- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01833897
NMDA Antagonists in Bipolar Depression
April 25, 2016 updated by: New York State Psychiatric Institute
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.
Study Overview
Status
Completed
Conditions
Intervention / 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 Type
Interventional
Enrollment (Actual)
8
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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New York
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New York, New York, United States, 10032
- New York State Psychiatric Institute
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 60 years (ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Ketamine and DCS treatment
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.
|
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.
Other Names:
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).
Other Names:
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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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 |
8 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Loss of Motivated Behavior HAM-D Factor
Time Frame: 8 weeks
|
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
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8 weeks
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HAM-D Suicide Item
Time Frame: 8 weeks
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Ham-D suicide item: range 0-4, higher scores indicate worse symptoms
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8 weeks
|
Hamilton Anxiety Scale
Time Frame: 8 weeks
|
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.
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8 weeks
|
Beck's Depression Inventory
Time Frame: 8 weeks
|
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.
|
8 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Joshua T Kantrowitz, MD, New York State Psychiatric Institute
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2013
Primary Completion (ACTUAL)
July 1, 2014
Study Completion (ACTUAL)
March 1, 2016
Study Registration Dates
First Submitted
April 12, 2013
First Submitted That Met QC Criteria
April 16, 2013
First Posted (ESTIMATE)
April 17, 2013
Study Record Updates
Last Update Posted (ESTIMATE)
June 1, 2016
Last Update Submitted That Met QC Criteria
April 25, 2016
Last Verified
March 1, 2016
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Bipolar and Related Disorders
- Bipolar Disorder
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Central Nervous System Depressants
- Autonomic Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anesthetics, Dissociative
- Anesthetics, Intravenous
- Anesthetics, General
- Anesthetics
- Excitatory Amino Acid Antagonists
- Excitatory Amino Acid Agents
- Antimetabolites
- Antiemetics
- Gastrointestinal Agents
- Anti-Bacterial Agents
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Serotonin Uptake Inhibitors
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Serotonin Agents
- Antidepressive Agents
- Cytochrome P-450 Enzyme Inhibitors
- Antidepressive Agents, Second-Generation
- Cytochrome P-450 CYP2D6 Inhibitors
- Antitubercular Agents
- Antibiotics, Antitubercular
- Anti-Infective Agents, Urinary
- Renal Agents
- Ketamine
- Olanzapine
- Quetiapine Fumarate
- Fluoxetine
- Cycloserine
Other Study ID Numbers
- 6535
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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