Org 24448 to Treat Major Depression

Phase 2

Terminated

Conditions: Depression

Interventions: Drug: Org 24448
Drug: Placebo

Registration Number: NCT00113022

Lead Sponsor: National Institute of Mental Health (NIMH)

Brief Summary: This study will evaluate the effectiveness of the experimental drug, Org 24448, for short-term treatment of depression. It will examine the effects of the drug on symptoms, such as low mood and persistent sadness, poor sleep and appetite, poor motivation and lack of enjoyment of things people normally enjoy, negative thinking, and feeling slowed down or having trouble concentrating. It will also assess whether the drug improves cognitive function, especially memory.

Patient with major depression who do not have a serious, unstable medical illness and who are 21 to 55 years of age may be eligible for this study. Candidates are screened with a psychiatric and medical history, diagnostic interview, physical examination, electrocardiogram, blood tests and, for women, a pregnancy test.

Participants are tapered off anti-depression drugs (and any other medications not allowed on the study) over a 3-week period and then begin a 2-week drug-free period. During these 2 weeks they have an electroencephalogram (EEG) with light stimulation, and those whose EEG indicates a seizure disorder are excluded from the study. Also at the beginning of the drug-free period they begin taking a placebo ("sugar pill") twice a day. After 2 weeks on placebo, some patients begin treatment with Org 24448, while others remain on placebo. They continue the medication for 8 weeks, during which time they have a weekly check of vital signs, blood and urine tests, and rating scales for depression and anxiety. Level of functioning is evaluated twice during the study. After 8 weeks of treatment, patients have a physical exam, electrocardiogram (ECG), EEG, blood tests, and begin to come off the study drug, tapering the medication over a week.

In addition to the above procedures, some patients undergo the following tests during the 2-week drug-free period and again toward the end of the 8-week medication phase:

* Neuropsychological testing, including measurements of cognitive abilities such as memory, attention, problem-solving, and language skills.

* Positron emission tomography (PET): This nuclear medicine test provides information about different brain regions. The patient lies on a table in the PET scanner (similar to a computed tomography (CT) scanner), with a mask placed over his or her face that helps keep the head still. A sugar fluid with a radioactive material attached to it is injected into a catheter (plastic tube) that has been inserted into a vein in the patient's arm. The scanner detects ...

Detailed Description: Depression is a devastating illness that is estimated to affect 12% to 17% of the population at some point during the lifetime of an individual. Despite the availability of a wide range of antidepressant drugs, 30% to 40% of patients with major depression fail to respond to first-line antidepressant (e.g., selective serotonin reuptake inhibitors (SSRIs)) treatment, despite adequate dosage, duration, and compliance. Thus there is a clear need to develop novel and improved therapeutics for major depression. Current pathophysiological theories regarding the neurobiology of depression include alterations in intracellular signaling cascades, and impairments of cellular plasticity and resilience. There is recent evidence suggesting that promoting growth factors such as brain derived neurotrophic factor (BDNF) may provide a mechanism for the treatment of depression. New information indicating modulation of glutamate receptors in the actions of antidepressant treatments suggests a novel approach to develop a new class of antidepressants. Studies have shown that the biarylpropylsulfonamide AMPA (2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid) receptor potentiators (LY392098 and LY451616) have antidepressant effects in animal models of depression. Several studies have demonstrated that AMPA receptor activation can increase expression of BDNF both in vitro and in vivo. Thus, one possible new approach for the treatment of depression is to use an AMPA receptor potentiator.

In this study we propose to compare the ampakine receptor potentiator Org 24448 to placebo for the treatment of Major Depression. Inpatients and outpatients (primarily outpatients), ages 21 to 70, with a diagnosis of Major Depression (without psychotic features), will be randomized to double-blind treatment to either Org 24448 or placebo for a period of 8 weeks. Acute efficacy will be determined by demonstrating a greater response rate using specified criteria. Approximately 90 patients with acute major depression will be enrolled in the study in order to reach the goal of randomizing 70 patients in the controlled trial.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 9

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Org 24448	Org 24448	Blinded, active experimental compound
Placebo	Placebo	Blinded placebo

Primary Outcome Measures

Name	Time	Method
Montgomery-Asberg Depression Rating Scale (MADRS)	8 weeks	The MADRS is a measure of depression severity examined on a weekly basis. The minimum score on the 10 item scale is 0 indicating no depression. The maximum score is 60 indicating a very severe depression. Scores of 18 and above are generally considered to suggest significant levels of depression.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (2): National Institutes of Health Clinical Center, 9000 Rockville Pike
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Bethesda, Maryland, United States
Mt. Sinai Medical Center
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New York, New York, United States