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A 12-Week, Placebo Controlled Trial of Ziprasidone as Monotherapy for Major Depressive Disorder (Geodon)

This study has been completed.
Sponsor:
Collaborators:
Cambridge Health Alliance
University of Connecticut
Vanderbilt University
Psychiatric Medicine Associates, L.L.C.
Cedars-Sinai Medical Center
Information provided by (Responsible Party):
George I. Papakostas, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00555997
First received: November 7, 2007
Last updated: June 23, 2014
Last verified: June 2014
  Purpose

This is a study on the effectiveness, tolerability and safety of oral ziprasidone as monotherapy in patients with major depressive disorder (MDD). Outpatients suffering from MDD will be treated with either ziprasidone or placebo for 12 weeks.

Hypothesis: There will be a statistically significant difference in the magnitude of response, as measured by a decrease in baseline 17-item Hamilton Depression Rating Scale (HAM-D-17) scores, between the two treatment groups; the reduction in HAM-D-17 scores will be greater in the ziprasidone monotherapy group than in the placebo group.


Condition Intervention Phase
Major Depressive Disorder
Drug: Ziprasidone
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 12-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel-Sequential Trial of Ziprasidone as Monotherapy for Major Depressive Disorder

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Hamilton Depression Rating Scale (HAM-D-17) Scores [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Higher numbers represent more symptoms of a major depressive episode. Minimum is 0. Maximum is 52.


Secondary Outcome Measures:
  • Responder/Non-responder [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    A responder during phase 1 or phase 2 is someone who demonstrated a 50% or greater decrease in HAMD-17 scores during phase 1 or phase 2 (corresponding).

  • Change in 6-VAS-D Scores During Each Phase. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Enrollment: 120
Study Start Date: March 2008
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Patients in group 1 will receive Ziprasidone for the full 12 weeks of the study.
Drug: Ziprasidone
20mg-80mg a day. Dose increases of 20mg per day may occur at three study visits as directed by clinician. Maximum; 80mg per day per patient.
Other Name: Geodon
Active Comparator: 2
Patients in Group 2 will receive placebo for the first 6 weeks of the study, then will receive Ziprasidone for the last 6 weeks.
Drug: Ziprasidone
20mg-80mg a day. Dose increases of 20mg per day may occur at three study visits as directed by clinician. Maximum; 80mg per day per patient.
Other Name: Geodon
Placebo Comparator: 3
Patients in Group 3 will receive placebo for the full 12 weeks of the study.
Drug: Placebo
0mg Placebo per day. "Dose increases" and "dose decreases" may occur, but patient will remain at 0mg placebo

Detailed Description:

Exploratory hypothesis 1: There will be a statistically significant difference in the percentage of responders in the two treatment groups; response rates will be significantly higher for the ziprasidone monotherapy compared to the placebo group.

Exploratory hypothesis 2: The change in 6-VAS-D scores during the trial will be highly correlated to the change in HAM-D-17 and QIDS-SR during the trial.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 18-65.
  2. Written informed consent.
  3. MDD, current according to the fourth version of the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV) as diagnosed by the Mini International Neuropsychiatric Interview (MINI; Sheehan et al, 1998).
  4. Quick Inventory of Depressive Symptomatology - Self-Rated (QIDS-SR- Trivedi et al, 2004) score of at least 10 at both screen and baseline visits.

Exclusion Criteria:

  1. Pregnant women.
  2. Women of child bearing potential who are not using a medically accepted means of contraception (to include oral contraceptive or implant, condom, diaphragm, spermicide, intrauterine device, tubal ligation, or a partner with vasectomy).
  3. Treatment with antidepressants for 2 weeks prior to the screen visit. If interested in discontinuing their current medication, potential participants must discuss this possibility with the prescribing physician. Study doctors will not implement any form of treatment washout.
  4. Patients who no longer meet DSM-IV criteria for MDD during the baseline visit, or patients who demonstrate a 25% or greater reduction in QIDS-SR scores, screening to baseline.
  5. Serious suicide or homicide risk, as assessed by the evaluating clinician or a score of 4 on the third item of the HAM-D.
  6. Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease.
  7. Patients who meet criteria for alcohol or substance dependence, active within the last month.
  8. Any bipolar disorder (current or past).
  9. Any psychotic disorder (current or past).
  10. Psychotic features in the current episode or a history of psychotic features.
  11. History of a seizure disorder.
  12. Clinical or laboratory evidence of untreated hypothyroidism.
  13. Patients requiring excluded medications (see table 1 for details).
  14. Prior course of ziprasidone, or intolerance to ziprasidone at any dose.
  15. Any investigational psychotropic drug within the last 3 months.
  16. Patients with significant cardiac conduction problems on screening electrocardiogram such as atrial fibrillation, atrial flutter, atrio-ventricular block, prolonged or abnormal QTc interval (i.e. QTc>450msec), or prolonged QRS interval.
  17. Patients who have suffered a myocardial infarction within the past 12 months, with uncompensated heart failure, or a history of QTc prolongation.
  18. Patients with abnormal serum potassium or magnesium levels upon screening.
  19. Patients currently taking other drugs that prolong the QTc including dofetilide, sotalol, quinidine, class Ia antiarrhythmics, class III antiarrhythmics, mesoridazine, thioridazine, chlorpromazine, droperidol, pimozide, sparfloxacin, gatifloxacin, moxifloxacin, halofantrine, mefloquine, pentamidine, arsenic trioxide, levomethadyl acetate, dolasetron methylate, probucol or tacrolimus.
  20. Patients who have failed to experience significant clinical improvement following 3 or more antidepressant trials of adequate duration (at least 6 weeks) and dose (minimal effective doses defined as: fluoxetine, paroxetine, citalopram 20mg; sertraline, fluvoxamine 50mg, escitalopram 10mg, paroxetine CR 25mg, venlafaxine 75mg, duloxetine 60mg, bupropion 150mg, 15mg of mirtazapine, trazodone or nefazodone 300mg).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00555997

Locations
United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
United States, Connecticut
University of Connecticut Health Center
Farmington, Connecticut, United States, 06030-6415
Comprehensive Psychiatric Care
Norwich, Connecticut, United States, 06360
United States, Illinois
Psychiatric Medicine Associates, L.L.C.
Chicago, Illinois, United States, 60612
United States, Massachusetts
Massachusetts General Hosptial
Boston, Massachusetts, United States, 02114
Cambridge Health Alliance
Cambridge, Massachusetts, United States, 02139
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37212
Sponsors and Collaborators
Massachusetts General Hospital
Cambridge Health Alliance
University of Connecticut
Vanderbilt University
Psychiatric Medicine Associates, L.L.C.
Cedars-Sinai Medical Center
Investigators
Principal Investigator: George I Papakostas, M.D. Massachusetts General Hospital
Principal Investigator: John M Zajecka, M.D. Psychiatric Medicine Associates, L.L.C.
Principal Investigator: Richard C Shelton, M.D. Vanderbilt University
Principal Investigator: Andrew Winokur, M.D. University of Connecticut Health Center
Principal Investigator: Gustavo Kinrys, M.D. Cambridge Health Alliance
Principal Investigator: Waguih IsHak, M.D. Cedar's Sinai
Principal Investigator: Mahmoud S Okasha, MD Comprehensive Psychiatric Care, Norwich CT
  More Information

Additional Information:
Publications:
Responsible Party: George I. Papakostas, Director of Treatment-Resistant Studies, Depression Clinical and Research Program, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00555997     History of Changes
Other Study ID Numbers: 2007-P-000623
Study First Received: November 7, 2007
Results First Received: July 9, 2013
Last Updated: June 23, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Major Depressive Disorder
Major Depression
Depression
Geodon
Ziprasidone

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Disease
Behavioral Symptoms
Mental Disorders
Mood Disorders
Pathologic Processes
Ziprasidone
Antipsychotic Agents
Central Nervous System Agents
Central Nervous System Depressants
Dopamine Agents
Dopamine Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Antagonists
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on November 27, 2014