Major Depressive DisorderPhase 2NCT00633399
Ziprasidone Augmentation of SSRIs for Patients With Major Depressive Disorder (MDD) That do Not Sufficiently Respond to Treatment With SSRIs
A Phase 2 study testing Ziprasidone in people with Major Depressive Disorder, run by Massachusetts General Hospital at 2 sites in United States.
Trial summary
The purpose of this study is to see if adding the study drug, ziprasidone, to an antidepressant medication helps improve symptoms of Major Depressive Disorder (MDD). We are studying the drug's effectiveness in treating depression, as well as its safety when it is added to another drug. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Ziprasidone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 458 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2008to Mar 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent.
- Men or women, 18-65 years of age.
- MDD, current, according to DSM-IV criteria and as diagnosed by the SCID- I/P during the screen and baseline visit of phase 1.
- A HAM-D-17 score > 14 during the screen and baseline visit of phase 1.
Who cannot join
- Pregnant women or women of child bearing potential who are not using a medically accepted means of contraception (oral contraceptive or implant, condom, diaphragm, spermicide, intrauterine
- Device, tubal ligation, or partner with vasectomy).
- Serious suicide or homicide risk, as assessed by evaluating clinician.
- Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease or uncontrolled seizure disorder.
- History of multiple adverse drug reactions or allergy to the study drug.
- The following DSM-IV diagnoses: substance use disorders active within the last six months, any bipolar disorder (current or past), any psychotic disorder (current or past).
Show all 11Show fewer
- Patients requiring excluded medications (see appendix 1 for details).
- Psychotic features in the current episode or a history of psychotic features.
- Prior course of ziprasidone, or intolerance to ziprasidone at any dose.
- Any investigational psychotropic drug within the last 3 months.
- Have failed more than 3 adequate antidepressant trials during the current MDE. Some examples of adequate dosage of an antidepressant trial include either > 150 mg of imipramine (or its tricyclic equivalent), > 60 mg of phenelzine (or its monoamine oxidase inhibitor equivalent), > 20 mg of fluoxetine (or its SSRI-equivalent), > 150mg of bupropion, > 300mg of trazodone (or nefazodone), >75 mg of venlafaxine, >60mg of duloxetine, or > 15mg of mirtazapine. A trial of adequate duration was defined as one during which the patient was on any given antidepressant at an adequate dose for a minimum of 6 weeks.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Massachusetts General Hospital- Depression Clinical and Research Program
Boston, Massachusetts, 02114
About this study
Official title: A Three-phase Study Designed to Test the Efficacy, Tolerability and Safety of the Combination of Ziprasidone With Selective Serotonin Reuptake Inhibitors (SSRI) for Patients With Major Depressive Disorder (MDD) That do Not Sufficiently Respond to Treatment With SSRIs.
The purpose of this study is to see if adding the study drug, ziprasidone, to an antidepressant medication helps improve symptoms of Major Depressive Disorder (MDD). We are studying the drug's effectiveness in treating depression, as well as its safety when it is added to another drug.
Hypothesis A: There will be a difference in the percentage of responders in the two treatment conditions during phase 2; response rates will be higher for the ziprasidone group.
Read the detailed description
The proposed study involves three phases. The first phase is an 8-week, open-label trial of an SSRI for MDD. Patients who do not experience sufficient symptom improvement following this open-label trial will be enrolled in a 6-week, double-blind, placebo controlled trial of ziprasidone augmentation (second phase). Ziprasidone and placebo-remitters will then enter a 12-month, double-blind extension phase (third phase). We estimate that approximately 400 patients will enter phase 1 of the study so that a minimum of 180 subjects will enter double-blind treatment (phase 2) over 5 years. Each treatment arm during phase 2 will have 90 subjects.
Hypothesis B1: During phase 2, there will be a difference between the two groups in the percentage of responders (50% or greater reduction in symptom severity) with regards to anxious symptoms of MDD as measured by the 14-item Hamilton Anxiety Rating Scale (HAM-A); response rates will be higher for the ziprasidone group.
Hypothesis B2: During phase 2, there will be a difference between the two groups in the percentage of responders (50% or greater reduction in symptom severity) with regards to painful symptoms of MDD, as measured by the overall visual analogue pain (VAS-pain) scale scores; response rates will be higher for the ziprasidone group.
Hypothesis C: The time to relapse during phase 3 will be shorter among adjunctive placebo- than ziprasidone-remitters.
- Conditions
- Major Depressive Disorder
- Being tested
- Ziprasidone, Placebo
- Keywords
- Major Depressive Disorder, Major Depression, Depression, Geodon, Ziprasidone, SSRI Augmentation, Treatment Resistant Depression
- Medical subject headings
- Depressive Disorder, Major, Depression, Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZiprasidoneDrug
Also called Geodon
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.
PlaceboDrug
0mg Placebo per day (1-4 tablets per day). "Dose increases" and "dose decreases" may occur, but patient will remain at 0mg placebo.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Patients in group 1 will receive Ziprasidone for the full 8 weeks of Phase 2. If they are in remission following phase two, and decide to enter phase three, they will continue on Ziprasidone for 12 months. Receives: Drug: Ziprasidone |
| 2 | Placebo comparator | Patients in group 2 will receive Placebo for the full 8 weeks of Phase 2. If they are in remission following phase two, and decide to enter phase three, they will continue on Placebo for 12 months. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Primary Outcome Measure Will be Response Rates (50% Decrease in HAM-D-17 Scores) During Phase 2
The primary outcome measure will be response rates (50% decrease in HAM-D-17 scores) during phase 2. A responder will be a patient who experiences a 50% or greater decrease in symptoms according to the HAM-D-17 during phase 2.
Measured: 8 Weeks
Secondary outcomes (2)
Remission Rates (HAM-D 17 Scores of Less Than 8) After Treatment Phase 2.
A secondary outcome measure will be remission rates (HAM-D 17 scores of less than 8) after treatment phase 2.. A remitted will be a patient with a final score of 7 or less on the HAMD-17 during phase 2.
Measured: 8 weeks
Comparing Scores on HAM-D 17 Baseline Visit to Phase 2 Final Visit at Week 8
This will involve looking at the change in HAM-D 17 scores during phase 2. For HAMD-17 the minimum is 0, the maximum is 52, and greater scores represent more symptoms.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2008 (estimated)
- Study startJul 2008
- Primary completionMar 2014
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 458 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of Alabama at Birmingham
- Responsible party
- Principal investigator, George I. Papakostas, Massachusetts General Hospital
- Investigators
- George I Papakostas, M.D., Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00633399
- Sponsor's protocol ID
- 2007-P-002361
- Status last verified
- Jun 2014
- First submitted
- 4 Mar 2008
- Last updated
- 3 Jul 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Mischoulon D, Shelton RC, Baer L, Bobo WV, Curren L, Fava M, Papakostas GI. Ziprasidone Augmentation of Escitalopram for Major Depressive Disorder: Cardiac, Endocrine, Metabolic, and Motoric Effects in a Randomized, Double-Blind, Placebo-Controlled Study. J Clin Psychiatry. 2017 Apr;78(4):449-455. doi: 10.4088/JCP.15m10426.
PubMed 27835715Ionescu DF, Shelton RC, Baer L, Meade KH, Swee MB, Fava M, Papakostas GI. Ziprasidone augmentation for anxious depression. Int Clin Psychopharmacol. 2016 Nov;31(6):341-6. doi: 10.1097/YIC.0000000000000133.
PubMed 27306192Papakostas GI, Fava M, Baer L, Swee MB, Jaeger A, Bobo WV, Shelton RC. Ziprasidone Augmentation of Escitalopram for Major Depressive Disorder: Efficacy Results From a Randomized, Double-Blind, Placebo-Controlled Study. Am J Psychiatry. 2015 Dec;172(12):1251-8. doi: 10.1176/appi.ajp.2015.14101251. Epub 2015 Jun 18.
PubMed 26085041
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Three-phase Study Designed to Test the Efficacy, Tolerability and Safety of the Combination of Ziprasidone With Selective Serotonin Reuptake Inhibitors (SSRI) for Patients With Major Depressive Disorder (MDD) That do Not Sufficiently Respond to Treatment With SSRIs.
- ClinicalTrials.gov ID
- NCT00633399
- Acronym / sponsor ID
- 2007-P-002361
- Conditions
- Major Depressive Disorder
- Keywords
- Major Depressive Disorder, Major Depression, Depression, Geodon, Ziprasidone, SSRI Augmentation, Treatment Resistant Depression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 458 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- University of Alabama at Birmingham
- Study start
- Jul 2008
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 12 Mar 2008 (estimated)
- Results
- Posted 3 Jul 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to see if adding the study drug, ziprasidone, to an antidepressant medication helps improve symptoms of Major Depressive Disorder (MDD). We are studying the drug's effectiveness in treating depression, as well as its safety when it is added to another drug.
Hypothesis A: There will be a difference in the percentage of responders in the two treatment conditions during phase 2; response rates will be higher for the ziprasidone group.
Detailed description
The proposed study involves three phases. The first phase is an 8-week, open-label trial of an SSRI for MDD. Patients who do not experience sufficient symptom improvement following this open-label trial will be enrolled in a 6-week, double-blind, placebo controlled trial of ziprasidone augmentation (second phase). Ziprasidone and placebo-remitters will then enter a 12-month, double-blind extension phase (third phase). We estimate that approximately 400 patients will enter phase 1 of the study so that a minimum of 180 subjects will enter double-blind treatment (phase 2) over 5 years. Each treatment arm during phase 2 will have 90 subjects.
Hypothesis B1: During phase 2, there will be a difference between the two groups in the percentage of responders (50% or greater reduction in symptom severity) with regards to anxious symptoms of MDD as measured by the 14-item Hamilton Anxiety Rating Scale (HAM-A); response rates will be higher for the ziprasidone group.
Hypothesis B2: During phase 2, there will be a difference between the two groups in the percentage of responders (50% or greater reduction in symptom severity) with regards to painful symptoms of MDD, as measured by the overall visual analogue pain (VAS-pain) scale scores; response rates will be higher for the ziprasidone group.
Hypothesis C: The time to relapse during phase 3 will be shorter among adjunctive placebo- than ziprasidone-remitters.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: ZiprasidonePatients in group 1 will receive Ziprasidone for the full 8 weeks of Phase 2. If they are in remission following phase two, and decide to enter phase three, they will continue on Ziprasidone for 12 months. |
| 2 | Placebo comparator | Drug: PlaceboPatients in group 2 will receive Placebo for the full 8 weeks of Phase 2. If they are in remission following phase two, and decide to enter phase three, they will continue on Placebo for 12 months. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Written informed consent.
- Men or women, 18-65 years of age.
- MDD, current, according to DSM-IV criteria and as diagnosed by the SCID- I/P during the screen and baseline visit of phase 1.
- A HAM-D-17 score > 14 during the screen and baseline visit of phase 1.
Key exclusion criteria (11 listed)
- Pregnant women or women of child bearing potential who are not using a medically accepted means of contraception (oral contraceptive or implant, condom, diaphragm, spermicide, intrauterine
- Device, tubal ligation, or partner with vasectomy).
- Serious suicide or homicide risk, as assessed by evaluating clinician.
- Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease or uncontrolled seizure disorder.
- History of multiple adverse drug reactions or allergy to the study drug.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZiprasidoneAlso: Geodon20mg-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. | Drug | 1 |
| Placebo0mg Placebo per day (1-4 tablets per day). "Dose increases" and "dose decreases" may occur, but patient will remain at 0mg placebo. | Drug | 2 |
Primary outcome
The Primary Outcome Measure Will be Response Rates (50% Decrease in HAM-D-17 Scores) During Phase 2
Time frame: 8 Weeks
The primary outcome measure will be response rates (50% decrease in HAM-D-17 scores) during phase 2. A responder will be a patient who experiences a 50% or greater decrease in symptoms according to the HAM-D-17 during phase 2.
2 secondary outcomes
Remission Rates (HAM-D 17 Scores of Less Than 8) After Treatment Phase 2.
Time frame: 8 weeks
Comparing Scores on HAM-D 17 Baseline Visit to Phase 2 Final Visit at Week 8
Time frame: 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27835715Mischoulon D, Shelton RC, Baer L, Bobo WV, Curren L, Fava M, Papakostas GI. Ziprasidone Augmentation of Escitalopram for Major Depressive Disorder: Cardiac, Endocrine, Metabolic, and Motoric Effects in a Randomized, Double-Blind, Placebo-Controlled Study. J Clin Psychiatry. 2017 Apr;78(4):449-455. doi: 10.4088/JCP.15m10426.
- Derived from this study: PubMed 27306192Ionescu DF, Shelton RC, Baer L, Meade KH, Swee MB, Fava M, Papakostas GI. Ziprasidone augmentation for anxious depression. Int Clin Psychopharmacol. 2016 Nov;31(6):341-6. doi: 10.1097/YIC.0000000000000133.
- Derived from this study: PubMed 26085041Papakostas GI, Fava M, Baer L, Swee MB, Jaeger A, Bobo WV, Shelton RC. Ziprasidone Augmentation of Escitalopram for Major Depressive Disorder: Efficacy Results From a Randomized, Double-Blind, Placebo-Controlled Study. Am J Psychiatry. 2015 Dec;172(12):1251-8. doi: 10.1176/appi.ajp.2015.14101251. Epub 2015 Jun 18.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
George I Papakostas, M.D. principal investigator
Massachusetts General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ziprasidone in people with Major Depressive Disorder, run by Massachusetts General Hospital at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Primary Outcome Measure Will be Response Rates (50% Decrease in HAM-D-17 Scores) During Phase 2 (time frame: 8 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00633399, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2014.