Bipolar DisorderPhase 4NCT01833897
NMDA Antagonists in Bipolar Depression
A Phase 4 study testing Ketamine and D-cycloserine in people with Bipolar Disorder, run by New York State Psychiatric Institute at 1 site in United States.
Trial summary
The purpose of this study is to test whether ketamine and D-cycloserine can be safely and effectively used for the treatment of depression. The investigators hypothesize that ketamine will serve as a rapid acting and safe antidepressant in patients with bipolar depression, and furthermore, that D-cycloserine will… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- Ketamine and D-cycloserine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2013to Mar 2016
- Phase
- Phase 4
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male and female patients with Diagnostic and Statistical Manual, Version 4 (DSM-IV) diagnosis of bipolar disorder I or II, current major depressive episode without psychotic features, 18-60
- Insufficient therapeutic response during the current episode
- Medically stable for study participation
- Judged clinically not to be at significant suicide or violence risk
- Subject is off all psychotropic and other types of drugs likely to interact with glutamate for at least 14 days before starting the study. One exception is chloral hydrate or short acting benzodiazepines for distressing anxiety or insomnia (up to 72 hours prior to each MRI scan). In addition, subjects will be off antipsychotics for 1 month and off fluoxetine for 6 weeks prior to the study.
- Subject is likely to be able to tolerate a medication washout. Only subjects who have failed their current medication regiment will be washed off medications.
Who cannot join
- History of chronic psychosis or drug induced psychosis of any kind
- Current DSM-IV diagnosis of drug abuse/dependence in the last six months. Subjects must have a negative drug screen at baseline.
- Women will be excluded if they are pregnant lactating, or not either surgically-sterile or using appropriate methods of birth control. Women must agree to continue using applicable birth control throughout the trial. All women of child-bearing potential must have a negative urine pregnancy test
- Taking any medication contraindicated with ketamine or DCS (ethionamide, isoniazid)
- History of seizures, renal insufficiency or congestive heart failure
- History of clinically significant violence
Show all 12Show fewer
- History of ketamine abuse/dependence or prior clinically significant adverse reaction to ketamine
- Current alcohol abuse or dependence
- Untreated hypertension
- Clinically abnormal liver function tests (LFTs), thyroid, renal function or anemia
- Metal implants, pacemaker, other metal (e.g. shrapnel or surgical prostheses) or paramagnetic objects contained within the body which may present a risk to the subject or interfere with the MR scan.
- Medicinal patch, unless removed prior to the MR scan
Trial locations and contacts
1 site in 1 country.
United States1 site
New York State Psychiatric Institute
New York, New York, 10032
About this study
The purpose of this study is to test whether ketamine and D-cycloserine can be safely and effectively used for the treatment of depression. The investigators hypothesize that ketamine will serve as a rapid acting and safe antidepressant in patients with bipolar depression, and furthermore, that D-cycloserine will serve as an effective therapy following ketamine treatment.
Read the detailed description
Bipolar disorder affects 2% of the population in the United States and the depressive phase contributes disproportionally to morbidity and mortality. At present, few approved treatments for bipolar depression are available, and have primarily depended on manipulations of brain monoaminergic systems. In contrast, recent studies suggest that the N-methyl-D-aspartate glutamate-receptor (NMDAR) antagonist, ketamine, may provide near-immediate relief for treatment resistant depression. Its utility during long-term treatment, however, is limited by its psychotomimetic potency and the need for repeated IV infusions. D-cycloserine (DCS) is an approved oral antibiotic for tuberculosis drug and a well-studied mixed agonist/antagonist at the NMDAR/glycine binding site. DCS showed preliminary evidence of efficacy in a pilot study. DCS would thus be practical from both a safety and route of administration perspective. The present study will explore the feasibility and safety of DCS for maintenance treatments, as measured by magnetic resonance spectroscopy (MRS).
- Conditions
- Bipolar Disorder
- Being tested
- Standard of Care, Ketamine, D-cycloserine
- Keywords
- Bipolar Disorder
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard of CareDrug
Also called Quetiapine, Olanzapine, fluoxetine
Quetiapine, olanzapine-fluoxetine, and lurasidone are approved treatments for bipolar depression. Quetiapine dosing will follow the product label(Anon), and will be titrated over the first 4 days to the target dose of 300 mg. Olanzapine-fluoxetine dosing will also follow standard guidelines. Lurasidone will be started at 20 mg, and titrated up to 60 mg daily as clinically indicated. Study physicians will use clinical judgment to choose between standard-of care treatments, and have the option to titrate standard-of-care within approved ranges, and to prescribe adjunctive benztropine and benzodiazepines if clinically indicated.
KetamineDrug
Also called Ketamine Hydrochloride
Ketamine administration will be carried out according to the methods as described by previous studies. Subjects will receive ketamine hydrochloride (0.5 mg/kg) intravenously during 40 minutes. This dosage was selected based on previous trials of ketamine for the treatment of refractory depression and bipolar depression. Vital signs (blood pressure, heart rate) will be closely monitored throughout the time of infusion. Subjects will be evaluated for 2 consecutive days during this phase; i.e. treatment days (day 1) and rating days (day 2). Non-responders to ketamine will not proceed into the DCS phase. Response will be a 25% improvement on the Hamilton Depression Rating Scale (HDRS).
D-cycloserineDrug
Also called DCS
Immediately after the ketamine infusion, subjects will begin an eight-week treatment of DCS adjunctive to standard of care. DCS dosing will begin at 250 mg for three days→500mg (2 capsules)/day for 1 week → 750 mg (3 capsules)/day for 1 week → and 1000 mg (4 capsules)/day for the remainder of the study.
| Study group | Role | What they receive |
|---|---|---|
| Ketamine and DCS treatment | Experimental | Standard of Care: Subjects will receive treatment with either quetiapine, olanzapine-fluoxetine, or lurasidone. If after about 2 week, subjects are symptomatic, subjects will receive infusion of ketamine hydrochloride (0.5 mg/kg). After the ketamine phase, subject who show improvement will begin an 8-week treatment of oral D-cycloserine. Receives: Drug: Standard of Care; Drug: Ketamine; Drug: D-cycloserine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hamilton Depression Rating Scale (HAM-D)
Depression rating scale: Range 0-53, higher scores indicate worse depression. 0-7 = Normal 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severe Depression
≥ 23 = Very Severe Depression
Measured: 8 weeks
Secondary outcomes (4)
Loss of Motivated Behavior HAM-D Factor
includes the total of four HAM-D items: (Item 7: Work and activities, Item 12. Somatic symptoms (appetite), Item 14. Genital symptoms (libido), and Item 16. Weight loss). Range 0-11, higher scores indicate worse symptoms
Measured: 8 weeks
HAM-D Suicide Item
Ham-D suicide item: range 0-4, higher scores indicate worse symptoms
Measured: 8 weeks
Hamilton Anxiety Scale
Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indi- cates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.
Measured: 8 weeks
Beck's Depression Inventory
Range 0-63, with higher scores worse. Total score of 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe.
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 posted17 Apr 2013 (estimated)
- Study startMar 2013
- Primary completionJul 2014
- Study completionMar 2016
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.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joshua T Kantrowitz, MD, Principal investigator, New York State Psychiatric Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01833897
- Sponsor's protocol ID
- 6535
- Status last verified
- Mar 2016
- First submitted
- 12 Apr 2013
- Last updated
- 1 Jun 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NMDA Antagonists in Bipolar Depression
- ClinicalTrials.gov ID
- NCT01833897
- Acronym / sponsor ID
- 6535
- Conditions
- Bipolar Disorder
- Keywords
- Bipolar Disorder
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Study start
- Mar 2013
- Primary completion
- Jul 2014 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 17 Apr 2013 (estimated)
- Results
- Posted 1 Jun 2016
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 test whether ketamine and D-cycloserine can be safely and effectively used for the treatment of depression. The investigators hypothesize that ketamine will serve as a rapid acting and safe antidepressant in patients with bipolar depression, and furthermore, that D-cycloserine will serve as an effective therapy following ketamine treatment.
Detailed description
Bipolar disorder affects 2% of the population in the United States and the depressive phase contributes disproportionally to morbidity and mortality. At present, few approved treatments for bipolar depression are available, and have primarily depended on manipulations of brain monoaminergic systems. In contrast, recent studies suggest that the N-methyl-D-aspartate glutamate-receptor (NMDAR) antagonist, ketamine, may provide near-immediate relief for treatment resistant depression. Its utility during long-term treatment, however, is limited by its psychotomimetic potency and the need for repeated IV infusions. D-cycloserine (DCS) is an approved oral antibiotic for tuberculosis drug and a well-studied mixed agonist/antagonist at the NMDAR/glycine binding site. DCS showed preliminary evidence of efficacy in a pilot study. DCS would thus be practical from both a safety and route of administration perspective. The present study will explore the feasibility and safety of DCS for maintenance treatments, as measured by magnetic resonance spectroscopy (MRS).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ketamine and DCS treatment | Experimental | Drug: Standard of Care, Drug: Ketamine, Drug: D-cycloserineStandard of Care: Subjects will receive treatment with either quetiapine, olanzapine-fluoxetine, or lurasidone. If after about 2 week, subjects are symptomatic, subjects will receive infusion of ketamine hydrochloride (0.5 mg/kg). After the ketamine phase, subject who show improvement will begin an 8-week treatment of oral D-cycloserine. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Male and female patients with Diagnostic and Statistical Manual, Version 4 (DSM-IV) diagnosis of bipolar disorder I or II, current major depressive episode without psychotic features, 18-60
- Insufficient therapeutic response during the current episode
- Medically stable for study participation
- Judged clinically not to be at significant suicide or violence risk
- Subject is off all psychotropic and other types of drugs likely to interact with glutamate for at least 14 days before starting the study. One exception is chloral hydrate or short acting benzodiazepines for distressing anxiety or insomnia (up to 72 hours prior to each MRI scan). In addition, subjects will be off antipsychotics for 1 month and off fluoxetine for 6 weeks prior to the study.
Key exclusion criteria (12 listed)
- History of chronic psychosis or drug induced psychosis of any kind
- Current DSM-IV diagnosis of drug abuse/dependence in the last six months. Subjects must have a negative drug screen at baseline.
- Women will be excluded if they are pregnant lactating, or not either surgically-sterile or using appropriate methods of birth control. Women must agree to continue using applicable birth control throughout the trial. All women of child-bearing potential must have a negative urine pregnancy test
- Taking any medication contraindicated with ketamine or DCS (ethionamide, isoniazid)
- History of seizures, renal insufficiency or congestive heart failure
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 |
|---|---|---|
| Standard of CareAlso: Quetiapine, Olanzapine, fluoxetineQuetiapine, olanzapine-fluoxetine, and lurasidone are approved treatments for bipolar depression. Quetiapine dosing will follow the product label(Anon), and will be titrated over the first 4 days to the target dose of 300 mg. Olanzapine-fluoxetine dosing will also follow standard guidelines. Lurasidone will be started at 20 mg, and titrated up to 60 mg daily as clinically indicated. Study physicians will use clinical judgment to choose between standard-of care treatments, and have the option to titrate standard-of-care within approved ranges, and to prescribe adjunctive benztropine and benzodiazepines if clinically indicated. | Drug | Ketamine and DCS treatment |
| KetamineAlso: Ketamine HydrochlorideKetamine administration will be carried out according to the methods as described by previous studies. Subjects will receive ketamine hydrochloride (0.5 mg/kg) intravenously during 40 minutes. This dosage was selected based on previous trials of ketamine for the treatment of refractory depression and bipolar depression. Vital signs (blood pressure, heart rate) will be closely monitored throughout the time of infusion. Subjects will be evaluated for 2 consecutive days during this phase; i.e. treatment days (day 1) and rating days (day 2). Non-responders to ketamine will not proceed into the DCS phase. Response will be a 25% improvement on the Hamilton Depression Rating Scale (HDRS). | Drug | Ketamine and DCS treatment |
| D-cycloserineAlso: DCSImmediately after the ketamine infusion, subjects will begin an eight-week treatment of DCS adjunctive to standard of care. DCS dosing will begin at 250 mg for three days→500mg (2 capsules)/day for 1 week → 750 mg (3 capsules)/day for 1 week → and 1000 mg (4 capsules)/day for the remainder of the study. | Drug | Ketamine and DCS treatment |
Primary outcome
Hamilton Depression Rating Scale (HAM-D)
Time frame: 8 weeks
Depression rating scale: Range 0-53, higher scores indicate worse depression. 0-7 = Normal 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severe Depression ≥ 23 = Very Severe Depression
4 secondary outcomes
Loss of Motivated Behavior HAM-D Factor
Time frame: 8 weeks
HAM-D Suicide Item
Time frame: 8 weeks
Hamilton Anxiety Scale
Time frame: 8 weeks
Beck's Depression Inventory
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 1 Jun 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Joshua T Kantrowitz, MD principal investigator
New York State Psychiatric Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ketamine and D-cycloserine in people with Bipolar Disorder, run by New York State Psychiatric Institute at 1 site 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 6 inclusion and 12 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 1 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 1 Jun 2016). 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?
Hamilton Depression Rating Scale (HAM-D) (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Jun 2016.