Ketamine and Nitroprusside for Depression

This randomized, triple-blind, parallel Phase II trial tests whether sodium nitroprusside alters the antidepressant efficacy or reduces the psychotomimetic effects of ketamine in patients with major depression.

Nitroprusside is administered as a 0.5 µg/kg/min IV infusion over 240 minutes with ketamine 0.5 mg/kg IV given during the final 40 minutes; outcomes include MADRS for mood, CADSS for psychotomimetic effects, and serial blood biomarkers to explore mechanisms.

Participants

Ages

21 – 65

Sexes

Male & Female

BMI

Psychosis History

Inclusion Criteria

Inclusion Criteria:
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

Exclusion Criteria

Exclusion Criteria:
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;
Hepatic injury, as reflected by AST or ALT greater than twice the upper limit of the reference range (AST: >80; ALT >110)
Patients who have a positive urine toxicology for illicit substances at screening and within 24 hours of the infusion;
Treatment with an irreversible MAOI within 2 weeks prior to randomization or fluoxetine within 4 weeks prior to randomization;
Treatment with other antidepressants (classified as SSRIs, SNRIs, Atypical Antidepressants, MAOIs, TCAs) within one week of randomization.
Previous recreational use of phencyclidine (PCP) or KET;
Hypertension with systolic BP >160 mm Hg or diastolic BP >90 mm Hg at screening, systolic BP > 165 mm Hg or diastolic BP > 95 mm Hg immediately prior to treatment with study drug or hypotension with systolic BP < 90 or diastolic < 60 at screening or immediately prior to treatment with study drug; heart rate >110 or <60 at either of these time points;
Treatment with sildenafil (Viagra), tadalafil (Cialis), Avanafil (Stendra), Vardenafil (Levitra) or other drugs in the same category of phosphodiesterase-5 enzyme inhibitors within 2 weeks of infusion.

Company

Product

Legal

Detailed Description

Study Protocol

Preparation

Dosing

Locations

Integration

Study Arms & Interventions

Placebo + Ketamine

Interventions

Nitroprusside + Ketamine

Interventions

Participants

Inclusion Criteria

Exclusion Criteria

Study Details

Study Team

Sponsors & Collaborators