Org 24448 to Treat Major Depression

NCT00113022 | Terminated Phase 2 Results DMC

• 2 other identifiers: 05016105-M-0161
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

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 ...

Conditions

Depression

Keywords

Depression; Glutamate; Ampakine; Treatment; Memory; Major Depressive Disorder; AMPA Receptor Activation; BDNF

Outcome Measures

Primary Outcomes (1)

• Montgomery-Asberg Depression Rating Scale (MADRS)

  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.

  8 weeks

Study Arms (2)

Org 24448

EXPERIMENTAL

Blinded, active experimental compound

Drug: Org 24448

Placebo

PLACEBO COMPARATOR

Blinded placebo

Drug: Placebo

Interventions

Org 24448 DRUG

250 mg once per day for first week, 250 mg twice per day for second week, 500 mg twice per day for third and fourth weeks, if response minimal or worse at four weeks then 750 mg twice per day for additional weeks

Also known as: Ampakine

Org 24448

Placebo DRUG

Inactive equivalent of 250 mg once per day for first week, 250 mg twice per day for second week, 500 mg twice per day for third and fourth weeks, if response minimal or worse at four weeks then 750 mg twice per day for additional weeks

Placebo

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects, 21 to 70 years of age.
• Female subjects who are not of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year) or must be using a medically accepted means of contraception. Women using oral contraceptive medication for birth control must also be using a barrier contraceptive. Women of childbearing potential must also have a negative serum Beta-HCG (human chorionic gonadotropin) at pre-study.
• Subjects must fulfill DSM-IV criteria for Major Depression (296.3) without psychotic features, based on clinical assessment and confirmed by a structured diagnostic interview, the Structured Clinical Interview for DSM-IV TR Axis I Disorders, SCID-P.
• Subjects have a history of at least one previous episode of depression prior to the current episode.
• Subjects must have an initial score of greater than or equal to 32 on the Inventory of Depressive Symptoms, Clinician version (IDS-C) at Visit 1 and Visit 2.
• Subjects must not have greater than a 25% decrease in the IDS-C total scores during washout (between Visits 1 and 2).
• Each subject must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document.
• Current major depressive episode of at least 4 weeks duration.

You may not qualify if:

• Presence of psychotic features or a diagnosis of Schizophrenia or any other psychotic disorder or bipolar disorder as defined in the Diagnostic and Statistical Manual, Version IV (DSM-IV).
• Subjects with a diagnosis of Obsessive Compulsive Disorder as defined in the DSM-IV.
• Subjects with a history of DSM-IV drug or alcohol dependency or abuse (except for nicotine or caffeine) within the preceding 3 months.
• Female subjects who are either pregnant or nursing.
• Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
• Subjects with a history of neutropenia or medication-induced blood dyscrasia.
• Clinically significant abnormal findings of laboratory parameters, physical examination, EEG, or ECG.
• Subjects with a lifetime history of autism, mental retardation, pervasive developmental disorders, or Tourette's syndrome.
• Subjects with uncorrected hypothyroidism or hyperthyroidism.
• Subjects with one or more seizures without a clear and resolved etiology.
• Treatment with a reversible monoamine oxidase inhibitor (MAOI) within 2 weeks prior to Visit 2.
• Treatment with fluoxetine within 4 weeks prior to Visit 2.
• Treatment with clozapine or electroconvulsive therapy (ECT) within 3 months prior to study Visit 2.
• Judged clinically to be at serious suicidal or homicidal risk.
• Participation in a clinical trial of another investigational drug within 1 month prior to study entry (visit 1).

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (2)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Mt. Sinai Medical Center

New York, New York, 10029-0574, United States

Location

Related Publications (3)

• Anand A, Charney DS, Oren DA, Berman RM, Hu XS, Cappiello A, Krystal JH. Attenuation of the neuropsychiatric effects of ketamine with lamotrigine: support for hyperglutamatergic effects of N-methyl-D-aspartate receptor antagonists. Arch Gen Psychiatry. 2000 Mar;57(3):270-6. doi: 10.1001/archpsyc.57.3.270.

  PMID: 10711913 BACKGROUND

• Austin MP, Mitchell P, Goodwin GM. Cognitive deficits in depression: possible implications for functional neuropathology. Br J Psychiatry. 2001 Mar;178:200-6. doi: 10.1192/bjp.178.3.200.

  PMID: 11230029 BACKGROUND

• Austin MP, Mitchell P, Wilhelm K, Parker G, Hickie I, Brodaty H, Chan J, Eyers K, Milic M, Hadzi-Pavlovic D. Cognitive function in depression: a distinct pattern of frontal impairment in melancholia? Psychol Med. 1999 Jan;29(1):73-85. doi: 10.1017/s0033291798007788.

  PMID: 10077295 BACKGROUND

MeSH Terms

Conditions

Depression; Depressive Disorder, Major

Interventions

1-(benzofurazan-5-ylcarbonyl)piperidine

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Depressive Disorder; Mood Disorders; Mental Disorders

Results Point of Contact

• Title: Dr. Carlos Zarate
• Organization: Experimental Therapeutics and Pathophysiology Branch, NIMH

zaratec@mail.nih.gov

301-451-0861

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: June 2, 2005
• First Posted: June 3, 2005
• Study Start: May 1, 2005
• Primary Completion: February 1, 2007
• Study Completion: February 1, 2007
• Last Updated: July 13, 2012
• Results First Posted: July 6, 2012

Record last verified: 2012-07

Locations

US (2)