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Trial record 2 of 17 for:    ketamine bipolar disorder

NMDA Antagonists in Bipolar Depression

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
New York State Psychiatric Institute
ClinicalTrials.gov Identifier:
NCT01833897
First received: April 12, 2013
Last updated: April 25, 2016
Last verified: March 2016
  Purpose
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.

Condition Intervention Phase
Bipolar Disorder
Drug: Standard of Care
Drug: Ketamine
Drug: D-cycloserine
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: NMDA Antagonists in Bipolar Depression

Resource links provided by NLM:


Further study details as provided by New York State Psychiatric Institute:

Primary Outcome Measures:
  • Hamilton Depression Rating Scale (HAM-D) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

    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 [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
    Ham-D suicide item: range 0-4, higher scores indicate worse symptoms

  • Hamilton Anxiety Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 8
Study Start Date: March 2013
Study Completion Date: March 2016
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Standard of Care
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:
  • Quetiapine
  • Olanzapine
  • fluoxetine
Drug: Ketamine
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 Name: Ketamine Hydrochloride
Drug: D-cycloserine
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 Name: DCS

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).
  Eligibility

Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01833897

Locations
United States, New York
New York State Psychiatric Institute
New York, New York, United States, 10032
Sponsors and Collaborators
New York State Psychiatric Institute
Investigators
Principal Investigator: Joshua T Kantrowitz, MD New York State Psychiatric Institute
  More Information

Responsible Party: New York State Psychiatric Institute
ClinicalTrials.gov Identifier: NCT01833897     History of Changes
Other Study ID Numbers: 6535 
Study First Received: April 12, 2013
Results First Received: March 17, 2016
Last Updated: April 25, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by New York State Psychiatric Institute:
Bipolar Disorder

Additional relevant MeSH terms:
Bipolar Disorder
Bipolar and Related Disorders
Mental Disorders
Ketamine
Depression
Behavioral Symptoms
Quetiapine Fumarate
Olanzapine
Fluoxetine
Cycloserine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antipsychotic Agents
Tranquilizing Agents
Psychotropic Drugs
Antiemetics
Autonomic Agents
Gastrointestinal Agents
Serotonin Uptake Inhibitors

ClinicalTrials.gov processed this record on December 09, 2016