NMDA Antagonists in Bipolar Depression

NCT01833897 | Completed Phase 4 Results

• 1 other identifier: 6535
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Bipolar Disorder

Keywords

Bipolar Disorder

Outcome Measures

Primary Outcomes (1)

• 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

  8 weeks

Secondary Outcomes (4)

• Loss of Motivated Behavior HAM-D Factor

  8 weeks

• HAM-D Suicide Item

  8 weeks

• Hamilton Anxiety Scale

  8 weeks

• Beck's Depression Inventory

  8 weeks

Study Arms (1)

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.

Drug: Standard of Care; Drug: Ketamine; Drug: D-cycloserine

Interventions

Standard of Care DRUG

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.

Also known as: Quetiapine, Olanzapine, fluoxetine

Ketamine and DCS treatment

Ketamine DRUG

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).

Also known as: Ketamine Hydrochloride

Ketamine and DCS treatment

D-cycloserine DRUG

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.

Also known as: DCS

Ketamine and DCS treatment

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• New York State Psychiatric Institute: lead

Study Sites (1)

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Bipolar Disorder

Interventions

Standard of Care; Quetiapine Fumarate; Olanzapine; Fluoxetine; Ketamine; Cycloserine

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Dibenzothiazepines; Thiazepines; Thiepins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Propylamines; Amines; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Oxazolidinones; Oxazoles; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins

Limitations and Caveats

Limitations include the small-sample and a non-placebo controlled, open-label design.

Results Point of Contact

• Title: Joshua Kantrowitz
• Organization: New York State Psychiatric Institute

jkantrowitz@nki.rfmh.org

646-774-6738

Study Officials

• Joshua T Kantrowitz, MD

  New York State Psychiatric Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2013
• First Posted: April 17, 2013
• Study Start: March 1, 2013
• Primary Completion: July 1, 2014
• Study Completion: March 1, 2016
• Last Updated: June 1, 2016
• Results First Posted: June 1, 2016

Record last verified: 2016-03

Locations

US (1)