Ketamine and Nitroprusside for Depression

NCT03102736 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: GCO 16-1580
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the effects of the medication ketamine and the medication called nitroprusside in patients with major depression. Ketamine has both good and bad effects. Some studies have shown that ketamine improves depression. However, studies have also shown that it causes strange and sometimes unpleasant sensations referred to "psychotic" or "dissociative" symptoms. An example of a psychotic symptom would be hearing or seeing something that in reality is not there. The study team would like to see if nitroprusside can prevent the reported bad effects of ketamine without blocking the reported good effects. This might make ketamine a better treatment for depression.

Conditions

Depression

Keywords

depression; ketamine; nitroprusside

Outcome Measures

Primary Outcomes (1)

• Montgomery-Asberg Depression Rating Scale

  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).

  24 hours after start of infusion

Secondary Outcomes (3)

• Clinician-Administered Dissociative States Scale

  240 minutes after start of infusion

• Visual Analog Scale

  240 minutes after start of infusion

• Brief Psychiatric Rating Scale (BPRS)

  +240 minutes (after start of Placebo/Nitroprusside infusion)

Study Arms (2)

Placebo and Ketamine

PLACEBO COMPARATOR

Placebo saline given over 240 minutes + 0.5 mg/kg ketamine given over 40 minutes

Drug: Placebos; Drug: Ketamine

Nitroprusside and Ketamine

EXPERIMENTAL

0.5 mcg/kg/min nitroprusside given over 240 min (4 hours) - 0.5 mg/kg ketamine given over the last 40 min of the nitroprusside infusion (starting at minute 200 the two drugs are given together)

Drug: Ketamine; Drug: Nitroprusside

Interventions

Placebos DRUG

Placebo saline

Placebo and Ketamine

Ketamine DRUG

0.5 mg/kg ketamine

Nitroprusside and Ketamine; Placebo and Ketamine

Nitroprusside DRUG

0.5 mcg/kg nitroprusside

Nitroprusside and Ketamine

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients, 21-65 years of age;
• Female individuals who are not of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year) or using a medically accepted reliable means of contraception. Women using oral contraceptive medication for birth control must also be using a barrier contraceptive. Women of childbearing potential must also have a negative pregnancy test at screening and at pre-infusion;
• Participants must fulfill current DSM-5 criteria for Major Depression without psychotic features or Persistent Depressive Disorder with specifier of "with persistent major depressive episode";
• Depression is at least moderate severity, defined as a CGI-S score of ≥ 4;
• Current major depressive episode is of at least 4 weeks duration
• Each participant must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document
• Each participant must be able to identify a family member, physician, or friend who will act as an emergency contact

You may not qualify if:

• Lifetime history of psychotic features, diagnosis of schizophrenia or any other psychotic disorder, or diagnosis of bipolar disorder;
• Lifetime histories of autism, mental retardation, pervasive developmental disorders, or Tourette's syndrome;
• Current diagnosis of obsessive compulsive disorder (OCD) or eating disorder (bulimia nervosa or anorexia nervosa);
• Subjects with DSM-V drug or alcohol abuse/dependence within the preceding 2 years;
• Patients with schizotypal or antisocial personality disorder, or any clinically significant axis II disorder that would, in the investigator's judgment, preclude safe study participation;
• Patients judged clinically to be at serious and imminent suicidal or homicidal risk;
• Women who are either pregnant or nursing;
• Any serious, unstable medical illnesses including hepatic, renal impairment, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, or hematologic disease;
• History of congestive heart failure or established coronary artery disease;
• History of cerebrovascular insufficiency
• History of intrapulmonary arteriovenous shunts, co-arctation of the aorta or other conditions where cardiac outflow tract is obstructed;
• Vitamin B12 deficiency;
• Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG;
• Renal impairment, as reflected by a BUN \> 20 mg/dL and/or creatinin clearance of \>1.3 mg/dL;
• Thyroid impairment, as reflected by a thyroid-stimulating hormone (TSH) \> 4.2 mU/L;

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Related Publications (1)

• Bevilacqua L, Charney A, Pierce CR, Richards SM, Jha MK, Glasgow A, Brallier J, Kirkwood K, Bagiella E, Charney DS, Murrough JW. Role of nitric oxide signaling in the antidepressant mechanism of action of ketamine: A randomized controlled trial. J Psychopharmacol. 2021 Feb;35(2):124-127. doi: 10.1177/0269881120985147.

  PMID: 33522376 DERIVED

MeSH Terms

Conditions

Depression

Interventions

Ketamine; Nitroprusside

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Ferricyanides; Cyanides; Anions; Ions; Electrolytes; Inorganic Chemicals; Ferric Compounds; Iron Compounds; Hydrogen Cyanide; Nitrogen Compounds

Results Point of Contact

• Title: Dr. James Murrough
• Organization: Icahn School of Medicine at Mount Sinai

james.murrough@mssm.edu

212-585-1640

Study Officials

• James Murrough, MD, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Both participants and research staff (aside from pharmacy) will be blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: March 31, 2017
• First Posted: April 6, 2017
• Study Start: February 14, 2017
• Primary Completion: June 12, 2019
• Study Completion: June 12, 2019
• Last Updated: July 2, 2020
• Results First Posted: July 2, 2020

Record last verified: 2020-07

Locations

US (1)