

Depression; Neuroimaging; Aripiprazole; Mood disorder; PET Scan; fMRI

Outcome Measures

Primary Outcomes (1)

• Fluorodopa Uptake Values in Brain Images of Aripiprazole Augmentation Responders

  A ratio of the image derived radioactivity concentration and the whole body concentration of the injected radioactivity specifically in a cluster within the right medial caudate (see data below).

  Week 10 and Week 16 (6 weeks of combined therapy)

Secondary Outcomes (1)

• Depression Symptom Change on The Montgomery-Åsberg Depression Rating (MADRS) Scale Between ARP Responders and Non-responders.

  Week 10 and Week 16 (6 weeks of combined therapy)

Study Arms (2)

Depressed Participants

ACTIVE COMPARATOR

Subjects with treatment-resistant depression (TRD) will be administered the Hamilton Depression Rating Scale (HAM-D 17) for entry and will receive escitalopram combined with an adjunctive placebo capsule for 8 weeks. Subjects who fail to respond will continue to receive escitalopram and additionally change to receive a placebo tablet resembling the active augmentation agent Aripiprazole (ARP) for 2 weeks. Subjects who fail to respond to escitalopram after the 2 phase placebo treatment will enter the ARP augmentation phase of the study and will receive escitalopram augmentation with ARP. Subjects will have 3 neuroimaging scans: F-DOPA PET, raclopride PET, and functional MRI conducted after 10 weeks of treatment and repeated after 6 weeks of ARP treatment.

Drug: Escitalopram; Drug: Aripiprazole; Drug: Placebo Capsule; Drug: Placebo Tablet

Control Participants

NO INTERVENTION

Non-depressed, age- and sex-matched subjects without a DSM-IV Axis I diagnosis will serve as controls. They will not receive antidepressant, ARP, or any drug augmentation and will be used as quality control to compare the pre-ARP and post-ARP treatment brain images.

Interventions

Escitalopram DRUG

All subjects will begin on escitalopram and placebo for 8 weeks

Also known as: Lexapro

Depressed Participants

Aripiprazole DRUG

Subjects who fail to respond to Escitalopram will continue on Escitalopram and augment with active Aripiprazole.

Also known as: Abilify

Depressed Participants

Placebo Capsule DRUG

All subjects will begin on escitalopram and placebo capsule for 8 weeks.

Depressed Participants

Placebo Tablet DRUG

After 8 weeks, subjects will be given a 2 week supply of escitalopram and placebo tablet.

Depressed Participants

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects with known history of MDD verified using the Mini International Neuropsychiatric Interview and a Hamilton Depression Rating Scale 17-item score of at least 18
• Subjects must have failed to respond to one previous adequate dose-duration trial of antidepressant therapy
• Must complete the MRI screening tool and demonstrate ability to receive an MRI
• For entry into the ARP augmentation phase the subject must be a non-responder to the escitalopram phase as demonstrated by a MADRS score at week 10, that is not reduced by greater than 50% from baseline.

You may not qualify if:

• Subjects cannot be smokers
• No significant history of anxiety disorder
• Cannot be pregnant or lactating and sexually active women of childbearing potential must use a medically accepted means of contraception
• The following DSM-IV diagnoses are excluded: Organic mental disorder; substance abuse/dependence, including alcohol, active within the last year; schizophrenia, paranoid or delusional disorders; other psychotic disorders; panic disorder; generalized anxiety disorder; obsessive-compulsive disorder, or post-traumatic stress disorder; bipolar disorder; bulimia nervosa; anorexia nervosa
• Subjects with serious suicidal risks
• Subjects who have taken any antidepressant medication other than escitalopram within 5 half lives, of the most recent antidepressant taken
• Subjects involved in any other form of treatment for depression
• Subjects who have demonstrated any previous inadequate antidepressant response to electroconvulsive therapy (ECT)
• Subjects who have received ECT for the current depression episode
• Subjects who have been hospitalized within 4 weeks of the study
• Subjects who have received treatment with a monoaminoxidase inhibitor within 2 weeks of enrollment
• Subjects with a known allergy, hypersensitivity, or previous unresponsiveness to aripiprazole or known intolerance to any study medications
• Subjects with a history of participation in any investigational medication trial in the past month
• A positive drug screen or substance use disorder in the past 12 months
• History of any thyroid pathology

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Washington University in St. Louis, School of Medicine

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Depression; Mood Disorders

Interventions

Escitalopram; Aripiprazole

Condition Hierarchy (Ancestors)

Depressive Disorder; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Quinolones; Quinolines

Results Point of Contact

• Title: Dr. Charles R. Conway, MD
• Organization: Washington University School of Medicine

conwayc@psychiatry.wustl.edu

314-362-7566

Study Officials

• Charles R Conway, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is designed to help understand the mechanism of action of aripiprazole in MDD augmentation. Subjects will undergo exposure to en an existing antidepressant (Lexapro 10-20mg) for 10 weeks; subjects failing to completely respond to the monotherapy antidepressant treatment will receive augmentation with aripiprazole for six weeks. We have included two placebo phases to the study in which the subjects received one placebo along with the Lexapro for the first 6 weeks and a second placebo along with Lexapro for the next two weeks (weeks 7 and 8). This double placebo design is to ensure that subjects receiving aripiprazole augmentation have a legitimate response (non-placebo) to the aripiprazole augmentation. Since the N of this study is small and a small % of patients with placebo response could skew the imaging data significantly, the use of a double placebo prior to the start of the true aripiprazole augmentation should reduce or eliminate a placebo response.

Study Record Dates

• First Submitted: August 4, 2009
• First Posted: August 6, 2009
• Study Start: May 1, 2009
• Primary Completion: June 1, 2012
• Study Completion: December 1, 2012
• Last Updated: April 19, 2018
• Results First Posted: April 19, 2018

Record last verified: 2018-04

Locations

US (1)