Back to resultsNMDA Antagonists in Bipolar Depression
Primary Purpose
Bipolar Disorder
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Standard of Care
Ketamine
D-cycloserine
Sponsored by
About this trial
This is an interventional treatment trial for Bipolar Disorder focused on measuring Bipolar Disorder
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
- 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
Sites / Locations
- New York State Psychiatric Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Ketamine and DCS treatment
Arm Description
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.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
HAM-D Suicide Item
Ham-D suicide item: range 0-4, higher scores indicate worse symptoms
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.
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.
Full Information
NCT ID
NCT01833897
First Posted
April 12, 2013
Last Updated
April 25, 2016
Sponsor
New York State Psychiatric Institute
1. Study Identification
Unique Protocol Identification Number
NCT01833897
Brief Title
NMDA Antagonists in Bipolar Depression
Official Title
NMDA Antagonists in Bipolar Depression
Study Type
Interventional
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
March 2013 (undefined)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
March 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
New York State Psychiatric Institute
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bipolar Disorder
Keywords
Bipolar Disorder
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ketamine and DCS treatment
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Standard of Care
Other Intervention Name(s)
Quetiapine, Olanzapine, fluoxetine
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Ketamine
Other Intervention Name(s)
Ketamine Hydrochloride
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
D-cycloserine
Other Intervention Name(s)
DCS
Intervention Description
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.
Primary Outcome Measure Information:
Title
Hamilton Depression Rating Scale (HAM-D)
Description
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
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Loss of Motivated Behavior HAM-D Factor
Description
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
Time Frame
8 weeks
Title
HAM-D Suicide Item
Description
Ham-D suicide item: range 0-4, higher scores indicate worse symptoms
Time Frame
8 weeks
Title
Hamilton Anxiety Scale
Description
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.
Time Frame
8 weeks
Title
Beck's Depression Inventory
Description
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.
Time Frame
8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joshua T Kantrowitz, MD
Organizational Affiliation
New York State Psychiatric Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
New York State Psychiatric Institute
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
12. IPD Sharing Statement
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NMDA Antagonists in Bipolar Depression
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