Home
Search
Study Topics
Glossary
|
|
|
|
|
Sponsored by: |
National Institute of Mental Health (NIMH) |
---|---|
Information provided by: | National Institutes of Health Clinical Center (CC) |
ClinicalTrials.gov Identifier: | NCT00738270 |
This study will examine the safety and effectiveness of an experimental drug called AZD2327 for treating anxious major depressive disorder. Studies in animals and humans have shown that the drug causes changes in certain body chemicals that may make it an effective antidepressant and antianxiety medication.
People 18 to 65 years of age who are diagnosed with anxious major depressive disorder without psychotic features may be eligible for this study.
Candidates are screened with a psychiatric and medical history, diagnostic interview, physical examination, electrocardiogram (ECG), electroencephalogram (EEG) and blood and urine tests.
Participants are tapered off any medications, including antidepressants, that are prohibited during the study and remain drug-free for 2 weeks. They are then randomly assigned to take the study medication or placebo and are hospitalized for 7 days for monitoring while taking the medication. They are then discharged from the hospital to continue the medication at home for 4 weeks, returning to the clinic once a week for evaluation of anxiety and depression, vital signs check and blood and urine tests. In addition, three EEGs are done during this period.
After the treatment period, subjects have a physical exam, ECG and blood tests. They receive short-term (up to 3 months) standard clinical treatment and are then transferred to the care of an outside clinician for long-term treatment.
In addition to the above procedures, subjects may participate in the following optional tests before starting treatment and at three other times during the study:
Condition | Intervention | Phase |
---|---|---|
Depression Anxiety Disorder |
Drug: AZD2327 |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study |
Official Title: | An Investigation of the Antidepressant Efficacy of a Selective, High Affinity Enkephalinergic Agonist in Anxious Major Depressive Disorder |
Estimated Enrollment: | 96 |
Study Start Date: | August 2008 |
There is increasing evidence that patients with anxious major depressive disorder (AMDD) have a greater depressive severity, functional impairment, increased risk of suicidality, worse social distress, higher incidence of alcohol and drug abuse, and poorer treatment response and outcome than patients with non-anxious depression. A recent report by STAR*D emphasizes the worse outcome of patients with this type of depression. The investigators found that remission was significantly less likely and to taker longer to occur in patients with anxious versus nonanxious depression. Current antidepressants are largely me too drugs in as much as they exert their primary biochemical effects by increasing the intrasynaptic levels of monoamines, and as such, there has been limited (if any) progress in developing medications with improved efficacy.
There is increasing literature of the involvement of the endogenous opioid system in major depression and its treatment. Identification of delta-opioid receptor as a possible target in the treatment of depression and anxiety began with clinical observations that a heightened anxiety state and depressive-like behaviors were consistently noted in the delta-opioid receptor knockout mouse. A number of investigators have found that selective delta-opioid receptor agonists have antidepressant-like properties in models such as the forced swim test. In a search for a selective delta-opioid receptor agonist to test in a proof-of-concept clinical study in AMDD, AZD2327 is a potent, first in class, high-affinity enkephalinergic agonist that possesses anxiolytic and antidepressant activity in animal models. AZD2327 has efficacy comparable to diazepam and imipramine in rodent models of anxiety and depression, respectively. Phase I studies have been completed and have indicated an acceptable safety profile.
In summary, clear preclinical signals for efficacy and an acceptable safety profile in Phase I studies to date have been seen with the enkephalinergic agonist AZD2327, suggesting that it might be a highly novel and effective therapy in both anxiety and depression. Furthermore, understanding the mechanism of action of enkephalinergic agonists' antidepressant effect may ultimately lead to further insight into the pathophysiology of mood disorders in general.
Male and female patients, ages 18 to 65, with a diagnosis of major depression (without psychotic features) meeting criteria for AMDD, will be randomized to double-blind treatment to receive either AZD2327 (3 mg BID) or placebo in a 2:1 ratio for a period of 4 weeks. In addition, a series of surrogate neurobiological markers will be obtained to establish whether they are capable of predicting therapeutic response. Approximately 96 patients with acute major depression will be enrolled in the study.
Ages Eligible for Study: | 18 Years to 65 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
For inclusion in the study, patients must fulfill all of the following criteria:
296.22 Major Depressive Disorder, Single Episode, Moderate or
296.23 Major Depressive Disorder, Single Episode, Severe Without Psychotic Features, duration at least 1 year or
296.32, Major Depressive Disorder, Recurrent, Moderate or
296.33, Major Depressive Disorder, Recurrent, Severe Without Psychotic Features.
EXCLUSION CRITERIA:
Any of the following is regarded as a criterion for exclusion from the study:
Patients can be retested if the initial UDS is positive, but should be excluded if the results are still positive, at the second test. Patients with a positive UDS for a drug(s) legally available by prescription must provide evidence of the prescription for the drug(s).
Patients with a suicide or homicide attempt within the past 6 months.
carbamazepine, phenytoin, barbiturates, rifampin, rifabutin, glucocorticoids, thioridazine and St. John's Wort; e.g., inhibitors: ketoconazole (except for topical use), itraconazole, fluconazole, erythromycin, clarithromycin, fluoxetine, nefazodone, troleandomycin, indinavir, nelfinavir, ritonavir, and saquinavir.
Contact: Patient Recruitment and Public Liaison Office | (800) 411-1222 | prpl@mail.cc.nih.gov |
Contact: TTY | 1-866-411-1010 |
United States, Maryland | |
National Institutes of Health Clinical Center, 9000 Rockville Pike | Recruiting |
Bethesda, Maryland, United States, 20892 |
Responsible Party: | National Institutes of Health ( Carlos A. Zarate, M.D./National Institute of Mental Health ) |
Study ID Numbers: | 080196, 08-M-0196 |
Study First Received: | August 16, 2008 |
Last Updated: | April 29, 2009 |
ClinicalTrials.gov Identifier: | NCT00738270 History of Changes |
Health Authority: | United States: Federal Government |
Depression Enkephalinergic Mood Disorder |
Depression Anxiety Anxious Major Depressive Disorder |
Depression Anxiety Disorders Mental Disorders Mood Disorders |
Depressive Disorder, Major Depressive Disorder Antidepressive Agents Behavioral Symptoms |
Pathologic Processes Disease Depression Anxiety Disorders Mental Disorders |
Mood Disorders Depressive Disorder, Major Depressive Disorder Behavioral Symptoms |