Ketamine and Nitroprusside for Depression
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|ClinicalTrials.gov Identifier: NCT03102736|
Recruitment Status : Completed
First Posted : April 6, 2017
Last Update Posted : November 11, 2019
|Condition or disease||Intervention/treatment||Phase|
|Depression||Drug: Placebos Drug: Ketamine Drug: Nitroprusside||Phase 2|
Ketamine is an effective fast-acting therapeutic intervention for patients with treatment refractory depression that is known to have the unwanted effect of inducing temporary psychotomimetic symptoms (i.e., delusions, hallucinations and thought disorganization) in some patients. The precise mechanisms of these psychotropic effects remain to be elucidated, but for several decades the NMDA-type glutamate receptor has been hypothesized to be of central importance. In this vain, recent studies of the antihypertensive agent nitroprusside - which increases the availability of the molecular nitric oxide, a known by-product of NMDA activity - have found evidence for antipsychotic properties both in humans with psychotic illness and healthy subjects given ketamine. Here, the clinical team proposes a study that will build on this work by evaluate the effects of nitroprusside on both the antidepressant and psychotomimetic effects of ketamine given to patients to treat refractory depression. In addition, as an exploratory aim, by collecting serial blood samples from the subjects, as the subjects are administered ketamine and nitroprusside, the clinical team will seek to determine functional markers of therapeutic effect and the mechanisms by which ketamine modulates both mood and psychotic states Research Question: The clinical team will test whether the effects of ketamine (KET) on mood and psychotic states is modified by co-administration with sodium nitroprusside (NP) in patients with depression. Furthermore, the clinical team will evaluate the extent to which the underlying biology of disease states and drug mechanisms can be inferred through analysis of brain-derived molecular material isolated from the peripheral circulation.
Aim I. To test whether co-administration with NP has any impact on the efficacy of KET as an antidepressant.
Aim II: To test the ability of NP to prevent the psychotomimetic effects of KET in patients with depression.
Research Hypothesis I. Patients pre-treated with NP will experience attenuated antidepressant effects (measured by MADRS score) following KET compared to pre-treatment with placebo.
Research Hypothesis II: Patients pre-treated with NP will experience attenuated psychotomimetic effects (e.g., CADSS score) immediately following KET compared to pre-treatment with placebo.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||40 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|Masking Description:||Both participants and research staff (aside from pharmacy) will be blinded|
|Official Title:||Pharmacologic Attenuation of Ketamine Using Nitroprusside|
|Actual Study Start Date :||February 14, 2017|
|Actual Primary Completion Date :||June 12, 2019|
|Actual Study Completion Date :||June 12, 2019|
Placebo Comparator: Placebo and Ketamine
Placebo saline given over 240 minutes + 0.5 mg/kg ketamine given over 40 minutes
0.5 mg/kg ketamine
Experimental: Nitroprusside and Ketamine
0.5 mcg/kg nitroprusside given over 140 min + 0.5 mg/kg ketamine given over 40 min
0.5 mg/kg ketamine
0.5 mcg/kg nitroprusside
- Montgomery-Asberg Depression Rating Scale [ Time Frame: Day 15 ]This is a 10-item instrument used for the evaluation of depressive symptoms in adults and for the assessment of any changes to those symptoms. Each of the 10 items is rated on a scale of 0 to 6, with differing descriptors for each item. These individual item scores are added together to form a total score, which can range between 0 (normal) and 60 (severe depression).
- Clinician-Administered Dissociative States Scale [ Time Frame: +240 minutes (after start of Placebo/Nitroprusside infusion) ]This is used to measure dissociative effects during the infusions. The scale includes 19 questions and 8 observer ratings scored from 0 (not at all) to 4 (extremely). The CADSS measures impairment in body perception, environmental perception, time perception, memory impairment, and feelings of unreality.
- Visual Analog Scale [ Time Frame: +240 minutes (after start of Placebo/Nitroprusside infusion) ]These scales are scored in millimeters from the left-hand side of a 100-mm line to a perpendicular mark made by the patient at a point corresponding to the apparent magnitude of the feeling state. Range: 0 ("not at all") to 100 ("most ever").
- Brief Psychiatric Rating Scale [ Time Frame: +240 minutes (after start of Placebo/Nitroprusside infusion) ]used to assess acute behavioral changes during the infusions. Four key BPRS items for the positive (+) symptoms of psychosis will be used: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content. Three items representing the negative (-) symptoms of psychosis will also be used: blunted affect, emotional withdrawal, and motor retardation.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03102736
|United States, New York|
|Icahn School of Medicine at Mount Sinai|
|New York, New York, United States, 10029|
|Principal Investigator:||James Murrough, MD, PhD||Icahn School of Medicine at Mount Sinai|